Biogen Idec Inc. disclosed three more cases of a rare brain infection in multiple sclerosis patients on Tysabri, which it sells with Elan Corp., bringing the total number of cases to 58 as of July 2.

The Cambridge, Mass., biotech company reported an additional death among patients that have developed progressive multifocal leukoencephalopathy, or PML, bringing the total to 12.

Tysabri is considered a highly effective therapy for MS, and its growth is important to the future of both Elan and Biogen. But its sales have been slower than originally hoped due to concerns about the risk of PML that led to its temporary withdrawal beginning in 2005. The infection re-emerged in mid-2008, and Biogen provides regular updates about the number cases.

The overall global PML rate is about 0.80 per 1,000 patients, the company said, which falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label.

Of the total cases, 22 were in the U.S., 32 were in the European Union and four were in other areas.

The number of cases is important because if the infection rate climbs too high, sales of the drug may drop. A patient's risk of getting PML increases with the number of monthly infusions that he or she receives.

The most recent update translates to a rate of 1.27 cases per 1,000 for patients on the drug for a year or longer, but rises to 1.71 per 1,000 for those on the drug for two years or longer.

Looked at another way, the rate is about 1.42 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.37 case per 1,000 patients in those using it for one to two years, and it is almost nonexistent in patients using it for less than a year.

Elan sets the drug's price, which rose 18.7% in the U.S. on June 30, marking the most aggressive move since the drug's approval in 2004. There have only been two prior price increases: 1.5% a year ago and 8% last December. The price currently stands at $39,988 a year in the U.S.

Source: The Wall Street Journal ©2010 Dow Jones & Company, Inc. (16/07/10)

Recommendation for treatment of progressive multifocal leukoencephalopathy (PML) with Natalizumab #ENS2010

In the name of the Medical Advisory Board of the German Multiple Sclerosis Society (Deutschen Multiple Sklerose Gesellschaft, DMSG), together with the neurological professional associations and in agreement with the Swiss and Austrian MS societies, Prof. Toyka and the board of directors have for the first time issued a recommendation on the use of the MS drug Natalizumab (Tysabri).

The drug was withdrawn from the market in the US in 2005 and then reintroduced the following year. This was because patients contracted progressive multifocal leukoencephalopathy (PML), a serious and formerly often fatal virus infection of the central nervous system with severe neurological complications. The grounds for the recommendation were MS patients treated with Tysabri who then fell ill with PML.

"All doctors treating MS patients with Natalizumab should have PML in mind if new neurological or psychiatric symptoms develop. Our specialists have worked out clear recommendations to ensure the safety of patients. First and foremost, every patient receiving treatment for a period of 24 months must once again be fully informed and monitored at very close intervals, should treatment be continued," says Prof. Toyka.

The German Multiple Sclerosis Society recommends magnetic resonance imaging as a first step in diagnosis. Should this not deliver definitive results, analysis of cerebrospinal fluid to ascertain the presence of the JC virus should be undertaken. Should this prove positive, the German Multiple Sclerosis Society and "Working group Immune Therapy" initiated by Prof. Gold and other colleagues recommends plasmapheresis treatment "so that the active agent is eliminated from the body as quickly as possible."

"Despite the serious and grave risks, we consider there are still no grounds to generally limit treatment with Tysabri strictly to two years," says Prof. Toyka. "The expert group led by Prof. Wiendl is also of this opinion."

Source: Deutschen Multiple Sklerose Gesellschaft, DMSG (22/06/10)

Biogen Idec Inc. disclosed six more cases of a rare brain infection in multiple sclerosis patients on Tysabri, which it sells with Elan Corp. (ELN), bringing the total number of cases to 55 as of June 7.

The Cambridge, Mass., biotech company reported no additional deaths in patients that have developed progressive multifocal leukoencephalopathy, or PML, keeping the total at 11.

Tysabri is considered a highly effective therapy for MS, and its sales growth is important to the future of both Biogen and Elan. But sales have been slower than first anticipated because of concerns about the risk of PML, which led to the drug's 18-month market withdrawal beginning in 2005.

The overall global rate of PML infection is about 0.77 per 1,000 patients, Biogen said, which falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label.

Of the 55 cases Biogen reported, 20 were in the U.S., 32 in the European Union and three in other areas.

Biogen provides monthly updates on the number of PML cases in patients taking Tysabri.

A patient's risk of getting PML increases with the number of monthly infusions that he or she receives, something the Food and Drug Administration highlighted in a January safety update. The agency concluded that the benefits of the medicine continue to outweigh the risks.

The most recent monthly update translates to a rate of 1.24 cases per 1,000 for patients on the drug for a year or longer, but rises to 1.76 per 1,000 for those on the drug at least two years.

The rate of incidence is about 0.35 cases per 1,000 patients on the drug for between one and two years and 1.47 per 1,000 for those taking the drug between two and three years.

Source: MS News Channel.com  (17/06/10)

Biogen Idec and Elan Corporation, plc, in collaboration with EPI-Q, Inc. and Avatar International, LLC, have announced the launch of My MS Health, a first-of-its-kind, web-based, patient-reported outcomes (PRO) research program.

My MS Health is designed to track and provide instant reports on patient function and quality of life (QoL) using validated measures over time. This outcomes research program will assess the impact of using My MS Health on patient-healthcare provider communication, and was developed with guidance from a multidisciplinary steering committee of individuals from healthcare and patient communities, as well as academia.

Interested patients and healthcare providers who meet the research criteria can register for the program at http://www.mymshealth.org.

"My MS Health is a new research tool that may help patients and healthcare providers further communicate about important measures in the management of MS," said Alfred Sandrock, M.D., Ph.D., Senior Vice President of Neurology Research and Development at Biogen Idec. "We believe the patients' perspective on how they feel and function is vital in understanding the overall definition of efficacy in MS therapy."

The user-friendly, secure technology platform and design for My MS Health was developed by EPI-Q, Inc., an industry leader in innovative health economics and outcomes research solutions, and Avatar International, LLC, an industry leader in healthcare measurement and quality improvement. In addition, EPI-Q, Inc. and Avatar International, LLC will implement My MS Health and evaluate data collected via the web-based outcomes research program.

The multidisciplinary steering committee provided critical advice on design and implementation of My MS Health, including the choice and presentation of appropriate measures to ensure relevance to current medical practice and patient needs.

"In developing My MS Health, it was important that all voices - from medicine to academia to the patient community - were heard and that their specific needs were identified and incorporated into the program," said John F. Foley, M.D., director, Rocky Mountain Multiple Sclerosis Clinic, Salt Lake City, and a member of the My MS Health steering committee. "While clinical and radiological assessments play a primary role in patient evaluation, patient-reported outcomes can offer valuable, standardized data that can lead to more comprehensive insights into the physical, neurological and psychological dimensions of a patient's experience."

The pilot phase of My MS Health, anticipated to continue through the first half of 2011, will be available to more than 2,000 patients with relapsing-remitting multiple sclerosis (RRMS) treated with Tysabri® (natalizumab) and to physicians who prescribe the drug in the U.S.

After the pilot phase, there will be a review of intermediate study results to evaluate potential expansion to all people with MS. Interested patients and healthcare providers who meet the study criteria can register for the program at http://www.mymshealth.org.

Source: Medical News Today © 2010 MediLexicon International Ltd (11/06/10)

Tysabri is recommended for the treatment of rapidly evolving severe relapsing remitting MS and for those with highly active relapsing remitting MS who have failed to respond to other treatments.

There are now approximately 67,700 people on Tysabri worldwide and there have been 49 cases of PML to date.

Whilst Tysabri is more effective in treating these more aggressive subtypes of MS, it comes with an increased level of risk for serious side effects including PML - a potentially fatal brain infection. The risk of PML appears to increase with duration of treatment, particularly after two years.

The patient information leaflet has now been revised to include information about the signs of PML and IRIS a severe inflammatory reaction that is likely to occur following treatment for PML.

The updates have also been reflected on the Patient Alert Card which stresses the importance of contacting health professionals if people experience new symptoms, particularly as the signs of PML are very similar to those of MS.

Source: MS Trust (25/05/10)

Biogen Idec Inc. disclosed three more cases of a rare brain infection in multiple sclerosis patients on Tysabri, which it sells with Elan Corp, bringing the total number of cases to 49 as of May 6.

The Cambridge, Mass., biotech company reported no additional deaths in patients that have developed progressive multifocal leukoencephalopathy, or PML, keeping the total at 11.

Tysabri is considered a highly effective therapy for MS, and its growth is important to the future of both Elan and Biogen. But its sales have been slower than originally hoped due to concerns about the risk of PML that led to its temporary withdrawal beginning in 2005.

The overall global rate is about 0.7 per 1,000 patients, the company said, which falls within the 1-in-1,000 rate previously seen in clinical trials and implied on the drug's label.

Of the total cases, 19 were in the U.S., 27 were in the European Union and three were in other areas. Biogen provides monthly updates on the number of PML cases.

The number of cases is important because if the infection rate climbs too high, sales of the drug may drop.

The most recent update translates to a rate of 1.14 cases per 1,000 for patients on the drug for a year or longer, but rises to 1.62 per 1,000 for those on the drug for two years or longer.

A patient's risk of getting PML increases with the number of monthly infusion that he or she receives, something that the Food and Drug administration highlighted in a January safety update. The agency concluded that the benefits of the medicine continue to outweigh the risks.

The rate is about 1.38 cases per 1,000 patients on the drug for between two and three years. The incidence is about 0.32 case per 1,000 patients in those using it for one to two years, and it is almost nonexistent in patients using it for less than a year.

Tysabri's withdrawal from the market occurred after three patients developed PML. The infection re-emerged in mid-2008, and Biogen provided regular updates about the cases until mid-2009. The company began providing monthly updates in mid-February.

Source: Dow Jones Newswires (c) 2010 Dow Jones & Company, Inc (15/05/10)

Biogen has reported two more deaths from PML in Tysabri patients over the past month.

The company said that, as of April 6, 46 cases of PML were reported, eventually leading to 11 deaths.

Source: StreetInsider.com © Copyright 2010 StreetInsider.com (16/04/10)

If multiple sclerosis patients are taken off treatment with natalizumab (Tysabri), their doctors should have a 'Plan B' therapy to prevent relapses and other sequelae, researchers said here.

In reviewing the latest reports on treatment with natalizumab, John Corboy, MD, professor of neurology at the University of Colorado School of Medicine in Denver, noted that one small study from researchers in Texas (Stuve, et al Neurology 2009; 72: 396-401) showed few ill effects as a result of stopping natalizumab.

"They seem to be just fine," Corboy said, "but all these patients were put on interferon or other things."

However, he noted that researchers in Boston observed that if patients are not put on interferon regimens, a significant number on a so-called drug holiday began to show MRI lesions and started having relapses after about 60 to 90 days.

"So if you are going to take someone off natalizumab, you probably should have a plan to substitute something else in order to avoid so-called immune reconstitution inflammatory syndrome and relapses," Corboy said in his presentation at the annual meeting of the American Academy of Neurology.

The main reason for discontinuing natalizumab, he said, is concern about development of life-threatening progressive multifocal leukoencephalopathy (PML). A lingering concern remains that putting patients on an alternative therapy may not mitigate the risk of PML and allow for recovery of immune surveillance.

"As of March 9 there have been 42 confirmed cases of PML among patients exposed to natalizumab. There has been one case of PML that occurred with less than one year's use of natalizumab. All the other cases occurred with more than a year's use," Corboy said. "Strangely, while most of the use of natalizumab is in the U.S., most of the cases are in Europe for reasons that are not clear."

He said about 58% of the use of natalizumab is in the U.S., but about 70% of the cases of PML have occurred among European patients. Full information on all the patients is not known, but 11 of these individuals have died, he said.

"It may have to do with higher exposure to JC virus or they may have something different about their uses of immunosuppressants. All the patients who had serologies done ahead of time were positive for JC virus prior to starting natalizumab," Corboy said.

The JC virus -- formerly known as papovavirus -- was discovered in 1971 and named after the two initials of a patient with PML. The virus causes PML and other diseases in cases of immunodeficiency.

Corboy suggested that knowing JC virus status would allow clinicians to stratify natalizumab therapy -- perhaps stopping after a year for those patients positive for the virus and continuing longer for virus-negative patients. "There hopefully is going to be a serology test available this year" that will help clinicians determine patients' JC virus status, he said.

He noted that PML risk increases over time. Only one case in 60,000 occurs in the first year, but then cases increase to less than one in 1,000 as infusions increase, he said.

Other complications seen among patients on natalizumab include toxoplasmosis. In addition, two patients have been reported with primary central nervous system lymphoma; whether that is specifically linked to natalizumab is not clear.

Lily Jung, MD, medical director of the neurology clinic and chief of neurology at Swedish Medical Center, Seattle, said that if doctors want to stop natalizumab because of concern over risk of PML, a backup plan is necessary.

"If you look at why patients are started on natalizumab, it is because the first-line disease-modifying therapy has failed or the patients have such aggressive disease that the clinician thinks the benefits of natalizumab outweigh the risks," she told MedPage Today.

"If you stop natalizumab because of fear of PML -- and the risk is debated among neurologists -- you still have to treat the multiple sclerosis."

Jung said that clinicians and patients are caught in a bind because in aggressive disease there are not many viable choices, and there are no guarantees that drugs in the pipeline are going to be any safer than current medications.

Corboy disclosed financial relationships with Orasi, Novartis, Lilly, Peptimmune and Genentech.

Jung reported no financial disclosures.

Primary source: American Academy of Neurology
Source reference:
"2FC.002 Neurology Update I, April 11, 2010" AAN 2010; pp. 132-35.

Source: Medpage Today © 2004-2010 MedPage Today, LLC. (13/04/10)

Federal regulators have cited Biogen Idec, Inc. for attempting to downplay the risks of a rare, but often fatal, brain infection that has been linked to the multiple sclerosis drug Tysabri.

The FDA sent a warning letter to the company,  accusing the company of misleading statements made in a series of webcasts used to promote Tysabri. According to the FDA, Biogen aired the webcast eight times between late October and early November of 2009.

In the webcasts, the FDA says Biogen played down the risk of contracting progressive mutifocal luekoencephalopathy (PML), which is a serious infection in the brain that can be caused by side effects of Tysabri. In addition, the FDA said that the webcasts failed to inform the viewer of Tysabri’s approved uses.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat MS and Crohn’s Disease. Manufactured by Biogen Idec Inc. and marketed with Elan Corp PLC, Tysabri has been shown to prevent relapse, cognitive decline and vision loss associated with MS. Sales of Tysabri bring in about $1 billion annually.

A Tysabri recall was issued in 2005 after three users developed the rare and life-threatening brain infection, which attacks the central nervous system, damaging and inflaming the white matter areas of the brain. The drug was reintroduced in July 2006 with stronger warnings about the potential risk of a PML brain infection from Tysabri and the drug was only made available under strict usage guidelines.

PML is believed to be caused by the common JC virus, and Tysabri may reduce the ability of the immune system to combat the virus. There have been 42 cases of Tysabri brain infections since the drug was reintroduced.

In February, the FDA issued a Tysabri PML warning saying that it now appears that the risk of developing PML increases with the number of Tysabri infusions patients receive.

“We are particularly concerned with this webcast because it presents numerous statements that seriously minimize the risk of PML,” the FDA said in its warning letter. “This presentation misleadingly implies that Tysabri patients who developed PML and received treatment…experienced lessened effects of PML and that patient outcomes will necessarily be improved if Tysabri treatment is stopped at the first sign of PML; this has not been established.”

The FDA said that, in truth, no one knows if early detection of PML or discontinuing use of Tysabri once it’s been detected will mitigate the disease. The FDA also points out that there is no evidence that plasma exchanges, a treatment touted in the webcasts, have any benefit in treating PML or other opportunistic infections.

Source: Zikkir © 2009 ZIKKIR WORLD (09/04/10)

Biogen Idec Inc. disclosed seven more cases of a rare brain infection in multiple sclerosis patients using Tysabri, which it sells with Elan Corp, bringing the total number of cases to 42 as of last Wednesday.

Another patient with the infection has died, bringing the total deaths to nine in patients that have developed progressive multifocal leukoencephalopathy, or PML, according to the Cambridge, Mass., biotech company.

Tysabri is considered a highly effective therapy for MS, and its growth is important to the future of both Elan and Biogen. But its sales have been slower than originally hoped because of concerns about the risk of PML, concerns that led to its 18-month market withdrawal beginning in 2005.

Of the total number of cases, 15 were in the U.S., 24 were in the European Union and three were in other areas. Biogen gave its last update in mid-February.

In January, the Food and Drug administration provided a safety update that noted an increased risk of getting PML as the number of infusions of the medicine increase. The agency concluded that the benefits of the medicine continue to outweigh the risks.

The number of cases is important because if the infection rate climbs too high, sales of the drug may drop.

Tysabri's withdrawal from the market occurred after three patients developed PML. The infection re-emerged in mid-2008, and Biogen provided regular updates about the cases until mid-2009. The company began providing monthly updates last month.

Source: Nasdaq Copywrite The Nasdaq Stock Market, Inc.(18/03/10)

Biogen Idec Inc. disclosed four more cases of a rare brain infection in multiple sclerosis patients on Tysabri, which it sells with Elan Corp., bringing the total number of cases to 35.

The number of deaths remains at eight with patients that have developed progressive multifocal leukoencephalopathy, or PML, according to the Cambridge, Mass., biotech company.

Tysabri is considered a highly effective therapy for MS, and its growth is important to the future of both Elan and Biogen. But its sales have been slower than originally hoped amid concerns about
the risk of PML that led to its 18-month market withdrawal beginning in 2005.

“The overall rate is about the same,” said Biogen spokeswoman Naomi Aoki. “It remains consistent with what is outlined in our label.”

Of the new cases, 11 were in the U.S., 21 were in the European Union and three were in other areas.

The last update came from the FDA, which cited 31 cases as of Jan. 21, in a recent safety update noting that MS patients using the drug had increased risk of getting PML as the number of infusions of the medicine increase.

Despite the risk, the agency said the benefits of the medicine continue to outweigh the risks.

The most recent update translates to about 1.56 cases per 1,000 patients on the drug for between two and three years.

The number of cases is important because if the infection rate climbs too high, sales of the drug may drop.

Tysabri’s withdrawal from the market occurred after three patients developed PML. The infection re-emerged in mid-2008, and Biogen provided regular updates about the cases until mid-2009. The company is now providing monthly updates.

Source USHour.com © 2009 Dow Jones Newswires

In the latest blow to the controversial multiple sclerosis drug Tysabri, the U.S. Food and Drug Administration announced that it was slapping a new warning on the drug's label.

In an advisory sent to health-care professionals and patients, the FDA warned that the risk of developing progressive multifocal leukoencephalopathy (PML), a rare but deadly brain infection, increases as more infusions are received.

"This is updated information, taking new cases into account," explained Dr. William Sheremata, professor emeritus of neurology at the University of Miami Miller School of Medicine, who gave the drug to the first humans.

European patients account for most of the new cases and many of them might have been taking multiple drugs, raising their risk for PML, he added.

"This is not new information. We've had this information for a couple of months now [but] the labeling in the past did not make a distinction between the time frames that people were on the drugs," said Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society. "The risk-benefit ratio continues to be about the same as we anticipated since the time the drug was brought back on the market."

Another expert agreed that the clinical picture hasn't been altered by the new label warning.

"I think as long as the medication is being prescribed for the appropriate patient with MS, then the new information we have today is not going to alter medication management," said Dr. Jeffrey Tramonte, director of neurology at the Scott & White University Medical Campus in Round Rock, Texas. "Right now, Tysabri is the most efficacious drug that's ever been approved for the treatment of relapsing-remitting MS, which represents 85 percent of all patients out there who have MS," he said.

"However, it also carries the single most dangerous risk factor, and that's PML," added Tramonte, who only gives Tysabri if his patients have failed or have severe side effects from conventional immunomodulating drugs.

Natalizumab (Tysabri) first received FDA approval in November 2004, only to be pulled from the market three months later after several patients in clinical trials developed PML.

In June 2006, the FDA allowed the drug back on the market, but with strict conditions. According to those revised guidelines, Tysabri can only be administered by approved doctors, at infusion sites and at pharmacies that register and comply with a patient-safety program called CD Touch, designed by drugmaker Biogen Idec and approved by the FDA.

The FDA said the new action was based on reports of 31 confirmed cases of PML as of Jan. 21, 2010.

Information on the risk will also be included in the patient Medication Guide.

However, the FDA did not suggest discontinuing the drug, stating that it "believes that the clinical benefits of Tysabri continue to outweigh the potential risks."

The drug was approved to treat Crohn's disease in early 2008. It is also linked with liver damage. Patients do take the drug long-term, Richert said.

Source: HealthDay © 2010 HealthDay. (06/02/10)

Last week, the European Medicines Agency (EMEA) finalized a review of Biogen Idec’s Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML) associated with the prolonged use of the drug. PML is a rare brain infection caused by the JC virus.

The agency’s Committee for Medicinal Products for Human Use (CHMP) arrived at the conclusion that the risk of a patient developing PML increases after having taken the drug for two years or more, though the risk remains low. However, the benefits of the drug outweigh its risks.

Given the importance of the early detection of PML, the committee has recommended certain measures to ensure that patients and doctors are aware of the associated risks. Measures include updating product information to include the high risk of developing PML after two years of treatment and advice regarding management of patients showing symptoms of PML. In addition, the committee suggested that forms should be signed by patients at the beginning and after two years of treatment after having discussed the risks with their doctors.

The CHMP had to review the drug after 23 confirmed cases of PML were reported between July 2008 and October 2009, causing four deaths. Fourteen of these cases including one death were reported in the EU. Subsequently, the European Commission in October 2009 requested CHMP’s opinion for Tysabri.

As of January 20, 2010, the total number of PML cases has risen to 31, of which 23 were patients who had been receiving the drug for more than two years. This is equivalent to approximately one case of PML for every 1,000 patients treated with Tysabri for two years or more, consistent with the risk mentioned in the Tysabri’s label.

Tysabri, meant for the treatment of multiple sclerosis (MS) is jointly marketed with Elan Corp. The drug was withdrawn from the U.S. market in 2005 due to the PML concern, but was launched again after one year with a strict warning regarding the occurrence of PML.

Source: Yahoo! Finance © 2010 Yahoo! (27/01/10)

The maker of Tysabri will once again provide monthly updates regarding new cases of progressive multifocal leukoencephalopathy, or PML, an often fatal brain infection seen in some people treated with the multiple sclerosis (MS) drug. Biogen Idec Inc. had stopped providing the monthly PML updates last summer.

Tysabri is seen as one of the most effective MS treatments on the market, especially for those with severe cases who have few other options. Unfortunately, it also poses serious risks because of its association with PML. PML attacks the brain and central nervous system and is usually fatal. It is caused by a polyomavirus, called the JC virus. The JC virus is often acquired during childhood. Most adults have been infected with the JC virus but do not develop PML. The virus appears to remain inactive until something (such as a weakened immune system) allows it to be reactivated and start to multiply. Symptoms include vision problems, loss of coordination, and memory loss. Patients who survive the disease are often permanently disabled.

In the U.S. Tysabri was taken off the market in 2005 after three patients in clinical trials developed PML. But the drug was reapproved in 2006, although it was subject to restrictions. Tysabri is now available only to patients with relapsing MS or Crohn’s Disease who are enrolled in the risk minimization plan called the TOUCH Prescribing Program. Under the TOUCH Prescribing Program, every Tysabri-treated patient is closely monitored and followed for the occurrence of PML and other serious opportunistic infections.

In September, the U.S. Food & Drug Administration (FDA) revealed that 24 cases of PML had been reported in Tysabri users, more than double the 11 Biogen Idec had disclosed at its final monthly update in July. As of mid-January, the number of PML cases among people treated with Tysabri stands at 31.

According to The Wall Street Journal, through the new Tysabri monitoring program, Biogen Idec will update physicians about new PML cases at the middle of each month. Doctors will be able to access this information through a password-protected Web site. In addition to the number of PML cases, Biogen Idec will provide details on duration of use, as well as a cumulative patient exposure figure. Investors will be able to access the same information via Investor Relations.

According to the Journal, no public Web site will be launched to provide the information. Tysabri patients can request the information, but the information they will be provided will not be as detailed as what doctors, or even investors, are give. The disparity is the result of regulations that restrict direct interactions between patients and drug companies.

Source: newsinferno.com © 2009 NEWSINFERNO.COM (26/01/10)

The European Medicines Agency has finalised a review of Tysabri (natalizumab) and the risk of progressive multifocal leukoencephalopathy (PML), a rare brain infection caused by the JC virus.

The Agency’s Committee for Medicinal Products for Human Use (CHMP) has concluded that the risk of developing PML increases after two years of use of Tysabri although this risk remains low. However, the benefits of the medicine continue to outweigh its risks for patients with highly active relapsing-remitting multiple sclerosis, for whom there are few treatment options available.

Because it is important that PML is detected early, the Committee recommended that a number of measures be put in place to ensure that patients and doctors are fully aware of the risks of PML. These include:

* An update of the product information to add information about the increase in the risk of PML after two years of treatment and additional advice on how to manage patients who show signs of PML;

* Forms to be signed by patients at the beginning of treatment with Tysabri, and again after two years of treatment, after in-depth discussions about the risk of PML with their doctor.

Measures to minimise the risk of PML were part of the initial marketing authorisation for Tysabri, issued in June 2006. Since then, they have been continuously updated and strengthened to increase awareness of the risk of PML.

The new measures are designed to complement the existing recommendations that patients, and their carers, partners and families should be made aware of the symptoms of PML and that patients should be closely monitored throughout treatment.

Source: EMA (22/01/10)

Biogen Idec officials said Wednesday three more patients have contracted a rare brain infection associated with the company’s multiple sclerosis drug, Tysabri.

However, the Cambridge-based biotechnology company says the additional cases do not impact the overall safety profile for the medication.

The total number of cases of progressive multifocal leukoencephalopathy, or PML, since July 2008 now stands at 31.

More than 60,000 patients have taken Tysabri since the drug’s reintroduction in July 2006, and the incidence of PML is currently .47 cases per 1,000 patients. Tysabri’s warning labels said the anticipated incidence rate of PML is 1 in 1,000 rate.

The company took Tysabri off the market between February 2005 and July 2006 because of concerns about the risk of PML.

Since the risks of contracting PML increases the longer a patient takes the drug, the number of PML cases is expected to rise. So far, 19 cases have been detected in Europe, 10 cases in the United States. Two other cases have been detected elsewhere, according to Biogen officials.

Source: Boston Business Journal © 2010 American City Business Journals, Inc (21/01/10)

Biogen Idec Inc. said sales of its multiple sclerosis drug Tysabri topped $1 billion in 2009, and there were 30 percent more new patients taking the drug.

The growth comes as the rate of a potentially fatal side effect in patients taking Tysabri remains a lingering concern for Wall Street. In 2005, the drug was pulled from the market because of concerns over a potentially fatal brain infection called progressive multifocal leukoencephalopathy, or PML.

Sales resumed in July 2006 with restrictions, though about two dozen cases have since been reported, mainly abroad.

In 2009, sales reached $1.06 billion, with $508.5 million in the U.S. and $550.7 million internationally.

A key concern has been that fears of the brain infection could bog down the addition of new patients. At the end of 2009, there were 48,800 patients taking Tysabri worldwide, including 24,500 in the U.S. and 23,700 internationally. An additional 600 patients were taking the drug in clinical trials.

Several analysts said the rate of new patients adding the drug is slowing.

Leerink Swann analyst Dr. Joshua Schimmer said about 2,600 started taking the drug during the fourth quarter, down from more than 2,900 in the third quarter. But he said much of the concern is already included in outlooks for the company.

He reaffirmed an "Outperform" rating on the stock and said Tysabri revenue is in line with Wall Street expectations.

Looking ahead, the company has said it will focus on accelerating growth of Tysabri and its top seller, the multiple sclerosis drug Avonex.

Source: San Francisco Examiner copyright SF Newspaper Company 2010 (13/01/10)

At least one more patient has been diagnosed with a rare, and potentially fatal brain infection after taking natalizumab (Tysabri), the hit drug for multiple sclerosis from Biogen Idec and Elan, according to Biogen CEO James Mullen.

There are now 28 confirmed cases of patients with progressive multifocal leukoencephalopathy (PML) as of the last count in mid-December. That’s one more case than counted in a detailed summary of PML risk that we published on November 19.

Biogen Idec says it plans to offer monthly updates to physicians about the latest statistics on PML cases, and infection rates. It will also staff a hotline for physicians who want to gather detailed, updated information and context from the company’s medical staff. The company plans to lay out the numbers in a more detailed fashion, with rates on incidence of infection, numbers showing how long certain groups of patients have been on the drug, combined with data on how many total patients are receiving treatment. “That’s the best way for people to visualize what’s going on,” Mullen says.

“The whole communications strategy around that has been challenging,” Mullen said. “We’ve gotten lots of feedback. Pretty much whatever we’ve done, someone won’t like it.”

Source: XCONOMY Boston © 2007-2009, Xconomy, Inc.(07/01/10)

Best-practice recommendations for the selection and management of patients with multiple sclerosis (MS) who may benefit from, or are receiving treatment with Tysabri® (natalizumab) were published today in a supplement to the medical journal Multiple Sclerosis.

The panel provided recommendations focusing on appropriate patient selection and patient management. The recommendations, which recognize the significant efficacy of Tysabri and the need to adequately treat patients who exhibit continued disease activity, are based on U.S. prescribing information and the panel's vast clinical experience in treating MS patients with Tysabri. Recommendations not only take into account the need to adequately treat patients who exhibit continued disease activity, but also the need to weigh the treatment's benefit with potential risks.

"These best-practice approaches have been developed to ensure appropriate use of this highly-effective therapy, especially with MS patients who present with continued disease activity," said Patricia K. Coyle, MD, professor and acting chair, department of neurology, Stony Brook University Medical Center and, director, Stony Brook MS Comprehensive Care Center, Stony Brook, New York. "The benefits of Tysabri are evident in that it can significantly reduce relapse rates, improve cognitive and physical disability and provide freedom from disease activity for many patients, when measured by clinical and radiological measures."

One of the expert panel's recommendations encourages earlier and more rapid transition from first-line treatment to Tysabri. The recommendations also seek to lower the threshold with physicians for treating unacceptable disease activity seen in their patients. According to the panel, factors such as the nature and frequency of relapses, the location of new or unresolved MRI lesions, MRI activity in the spinal cord, rapid or persistent changes in physical disability and functional deficits in cognition should be evaluated and weighed when determining the appropriate patients to treat with Tysabri.

The panel developing the recommendations, which was selected by Biogen Idec, included U.S. academic and community neurologists who, combined, have approximately 2,000 patient-years experience with TYSABRI. The panel members were: Dr. Coyle; John F. Foley, MD, director, Rocky Mountain MS Clinic, Rocky Mountain Neurological Associates; Edward Fox, MD, director, MS Clinic of Central Texas, and clinical assistant professor, University of Texas Medical Branch; Douglas R. Jeffery, MD, PhD, associate professor, department of neurology, Wake Forest University Baptist Medical Center; Frederick E. Munschauer III, MD, professor and chairman, department of neurology, State University of New York at Buffalo, and chief, The Jacobs Neurological Institute; and Carlo Tornatore, MD, associate professor, department of neurology, and director, Multiple Sclerosis Center, Georgetown University Medical Center.

The paper entitled "Best Practice Recommendations for the Selection and Management of Patients with MS Receiving Natalizumab Therapy" is one of four articles that are part of a supplement being published in the journal Multiple Sclerosis. The other papers are "Introduction to Best Practice Recommendations for the Selection and Management of Patients with MS on Natalizumab," "Clinical Efficacy and Benefit of Natalizumab" and "Clinical Vigilance for PML in the Context of Natalizumab." The supplement was funded by Biogen Idec and Elan Corporation, plc.

Source: Eureka Alert! (30/11/09)

It was confirmed yesterday, 18/11/09, by a Biogen Idec spokesperson that there had been a further 3 reported cases of progressive multifocal encephalopathy (PML) in patients taking the multiple sclerosis drug Tysabri. It was also confirmed that one further patient has died of the serious brain infection.

To date 63,000 patients have taken Tysabri since it was returned to the market in July 2006, of which 27 have developed PML and 5 of these have died. Based on these evolving figures, the FDA updated the Tysabri prescribing information earlier this month to say that the risk appears to increase as patients stay on the drug for longer periods of time.

Questions are being asked as to what is happening to those patients who get PML, but survive. Biogen confirmed that it isn’t releasing a patient-by-patient breakdown of what is happening to the survivors, but its medical affairs staff is answering those questions from doctors.

It is reported by Biogen that some of the patients are severely disabled, but a few of the 27 cases have recovered and some have even returned to work.

Commenting on this latest report, Helen Yates, Multiple Sclerosis Resource Centre Chief Executive said, “It is always distressing and worrying to hear of further cases of PML in patients that have been receiving Tysabri.  It is even more of a concern to hear that one of the patients has died as a result of PML when the monitoring process is supposed to alert the medical professionals to the possibility of PML much earlier than previously. 

We keep being told that PML is becoming more treatable and yet Biogen are not releasing information clearly to the people who are considering this treatment thus leaving them unsure as to the genuine risk they are facing.  Tysabri is, without doubt, proving extremely effective for many people but nevertheless patients should be provided with all relevant information when weighing up the risk against efficacy of this drug”

Three drug makers are forming a consortium solely dedicated to researching cases of a rare but potentially deadly brain infection linked to users of their immunosuppressive medications.

The companies are going to focus on studying progressive multifocal leukoencephalopathy (PML), a condition which is increasingly found in patients taking Biogen and Elan’s multiple sclerosis and Crohn’s disease treatment Tysabri, the arthritis disease drug Rituxan by Biogen and Roche, and Raptiva, the psoriasis medication made by Roche unit Genentech.

PML is most often found in people taking Tysabri. There have been 24 cases of the infection in users of the drug, which was pulled from the market in 2006 soon after its launch because of reports of PML in users. The drug was later allowed back in circulation with a stronger warning label added.

The infection is triggered by the JC virus, which most people carry without ever suffering any adverse effects. In some people, however, the virus attacks the central nervous system, leading to decreases in neurologic function and death.

By lowering the body’s immune system to treat multiple sclerosis and prevent flare ups of arthritis and psoriasis, Tysabri, Raptiva and Rituxan leave patients far more vulnerable to PML and other types of opportunistic infections.

PML Research Consortium Planned
The companies’ plan to jointly research PML cases in patients taking their drugs was announced this week at a meeting covering various aspects of the infection at the New York Academy of Sciences, according to a report in The Wall Street Journal.

As part of the consortium, a global database of reported PML cases will be established to help predict, prevent, and treat the infections, officials said. There is concern that the number of PML cases worldwide is under reported due to physicians not linking it to use of the immunosuppressive drugs.

Source Attorneyatlaw © Attorneyatlaw 2009 (12/11/09)

ELAN HAS updated the label on its breakthrough multiple sclerosis (MS) drug Tysabri to reflect the increased risk of patients contracting a serious brain disease if they are on the drug for more than two years.

The company announced last night that, effective immediately, it was updating the label on the drug in the US market following consultation with the US regulator, the Food and Drug Administration (FDA).

The FDA is expected to confirm the move on its own website in the coming days.

The company and its US partner, Biogen Idec, had come under pressure when the European Medicines Agency (EMEA) announced recently that it was opening a review of the risks and benefits of the drug after 24 people had contracted the rare and potentially fatal brain disease progressive multifocal leukoencephalopathy (PML). Four of those patients had died subsequently, the EMEA said.

The news came as a shock. Just a week earlier, the FDA had stated that, as of September 8th, there were just 13 known cases of the disease in Tysabri patients.

Last night Elan and Biogen updated the patient medication guide and the prescriber information guide on the drug’s website to reflect the new label.

A spokeswoman for the company said there was no other change in the wording of the label. In particular, the guidance of a one-in-1,000 risk of contracting PML is unchanged.

Both companies have indicated that talks with the FDA are ongoing as more information about the drug emerges.

The EMEA review is continuing separately. Elan said last night it expected a similar change of wording would be approved in talks with the European regulator.

Source: The Irish Times © 2009 Irishtimes.com (07/11/09)

According to information released yesterday by Biogen Idec, there have been 24 confirmed cases of progressive multifocal leukoencephalopathy (PML, a viral infection of the brain that usually leads to death or severe disability) among people who have used Tysabri® (natalizumab, Biogen Idec and Elan Pharmaceuticals) after it became available for prescription in July 2006.

As of the end of September 2009, 60,700 people have used Tysabri worldwide. Although the absolute risk for PML in patients treated with Tysabri cannot be precisely determined, the sponsor has now released data suggesting that the risk increases with increasing time on therapy, starting out lower than the one-in-one thousand level that was estimated at the time of Tysabri’s re-approval in 2006, and rising after two years of infusions to about one in one thousand. There is insufficient information to determine the risk of PML in those who have been on therapy for three years or more. Right now only 2,000 people have been on the therapy for over three years.

This release followed an October 23 announcement from the EMEA, the European equivalent of the U.S. FDA, indicating that one of its advisory committees was launching a review of the risks and benefits of Tysabri in light of the increasing number of new cases of PML.

Signs of PML: Typical symptoms associated with PML progress quickly over days to weeks, and can include:
• personality or behavioural changes
• changes in thinking, memory, and orientation leading to confusion
• onset of seizures, clumsiness or progressive weakness on one side of the body
• disturbances of vision

If individuals taking Tysabri experience new, unusual symptoms, they should contact their prescribing physician immediately.

Physicians who need guidelines on the protocol to follow when they have a patient on Tysabri who experiences unusual symptoms should contact Biogen Idec.

Details of Cases: According to the company, the 24 cases of PML have occurred in both men and women who had been given infusions of Tysabri every four weeks for a duration ranging from one year to three and a half years, with an average of two years.

16 of the cases occurred in Europe, and 8 in the United States 4 of the 24 died The degree of disability in the 20 survivors is a wide spectrum: at the milder end, some have recovered enough to return to work, and at the other extreme, some are confined to bed, requiring extensive assistance with activities of daily living, and others were in between this range. Further details of their condition were not provided. It appears that when PML is detected and treated early, it generally improves outcomes.

It is important that individuals taking this drug and their doctors be vigilant in monitoring for any occurrence of new, unusual symptoms that might indicate PML.

Based on these cases, the sponsor stressed that, contrary to prior information, the presence of gadolinium-enhancing lesions on MRI does not exclude the possibility of PML. Likewise, the absence of JC virus DNA in the spinal fluid does not exclude PML.

There has been no characteristic among those who have developed PML that would give substantial clues to who might be more likely to develop it, except that half of the cases had prior histories of having been on immunosuppresive therapies, such as mitoxantrone, and less commonly, azathioprine and methotrexate. Right now there is no test that can predict who is more likely at risk for developing PML while using Tysabri; in a large company-sponsored study, testing of blood cells, plasma, serum and urine for the causative JC virus in people before and after 48 weeks of Tysabri therapy (Rudick et al, ECTRIMS 2009) did not show any differences in the presence of the virus in those fluids.

The results of these studies, performed at the U.S. National Instituties of Health, differ somewhat from an earlier study (N. Engl. J. Med. 361:1067, 2009) suggesting higher virus levels after treatment. When PML was suspected, Tysabri infusions were halted.

There is no specific therapy to treat PML, but the best hope is to reconstitute a person’s immune responses. In most of the 24 cases, once PML was confirmed, Tysabri was removed from their systems with the blood-cleansing treatments of either plasma exchange or immunoadsorption. During the aftermath of PML, as the immune system begins to recover, a condition called IRIS (immune reconstitution inflammatory syndrome) usually occurs about 4 weeks after the removal of Tysabri from the system.

The sponsors suggested that some of the treating physicians found that prompt use of intravenous steroids to treat this brain inflammation led to improvement.

Source: US National MS Society (30/10/09)

European regulators reported another case of potentially deadly brain infection in patients taking multiple sclerosis drug Tysabri, taking the worldwide total since 2006 to 24.

There have been four deaths, a spokeswoman for the European Medicines Agency said on Thursday.

The European Union accounts for 14 of the cases of progressive multifocal leukoencephalopathy (PML), with two in Switzerland and eight in the United States.

Last Friday, the agency announced it had begun a review of the drug after reports of 23 cases of PML, sending shares in the drug's makers Biogen Idec Inc and Elan Corp Plc sharply lower.

Tysabri was temporarily withdrawn from the market in 2005 after being linked with the disease. It was reintroduced in July 2006 with stricter safety warnings.

Elan fell as much as 3 percent to a new year low on Thursday, before recovering, while Biogen was down 0.7 percent by 1615 GMT. (Reporting by Ben Hirschler; Editing by David Cowell)

Source: Reuters © Thomson Reuters 2009 All rights reserved (29/10/09)

Biogen Idec’s key multiple sclerosis drug Tysabri had been linked to 23 worldwide cases of a potentially deadly brain infection called progressive multifocal leukoencephalopathy, or PML — with most confirmed cases centered in Europe, in particular Germany. Could there be a link between the seemingly higher prevalence of Tysabri-related PML cases in Germany and lack of oversight?

Hard and fast data confirms that from July 2006 (when Tysabri marketing resumed) to September 8, 2009, thirteen worldwide cases of Tysabri-related PML occurred in patients being treated for MS with Tysabri monotherapy. Of these, only four cases were patients in the United States, according to an FDA Post-marketing Drug Safety report.

Germany is an important MS market for Biogen. Aside from the U.S., Europe is home to four of the top seven markets — Germany, Italy, UK, and Spain — in terms of commercial dollars spent on disease modifying drugs for use in MS, according to an analysis of the global MS market by the pharmaceutical research outfit Visiongain.

Patients receiving monthly Tysabri infusions in the U.S. must be enrolled in the TOUCH Distribution Program overseen by Biogen, which involves (i) extensive monitoring of all patients for signs of PML and (ii) education of all patients and providers, with strong emphasis communicated to all parties that the drug is contraindicated for use in MS patients taking any drugs that may increase their risk of opportunistic infections, including drugs that lower immune function (e.g., azathioprine, chemotherapy, cyclosporine) or immunomodulators, such as the interferon-based disease-modifying therapies.

Aside from voluntarily enrollment of patients in Biogen’s Phase 4 trial, TYGRIS (Tysabri Global Observation Program in Safety), which is a prospective 5-year, 5000-patient cohort observational study to further evaluate PML risk and overall safety of Tysabri therapy, there are few — if any — restricted distribution programs in place throughout Europe.

As mentioned, most of the other reported cases of PML are alleged to have occurred in Germany, where oversight is purportedly lax, especially in the monitoring of the presence of latent JC virus  and a mandated prior “washout” phase required in patients recently removed from other immunosuppressant therapies, both high-risk factors for development of PML. However, since late summer, German authorities have been working with the company to make sure “appropriate use of Tysabri is monitored and followed up with [patients],” Chief Executive Jim Mullen said on the third-quarter earnings call.

The duration of therapy in the newly diagnosed PML patients is unknown. That said, lax supervision in German — and other European — MS treatment facilities could be a contributing risk factor behind the higher incidence(s) and prevalence of reported PML cases.

In the last 12 months, Biogen has engineered relationships between academic reference centers and many of the larger MS clinics in Germany so that the prescribing of Tysabri can occur in a more structured environment — in compliance with a common protocol developed and published by the Medical Advisory Board of German MS, according to chief operating officer Robert Hamm. To date, 250 top German MS treatment centers are linked to 40 reference centers, he said on the call. This initiative should play out in the company’s favor as European regulators re-assess the risk-benefit profile of Tysabri.

Source: BNET © 2009 CBS Interactive Inc. (29/10/09)

The European Medicines Agency Committee for Medicinal Products for Human Use has started a review of the benefits and risks of Tysabri, in view of reports of 23 cases of progressive multifocal leukoencephalopathy (PML) worldwide since Tysabri has been on the market.

This review is initiated to discuss any additional measures necessary to ensure the safe use of Tysabri and how to balance the risks to the patients against the benefits of the treatment.

Tysabri is indicated for patients suffering from highly active relapsing remitting multiple sclerosis with high disease activity despite treatment with a beta interferon and for patients with rapidly evolving severe relapsing remitting multiple sclerosis.

A case report of brain cancer (primary central nervous system lymphoma) developing in a person being treated with Tysabri® (natalizumab, Biogen Idec and Elan Pharmaceuticals) has been published. Achim Berthele, MD (Technische Universitate Munchen, Germany) and colleagues report the case in Annals of Neurology (2009:66[3];403 - 406).

Based on this single report, it cannot be confirmed that Tysabri caused (or predisposed to) the lymphoma. However, the authors suggest that any development of new or unusual neurological signs or symptoms in a person taking Tysabri should prompt a diagnostic workup for possible complications. Such monitoring is required in people enrolled in the TOUCH risk management program in the U.S.

Background: Tysabri is a laboratory-produced monoclonal antibody that is approved for patients with relapsing forms of MS to delay the accumulation of physical disability and reduce the frequency of clinical exacerbations. It is designed to hamper movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier” into the brain and spinal cord.

In the general population, primary central nervous system lymphoma, or PCNSL, is most often diagnosed in the elderly and in individuals whose immune systems have been suppressed by medications or disease. There is no reported increase of PCNSL in individuals who have multiple sclerosis.

Details: A 40-year old man from Germany with relapsing-remitting MS had been treated previously with beta interferon and azathioprine. A previous brain biopsy had shown no signs of lymphoma. He developed partial loss of sensation (hypoanesthesia) on his right side after having received 21 doses of Tysabri. MRI-detected lesions were not typical of multiple sclerosis, prompting tests that led to the diagnosis of primary central nervous system lymphoma.

The authors tested the lymphoma, a high-grade B-cell non-Hodgkin lymphoma, for the presence of Epstein-Barr virus, since this virus has been associated with PCNSL when it develops in immune-suppressed individuals. They found no evidence of the virus in the lymphoma tissues, somewhat reducing the likelihood that the tumor was related to Tysabri-induced immunosuppression.

Comment: “This report underscores the importance of carefully tracking patients on powerful medications like Tysabri and remaining vigilant for new neurologic signs in people on this medication,” said Dr. John R. Richert, executive vice president of research and clinical programs at the National MS Society.

It cannot be confirmed from this single report that there is a causal link between Tysabri administration and the occurrence of primary central nervous system lymphoma. However, careful monitoring for new or unusual neurological signs and symptoms in those taking Tysabri, which is required in those enrolled in the TOUCH risk management program in the U.S., should be adequate for detecting possible signs of brain lymphoma.

Source: National MS Society (US) (21/10/09)

The Food and Drug Administration has updated the safety information related to multiple sclerosis treatment Tysabri, sold by Biogen Idec Inc. and Elan PLC, to include information about incidences of a rare brain infection.

The drug's label hasn't changed, and the agency stressed that the overall rate of patients developing progressive multifocal leukoencephalopathy, or PML, remains below the one-in-1,000 rate implied on the label.

Tysabri, widely considered to be a highly effective treatment for the debilitating disease, was pulled from the U.S. market in 2005 for 18 months because of PML concerns, and 13 cases of the infection have been confirmed since its relaunch.

"Tysabri is a compelling option for the treatment of MS, and PML remains a rare adverse event," a Biogen spokeswoman said.

In its update, the agency warned that the risk of developing PML "appears to increase with the number of Tysabri infusions received" and that the average number of infusions received before the diagnosis of PML was 25.

"There is minimal experience in patients who have received more than 35 infusions of Tysabri," the update said. Tysabri is delivered through an intravenous infusion about once a month.

Duration of therapy is widely believed to play a role in Tysabri's PML risk. Biogen has said there is no clear connection to duration and has opposed patients taking treatment breaks - referred to as "drug holidays" - because it can cause MS symptoms to return.

"It wouldn't be prudent to draw any conclusion at this time, based on the small number of patients that have developed PML," the Biogen spokeswoman said regarding the duration issue.

As of June 30, about 43,300 patients were taking Tysabri, with more than 30,000 on it for more than a year, and about 10,000 on it for more than two years.

Although the rate of PML infection remains below 1-per-1,000 patients, the FDA said the current rate of PML in patients who have received at least 24 infusions ranges from 0.4 to 1.3 per 1,000 patients.

"At this time, the FDA is not requiring changes regarding PML to the Tysabri prescribing information or to the Tysabri risk management plan, called the TOUCH Prescribing Program," the update stated.

Tysabri is key to the future growth of both Biogen and Elan, and Wall Street has focused on the PML cases. The drug receives strong support from patients and doctors because of its perceived effectiveness. That support has remained steady because patients are well aware of the PML risk before they start taking Tysabri for the otherwise debilitating disease of MS.

Tysabri is one of several immune system-suppressing therapies that have been linked to PML, including Rituxan, sold by Biogen with Roche Holding AG unit Genentech, and Raptiva, a psoriasis drug that Genentech pulled from the market earlier this year because of the issue.

Source: The Wall Street Journal  ©2009 Dow Jones & Company, Inc.(18/09/09)

Biogen Idec Inc said on Tuesday it would be premature to conclude that the risk of developing a potentially deadly brain infection increases the longer patients take its multiple sclerosis drug Tysabri.

The company told investors at the Morgan Stanley healthcare conference that despite two new reports of patients who have developed progressive multifocal leukoencephalopathy, or PML, it is too early to draw any specific conclusion.

Cambridge, Massachusetts-based Biogen, which sells Tysabri with Irish drugmaker Elan Corp Plc ceased updating investors with the number of patients who developed PML at the end of July, as part of a broader strategy to focus more on the positive aspects of the drug.

At that time, Biogen had confirmed 11 cases of PML since the drug was relaunched in July 2006. It had been temporarily withdrawn in 2005 because of its links to PML.

Recently, however, two new cases have emerged, bringing the total to 13. One case was reported in the New England Journal of Medicine. The other was reported by Ralf Gold, of the Ruhr University Bochum in Germany, who presented the data recently at the European Committee for Treatment and Research in Multiple Sclerosis.

Both cases occurred in Europe.

As of June 30, about 43,300 patients were taking Tysabri. More than 30,000 had taken it for more than a year and about 10,000 for more than two years. Most cases of PML so far have developed in patients taking the drug for more than a year.

Biogen has said it is looking into all possible risk factors associated with PML, including duration of treatment, but that it would be premature to conclude that there is a definitive correlation between duration and risk.

The company said it would notify investors if the number of patients who develop PML exceed the rate of one in 1,000 patients, which is the rate listed in the drug's prescribing information.

Source: Reuters © Thomson Reuters 2009 (16/09/09)

Two more cases of a rare brain infection have emerged in users of the multiple-sclerosis drug Tysabri, sold by Biogen Idec Inc. and Elan PLC, the first such incidences since Biogen stopped updating investors of the situation in July.

At that time, Biogen had confirmed 11 cases of progressive multifocal leukoencephalopathy, or PML, since the drug's relaunch in July 2006; Tysabri was pulled from the U.S. market in 2005 because of PML concerns.

A Biogen spokeswoman said the Cambridge, Mass., biotech company is neither commenting on nor confirming the existence of additional cases as long as the PML rate is consistent with the rate of one-in-1,000 patients implied by the label. The new cases appear to be in line with the label's rate.

An editorial published in the New England Journal of Medicine last week revealed a new case that occurred in Europe.

The latest case, also in Europe, was confirmed by Ralf Gold of the Ruhr University Bochum in Germany, who presented the case at the European Committee for Treatment and Research in Multiple Sclerosis that ended Saturday.

Like any public company, Biogen is required to disclose developments deemed material to its business, but the biotech company has said Tysabri's risk profile is accurately detailed in its label after providing weekly updates on new PML cases through July 24, the third anniversary of Tysabri`s relaunch.

Duration of therapy is believed to play a role in Tysabri's PML risk as most cases occurred after patients took the drug for more than a year. Biogen has opposed patients taking treatment breaks--referred to as "drug holidays"--because it can cause MS symptoms to return.

As of June 30, about 43,300 patients were taking Tysabri, with more than 30,000 on it for more than a year, and about 10,000 on it for more than two years.

Tysabri receives strong support from patients and doctors because of the drug`s perceived effectiveness. That support has remained steady because patients are well aware of the PML risk before they start taking Tysabri for the otherwise debilitating disease of MS.

Wall Street has closely watched the number of cases in gauging Tysabri's sales trajectory because it is the key growth driver for both companies.

Sanford Bernstein analyst Geoffrey Porges said the two new cases "[add] to the dissatisfaction about the company's decision to suspend regular disclosure of the rate of cases, particularly as a large bolus of patients are now reaching what appears to be a point of increased event risk."

Mr. Porges said the new cases were "not necessarily alarming" because the ratio remains below the label-implied rate, but he stressed that there seems to be a connection to PML risk and duration of therapy.

PML re-emerged in Tysabri patients in July 2008, two years after the relaunch, and Biogen began issuing weekly updates in January after receiving criticism for its previous policy of disclosing new cases through 8-K filings with the Securities and Exchange Commission.

Source: The Wall Street Journal Copyright ©2009 Dow Jones & Company, Inc.(15/09/09)

Different methods of weighing the risks and benefits of medical treatments lead to varying conclusions about their safety

Ever since the powerful multiple sclerosis drug Tysabri returned to the market in July 2006, a key issue for patients has been the risk of contracting progressive multifocal leukoencephalopathy, or PML, a dangerous brain infection associated with the drug.

PML's appearance in three of the 3,000 patients who took Tysabri during clinical trials was the reason the drug was pulled from the market in 2005 -- and its return was made possible only under patient-monitoring rules imposed on Tysabri maker Biogen Idec Inc. by the Food and Drug Administration.

Despite these rules, it has been hard for many MS patients to get a clear picture of the odds of getting PML during long-term Tysabri use since the drug is relatively new. In the three years since the drug's return, Biogen reported 11 new PML cases among 56,500 patients who have tried the drug.

Tysabri underscores a central mathematical issue in assessing risks and benefits of medical treatment -- one that has also shown up in calculating the risk of blood clots among heart-stent users, and in figuring out how beneficial chemotherapy is in treating lung cancer.

Simply put, the issue is a matter of whether to adjust for time. In other words, should the chances of contracting a harmful side effect be calculated by figuring out the simple percentage of all those taking the drug who have come down with the side effect? Or should those calculations be adjusted for the duration that patients have been treated?

The former method calculates what's called an "absolute" percentage. The latter, used widely in medical studies and by insurance actuaries, takes into account that risk changes over time: For example, someone who drives a car only one day during his lifetime is less likely to be in a crash than someone who drives for 20 years.

Using the absolute method, Biogen in late April said cases of PML that had occurred since the drug's return were 1.2 per 10,000 -- or about one in 8,700 -- extrapolated from the six then-known cases among 52,000 Tysabri takers.

Biogen says now that the rate of PML among Tysabri users "remains very low and well below the rate suggested by the U.S. product label," which discloses the three cases among 3,000 patients in clinical trials, and was revised in late 2008 to say there have been more cases since reintroduction. A spokeswoman said Tuesday that the company won't be disclosing new cases of PML and won't recalculate the risk unless it changes significantly.

But taking into account the five additional cases the company has reported since April, and using the actuarial method, the risk comes out to about one in 1,200 -- much closer to the one-in-1,000 threshold that some analysts have said might cause doctors to become more cautious about prescribing the drug. Biogen says the absolute method is more appropriate to measure rare risks.

Some doctors have begun using actuarial calculations to estimate Tysabri's risks. For a chronic disease like MS, where treatment can last eight or 10 years, the long-term risk is probably different than for somebody who has only a short course of the drug.

Robert Fox, a neurologist and director of the MS center at the Cleveland Clinic, calculates that for patients on Tysabri for more than 30 months, the risk is higher than one in 1,000, while for those on it for 18 months it is only 0.21 per 1,000. He says the clinic has been suggesting to patients on the drug for two or three years should "rotate off" the drug and onto a different therapy.

Mark Schoenebaum, an analyst at Deutsche Bank who follows Biogen, has said that a one-in-1,000 incidence rate would amount to a level that would cause patients to be more reluctant to take the drug, and doctors to be more reluctant to prescribe it.

The Wall Street Journal's analysis, based on standard actuarial methods commonly used in medical research, was reviewed by David Harrington, a biostatistics professor at Harvard University's School of Public Health who specializes in calculating medical risks. He said the calculations were accurate and an appropriate way to calculate the risk.

Biogen reviewed a copy of the calculations and disagrees with them. "The WSJ methodology is flawed because it uses the wrong type of model...in the wrong manner," the company said in a statement.

The two mathematical methods in calculating risks have led to prior disputes. In 2006, Boston Scientific Corp. and Johnson & Johnson disagreed over whether their models of drug-coated heart stents -- tiny scaffolds that prop open clogged arteries -- caused blood clots years after implantation.

J&J found no increase in the percentage of patients with clots in its coated stent. Boston Scientific used the actuarial method to measure its coated stent and did find an increase, by about one clot per 200 people per year. That led to unwelcome headlines for Boston Scientific. But a later study, in the New England Journal of Medicine, analyzed both stents with the same technique. Both products showed the same increase in clots. Representatives for Boston Scientific and J&J declined to comment.

Similarly in 2005, a Canadian clinical trial inaugurated the use of chemotherapy to treat lung cancer after demonstrating that the treatment reduced mortality by 31%. Half the people in the study were given chemo, and half weren't.

But the results didn't mean that chemo decreased actual lung-cancer deaths -- only that it would extend the life of patients. In fact, after eight years, the study estimated that the same fraction of people would die with treatment as without -- about half. Since people on chemo lived longer, by about 21 months, the study could truthfully report that treatment reduced the average death rate during the study.

Trying to estimate Tysabri's risks runs into the same issue of accounting for risks over time. The drug, also sold by Elan Corp. of Ireland, is widely considered the most potent MS treatment on the market.

Although the company declines to quantify the risk based on current data, using the absolute method it applied in April, the rate would come out to one in 5,140 -- or 11 of the 56,500 patients who have taken the drug since its return.

That lumps together everybody who has tried Tysabri, no matter how long. Biogen says about 200 new patients keep starting every week. Since the drug was relaunched only in 2006, fewer than half of the patients taking it have been using it for more than 18 months. It takes time for the infection to develop and to be recognized. Mathematically, averaging all the patients together, irrespective of how long they have been observed taking Tysabri, underestimates the risk to a long-term patient.

But using the actuarial method, which takes into account that different patients have been observed on the drug for different amounts of time, the rate comes out to one in 1,200 for three years of use.

The actuarial method estimates the chance of making it through various time periods without getting PML. For example, according to Biogen, nobody got PML in the first year of treatment, so the chance is 100% -- risk free. About 30,600 people received at least a year of Tysabri, and four of them were infected before they reached 18 months. So the chance of successfully making it through that period is about 99.99%. About 10,000 people have been observed on Tysabri for between two and three years, and seven got PML -- a 99.93% chance of not getting PML during the third year.

Multiplying the figures together -- 100% times 99.99% times 99.93% -- results in a 99.92% chance of not getting PML during the first three years of treatment. In other words, there's an 0.08% chance of getting the infection. That works out to one in 1,200.

Source: The Wall Street Journal ©2009 Dow Jones & Company, Inc (10/09/09)

Relations appear to be increasingly strained between Biogen Idec and the Irish drug company Elan, its partner for the distribution and development of the multiple sclerosis drug natalizumab (Tysabri). Elan said today that it has filed suit against Biogen over the Cambridge, MA-based biotech firm’s objections to Elan’s deal announced last month with affiliates of health products giant Johnson & Johnson.

Elan’s deal with Johnson & Johnson gives Elan the option to get financing from J&J to acquire Biogen’s rights to natalizumab if Biogen is acquired or undergoes some other change of control, according to Elan. And, according to Reuters, Elan’s $1.5 billion deal with J&J also gives J&J the option to purchase Biogen’s 50 percent stake in the Tysabri business if there’s a change in control at Biogen. Biogen has told Elan that Elan’s deal with J&J breaches the partnership agreement for the drug between Elan and Biogen. Elan disagrees. A Biogen spokeswoman wrote in an e-mail that the company has no comment about Elan’s recent legal action. The lawsuit Elan filed in federal court in New York seeks “declaratory and injunctive relief” that essentially confirms that Elan’s deal with J&J complies with its collaboration agreement with Biogen.

Biogen has been the subject of buyout rumours in recent years, and in late 2007 ended an official search for a buyer after the activist investor and Biogen shareholder Carl Icahn pushed for a sale of the company: Biogen said that December that it didn’t receive any qualified acquisition bids during the sales process. Biogen’s collaboration with Elan has factored into such buyout discussions, at least in part because of the importance of natalizumab to Biogen’s business. The drug, which generated $588.6 million in 2008 revenue for Biogen, is one of the company’s top three products, along with MS drug interferon beta-1a (Avonex) and rituximab (Rituxan) for rheumatoid arthritis and non-Hodgkin’s lymphoma. Biogen and Elan, which discovered natalizumab, entered their development and marketing agreement in 2000.

Elan issued a statement that said: “This is the same agreement we have been operating under for the last nine years. It is unfortunate that, because of Biogen Idec’s actions, Elan was left with no alternative but to seek court intervention to protect its interest.”

Biogen markets natalizumab for multiple sclerosis in the U.S. and Europe, and Elan has responsibility for selling the drug in the U.S. for the intestinal disorder Crohn’s disease. Biogen has said in previous financial reports that it has pinned much of its near-term revenue growth on increased sales of natalizumab.

Source: Xconomy © 2007-2009, Xconomy, Inc (07/08/09)

An 11th patient taking Biogen Idec Inc's multiple sclerosis drug Tysabri has developed a potentially deadly brain infection since July 2006, when it was reintroduced to the market.

In the latest confirmed case of progressive multifocal leukoencephalopathy, or PML, the patient took Tysabri for 29 doses, continuing the trend of the last six reported cases of the infection, where each patient had therapy for two years or longer.

The latest patient was located in the USA, the third American to have developed the infection. Of the 11 reported cases, one patient has died.

The PML incidence rate remains below the long-projected risk rate of one in 1,000 patients for those patients receiving the therapy for 12 months or 18 months.

The Cambridge, Massachusetts-based biotech company released the news on its website late on Friday. Tysabri, which Biogen sells in conjunction with Irish drugmaker Elan Corp Plc, is considered critical to the future growth of both companies.

The drug was temporarily withdrawn from the market in 2005 after it was linked with a brain infection known as progressive multifocal leukoencephalopathy, or PML. It was brought back in 2006 with stricter safety warnings. Biogen has recently adopted a more aggressively upbeat tone in marketing the drug, insisting physicians are becoming more comfortable with risk of PML.

That approach appears to be working. Sales of Tysabri accelerated in the second quarter, rising to $254 million from $200 million a year ago. The company said the drug is on track to generate some $1 billion in sales this year. Even so, some analysts believe doctors may take patients off the drug for certain periods of time. At the end of June, about 43,300 patients were on Tysabri, compared with 40,000 at the end of March.

Biogen and Elan originally predicted 100,000 patients would be taking the drug by the end of 2010. The companies still believe they will reach that figure, but not within that time frame.

This is the last case of PML that the company plans to announce on its website. Biogen said on its earnings conference call earlier this month that it would in future communicate new cases by word of mouth to physicians and patient advocacy groups.

Source: Reuters © Thomson Reuters 2009 (27/07/09) & Updated 30/07/09 Source: Medical News  Today © 2009 MediLexicon International Ltd

Biogen Idec has reported that a tenth multiple sclerosis patient being treated with Tysabri was diagnosed with a serious brain infection.

The latest case of progressive multifocal leukoencephalopathy (PML) occurred outside the U.S. in a patient on Tysabri therapy for 30 months. Four Tysabri patients on therapy for more than 30 months have now contracted PML, including the last three reported cases.

This is raising concerns that the risk of a multiple sclerosis patient contracting PML increases with longer duration of Tysabri therapy. The overall incident rate of PML is still very small and Biogen Idec has presented scientific data disputing the notion that PML risk increases with longer Tysabri use.

However, some doctors are beginning to cycle patients off Tysabri after two years or putting patients on drug holidays. If this trend continues, Tysabri patient and revenue growth -- already stunted -- could stall further.

Source: The Street.com © 1996-2009 TheStreet.com, Inc.(29/06/09)

Biogen Idec Inc. reported that a ninth patient on its multiple sclerosis drug Tysabri, sold with Elan PLC, has developed a rare brain infection, the third such report since mid-May.

A suspected link to progressive multifocal leukoencephalopathy, or PML, led to Tysabri being pulled from the market for 18 months beginning in 2005. Previously the company had reported that eight people had confirmed cases of PML, with one dying, since the relaunch. The most recent case was reported one week ago.

The drug was allowed back on the market in 2006 because of its effectiveness in fighting the degenerative disease and the incidence of PML remains well below the long-projected risk of one in 1,000 patients developing the infection.

"PML is still very rare in Tysabri-treated patients," said Biogen spokeswoman Shannon Altimari.

The patient with the latest confirmed PML case took 34 doses of the monthly medication and was located overseas. Only two of the nine cases since last July were located in the U.S.

Altimari said Biogen doesn't know why confirmed cases of the condition are more common overseas, but that the company is constantly performing research to better understand the infection.

Much is unknown about PML, but it is thought to be caused when the JC virus, which most people carry, attacks the central nervous system in those with weakened immune systems, often leading to an irreversible decline in neurologic function and death.

It is thought that Tysabri patients with PML have had a better prognosis because of earlier detection and treatment with plasmapharesis, a process that removes large molecules from the blood, speeding up Tysabri's removal and allowing the immune system to fight the infection.

Tysabri is one of several immune-system-suppressing therapies that have been linked to PML, including Rituxan, sold by Biogen with Roche Holding AG (RHHBY) unit Genentech, and Raptiva, a psoriasis drug that Genentech pulled from the market earlier this year because of the issue.

Earlier this year, Biogen retreated from its long-held goal to reach 100,000 patients on Tysabri by the end of 2010. As of the end of March, about 40,000 patients were using Tysabri, up from 37,600 patients at the end of December.

Some believe that the duration of therapy plays a role in Tysabri's risk. About 6,800 patients have used the drug for more than two years, as of the end of March.

Biogen is posting a case update on the Internet every Friday at 4:30 p.m. EDT until July 24 - the third anniversary of the drug's relaunch - by which time it expects the risk/benefit profile of Tysabri to be clearer.

Tysabri had 2008 sales of $813 million, but the longer-term sales trajectory, which is key to Biogen's future growth, will depend on the true incidence of PML, which is still coming into focus.

Source: NASDAQ © The NASDAQ Stock Market, Inc. (22/06/09)

Biogen Idec Inc. said a patient taking its multiple sclerosis drug Tysabri was diagnosed with a life-threatening brain illness, the eighth case reported in the last year.

The patient was confirmed to have progressive multifocal leukoencephalopathy, or PML, on June 10, according to a report on Cambridge, Massachusetts-based Biogen’s Web site. About 56,700 patients have been treated with Tysabri, the company said.

Biogen and marketing partner Elan Corp. pulled Tysabri from the market in 2005 after three patients developed the brain infection, including two who died. The U.S. Food and Drug Administration allowed sales to resume in July 2006 after deciding benefits for slowing MS relapses outweighed the risk. There were no reported infections for about two years after the drug’s reintroduction.

The likelihood of getting PML from Tysabri is about 1 in 1,000, according to the drug’s label. The infection occurs when a common germ, called JC virus, mutates, then evades the body’s immune defenses and penetrates the brain, causing irreversible damage. Researchers theorize that Tysabri may subdue defenses meant to keep the virus out of the brain. The virus breeds in brain cells, destroying them when it replicates.

On April 9, Genentech Inc., which was acquired in March by Roche Holding AG, announced it was pulling its psoriasis treatment Raptiva from the U.S. market because of the drug’s link to PML. Three patients were diagnosed since October and two died. Other drugs linked to PML include Roche’s Cellcept, used to prevent transplant rejections; Biogen and Roche’s cancer drug Rituxan; and Genzyme Corp.’s leukemia drug Campath.

Soure: Bloomberg.com Copywrite 2009 Bloomberg L.P (14/06/09)

Biogen Idec’s Tysabri will play a significant role in the second line setting for the treatment of relapsing-remitting multiple sclerosis (MS), despite looming competition from new oral agents in development, neurologists told Pharmawire.

The current standard of care in this setting includes Teva’s Copaxone and the interferon drugs Avonex, Betaseron, and Rebif. Tysabri is also used in more advanced patients, who have failed on alternative therapies. Novantrone is a chemotherapy drug, which is also FDA approved to treat worsening relapsing MS or secondary progressive MS.

Although patients may prefer these new oral pills over the current injectables, the leading orals in development - Novartis’ FTY720 and Merck-Serono’s cladribine - will likely face a risk management procedure (REMS) if approved, and may see slower than expected adoption in the real-world setting, specialists noted.

Both cladribine and FTY720 were associated with significant toxicities over the current standard of care, and would likely only see approval with a risk management procedure, similar to what is currently being utilized with a currently marketed drug, Elan’s Tysabri, neurologists noted.

Some of these new oral agents will fail to gain approval and for those that do make it, there will be rigorous pharmacovigilence programs requested by the both the FDA and EMEA, according to Dr Hans Peter Hartung, professor and chairman of the department of neurology at University Hospital Dusseldorf, Germany. These agents will see slow uptake by the majority of neurologists because they will want to see how safety evolves in post-marketing studies, he explained. ”Enthusiasm for these agents has been dampened,” Hartung said.

Tysabri, developed by Biogen and Elan, was withdrawn from the market in 2005, after patient reports of a rare, and potentially lethal brain inflammation known as PML, or progressive multifocal leukoencephalopathy. The drug was reintroduced to the market in 2006 under a REMS, the TOUCH program, in which patients are continuously monitored for PML. Recently, a sixth patient was diagnosed with PML.

In Novartis’ Phase III TRANSFORMS study, the lower 0.5 mg dose with FTY720 demonstrated a 52% lower relapse rate at one year for patients, compared to Biogen’s Avonex. The higher 1.25 mg dose showed a 38 percent greater reduction in risk for the same endpoint for the 1.25-mg dose. Other oral drugs in development include Biogen’s BG-12, Teva’s laquinomod and Sanofi’s teriflunomide.

Merck-Serono’s pivotal Phase III CLARITY trial, reported a 58% relative reduction in annualized relapse rates with respect to placebo on the low-dose regimen.

Overall, there were 47 patients in the CLARITY study that accessed rescue medication with Rebif, according to a spokesperson for Merck-Serono. Nine patients in the higher 5.25 mg/kg treatment group, 11 patients in the 3.5 mg/kg cladribine tablets treatment group, and 27 patients in the placebo treatment groups received rescue medication.

There have also been concerns with cladribine’s unknown effects on long-term immunosuppression, which may be irreversible, some neurologists speculated. Lymphopenia and leukopenia occurred more frequently in patients on cladribine - six patients in total died, two from each of the cladribine groups.

Dr Daniel Kantor, an investigator on Novartis’ FTY720 and Genzyme’s Campath trials, said there were four malignancies, from patients on cladribine, which were all in different organ systems. Although there is no evidence to suggest the risk of brain tumours yet, the appearance of one case would hurt this drug in clinical trials. Kantor is also medical director of the Neurologique Foundation in Florida.

Dr Douglas Jeffrey, an investigator on Teva’s laquinimod trials and associate professor in Wake Forest University’s department of neurology and MS specialty care, speculated that due to cladribine’s effects on long-term immunosupression, patients who fail treatment cannot go on rescue therapy such as Tysabri, because they will be at an increased risk of developing PML. Cladribine also has safety risks on long-term immune function, and is a dangerous drug, he added. Patients taking Novartis’ FTY720 also saw a number of cases of skin cancer, he added.

Tysabri’s place in the new market to some extent depends on the incidence of PML, Hartung said. If the incidence stays similar to what it was when it was approved, it will continue to play an important role in treatment, he said. Tysabri has played a significant role in the second line setting in relapse-remitting MS (RRMS) and in patients who don’t respond to interferon and Teva’s Copaxone, added Dr AM Rostami, chair of the department of neurology at Thomas Jefferson University.

While Tysabri has been effective in decreasing relapses and MRI lesions, PML is a concern, Rostami agreed. Out of 38,000 patients, there have only been a few cases and the hope is that there will not be more. If incidence remains low, Tysabri has a chance in the market alongside the new agents, he agreed.

PML has been carefully monitored via the company’s TOUCH program. ”I suspect that more potent drugs may also be associated with risks that mandate a cautious approach,” Hartung said. Neurologists will follow the new agents to see how things develop since side effects are not always revealed in Phase III studies, he said. If the risk-benefit ratio stays the same for Tysabri, it will maintain or increase its position in the market in the next four to five years, he said.

Dr John Richert, executive vice president of research and clinical programs at the National Multiple Sclerosis Society, said where Tysabri sits in the market two to three years from now will largely depend on the incidence of PML, and whether it stays within the 1:1000 ratio as stated on the label. The issue will be whether that risk stays at the estimated 1:1000, increases or decreases, he added. There are 40,000 to 45,000 patients on Tysabri, he added.

”I think in the short term, it’s hard to predict if anything will be pushed out,” said Timothy Coetzee, Ph.D., executive director of Fast Forward, a venture philanthropy unit of the National Multiple Sclerosis Society, in response to whether new oral MS drugs would end up replacing Tysabri in the future. Coetzee said the medical community’s understanding of the disease is improving significantly, and it is hard to predict what the safety profiles of these new oral agents will be.

But according to Dr Emmanuel Bartholome, a neurologist at the Tivoli Hospital in Brussels, PML will be also eventually be associated with these newer agents. These agents are more potent, he explained, and it is not possible to induce further immunosuppression. ”We have hit the roof,” he added. Ultimately, all MS patients will have to go to MS centers for treatment and neurologists will have to see patients more frequently to monitor for these effects, he said.

In terms of relapse rate, cladribine, FTY720 and Tysabri have all reported a similar figure between 50-70%, Bartholome said. There will be some competition in the second line setting, he added.

”I think in five years, we’ll know the real risk of PML with Tysabri,” said Dr Jack Burks, clinical professor of neurology at the University of Nevada.

Source: FT.com © Copyright The Financial Times Ltd 2009. (13/05/09)

The risk of developing progressive multifocal leukoencephalopathy (PML), a viral brain infection, in patients with multiple sclerosis (MS) taking the drug natalizumab (Tysabri) appears to be much lower — and the infection less deadly — than previously estimates, according to new postmarketing surveillance data.

Previous research found that the risk of developing PML was 1 in 1000, but new data show that the risk is closer to 1.2 per 10,000 patients, according to Carmen Bozic, MD, vice president and global head of drug safety and risk management for the maker of natalizumab, Biogen Idec, in Cambridge, Massachusetts.

Dr. Bozic delivered an updated overview of the risks and benefits of natalizumab during the American Academy of Neurology (AAN) 61st Annual Meeting.

Approved In 40 Countries

Natalizumab is approved in over 40 countries for the treatment of relapsing forms of MS to reduce the frequency of relapses and delay worsening of physical disability in patients who have had an inadequate response to or are unable to tolerate another MS medication. The drug is approved in the United States, Canada, Europe, Australia, and parts of the Middle East and Latin America. It is also approved in the United States to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease.

Natalizumab is an antibody rather than an interferon; Biogen Idec also manufactures an interferon beta1-a drug (Avonex) for newly diagnosed MS patients. It works by preventing white blood cells from entering the brain and attacking nerves.

The data presented were taken from the Tysabri Outreach: Unified Commitment to Health (TOUCH) prescribing program and the Tysabri Global Observation Program in Safety (TYGRIS), both part of a global risk-management program to further evaluate the safety of natalizumab. TOUCH is a mandatory prescribing program for all patients, physicians, and infusion centers in the United States that ensures "appropriate and informed use of natalizumab," the researchers note. TYGRIS is a global voluntary observational study evaluating the long-term safety of natalizumab in clinical practice. Data from countries that do not participate in either TOUCH or TYGRIS were also collected.

As of the end of March 2009, or about 3 years after approval in the United States and the European Union, approximately 52,000 patients had been treated with natalizumab in the postmarketing setting. "This is more than 10 times the exposure we had in clinical trials," said Dr. Bozic.

Long-Term Exposure

As well, there is now much more information on the drug's long-term exposure in the postmarketing setting, she said. To date, about 24,900 patients have been taking the drug for 12 months or longer, 14,400 for 18 months or longer, and 6800 for 24 months or longer. Some patients have taken the drug for more than 2.5 years, she added.

"So both overall exposure and long-term exposure is significantly greater than we had in the original clinical trials, and that gives us a very robust ability to evaluate the safety of the drug," she told Medscape Neurology & Neurosurgery.

Of the 52,000 patients who have taken the drug, there have been 6 cases of PML, or an incidence of approximately 1.2 per 10,000 patients treated. "It's trending lower than what we saw in the clinical-trial setting," said Dr. Bozic.

The 6 patients — 3 men and 3 women aged 37 to 59 years — had taken the drug as monotherapy for periods ranging from 12 to 31 months. "This is a highly variable duration of treatment," noted Dr. Bozic.

No Patterns With PML

Nothing seems to set these 6 patients apart from other MS patients, she noted. There was no pattern, for example, in terms of age — they were all about the same age as the MS population taking natalizumab — or their past health history. "We're actively engaged in research on PML to see if we can better understand specific risk factors for the disease; for example, whether there are specific host factors or specific viral factors," said Dr. Bozic. "But we don’t have the answers on that yet; we're diligently working on it."

Of the 6 patients, 5 are still alive. "That's good news," said Dr. Bozic. "The outcome of the patients in the postmarketing setting is looking better than what we saw in clinical trials from a survival perspective." While rare, PML is considered to be a highly fatal disease.

Researchers also investigated whether the risk for PML increased with length of treatment, but "we haven’t seen a clear-cut pattern to date," said Dr. Bozic.

The incidence of PML in patients taking natalizumab for 1 year or more is 2.4 per 10,000 patients, 1.4 per 10,000 in patients treated for 18 months or more, and 3 per 10,000 in patients treated for 2 years or more, with confidence intervals "that are overlapping," said Dr. Bozic.

Outcomes "Trending Better"

"The incidence of PML doesn't seem to vary significantly with treatment duration," she said. "It's still a very small data set — only 6 patients — but based on these 6 patients, we think the outcomes appear to be trending better than what we saw in the clinical-trial setting."

As soon as PML was detected in the 6 patients, doctors stopped the drug immediately. To rapidly remove the drug from their system, the patients underwent either plasma exchange or immunoabsorption, "the idea being to allow the white blood cells to enter the brain and fight the infection," said Dr. Bozic. Four of the 6 patients also received the antimalaria drug mefloquine, which has been shown to have in vitro activity against JC viral replication; it is the JC virus that causes PML. "There are no clinical data, no proof, that it works clinically, but there are in vitro data, so on the basis of that, the doctors decided to give some of these patients that drug," she explained.

Three of the patients who developed PML had previously taken immunosuppressant therapy, which they had stopped between 3 months to 3 years before starting natalizumab.

The patient who died received immunosuppressant therapy prior to taking natalizumab and later, mefloquine, "but I don't think we can draw any conclusions about this, since it was only 1 patient," said Dr. Bozic.

Remain Clinically Vigilant

While this new information is encouraging, doctors who prescribe natalizumab to treat MS should still monitor their patients very closely for PML, stressed Dr. Bozic. "They need to be very clinically vigilant for any new or worsening neurological signs or symptoms that might be indicative of this disease, and if the patient does report any new neurological signs or symptoms, the doctor is instructed to stop the drug and evaluate the patient to see if they have PML."

In the United States, natalizumab is available only through a special restricted-distribution program. Treatment is administered every 4 weeks by infusion.

Natalizumab is regarded by many experts as the most effective MS drug on the market today. Patients on this drug showed a 68% reduction in relapse rate and a 54% reduction in the risk for disability progression compared with placebo, Dr. Bozic told meeting attendees. In a post hoc analysis, patients taking natalizumab were 69% more likely to experience a sustained improvement in physical disability compared with patients taking placebo, she said.

Comfort Level

Asked for her comment, Lily Jung, MD, an MS neurologist at the neurology clinic at the Swedish Neuroscience Institute, in Seattle, who was not involved in this research, said that she is "a big fan" of natalizumab and feels "pretty comfortable" with its risk/benefit ratio. However, she speaks with each of her patients separately about his or her comfort level with the therapy.

"It would make me feel a lot better if we had very specific guidelines about what to do based on evidence; for example, if x and y, then z for xx interval, yy indications, and zz test results," she said. "Unfortunately, we don't have that, so we have to look at how each individual patient fits within the framework of the therapies that are available, what we know about need for therapy in terms of overall disability reduction, exacerbation history, MRI findings, etc. Each neurologist needs to work with his or her patients to figure out whether for that patient the risk of PML is worth it."

Biogen Idec has the world's largest pipeline of MS drugs. At the AAN meeting, the company also presented data on some of its other MS drugs, including pegylated interferon beta-1a. Phase 1 data were presented, showing safety and tolerability of the new compound and supporting further development.

The pegylation process is expected to extend the half-life of interferon beta1-a, potentially prolonging the effect. Through once- or twice-monthly subcutaneous injections, the compound could offer MS patients a more convenient dosing schedule as well as fewer adverse effects, such as flulike symptoms, which are typical of the interferon class of therapies.

The study was funded by Biogen Idec. Dr. Bozic has received personal compensation for activities with Biogen Idec as an employee.

Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre said, "It is obviously good news to see that the incidence of PML looks much lower than was first supposed.  We would still like to see more investigation into the potential causal links between Tysabri and PML and of course the potential to develop this life-threatening condition does still remain"

Source: Medscape Medical News © 2009 Medscape, LLC and MSRC(06/05/09)

Biogen Idec Inc. said a patient taking its multiple sclerosis drug Tysabri was diagnosed with a life-threatening brain illness, the sixth case reported since July.

The patient, who has MS, was confirmed to have progressive multifocal leukoencephalopathy, or PML, on Wednesday and had been taking the drug for 31 months, according to a report on Cambridge-based Biogen Idec's website. The patient lives outside the United States, according to the report.

Biogen Idec and marketing partner Elan Corp. pulled Tysabri from the market in 2005 after three patients, two of whom died, developed the brain infection. The Food and Drug Administration allowed sales to resume in July 2006 after deciding benefits for slowing MS relapses outweighed the risk. There were no reported infections for about two years after the drug's reintroduction.

More details on this case and others will be provided at medical meetings, said Shannon Altimari, a spokeswoman for Biogen Idec.

As of the end of March, about 40,000 patients worldwide were on Tysabri, and about 56,700 patients have used the drug, according to Biogen Idec. The likelihood of getting PML from Tysabri is about 1 in 1,000, according to the drug's label

Source: Boston.com © 2009 Globe Newspaper Company.(19/04/09)

The Food and Drug Administration warned 14 major pharmaceutical companies about brief Internet ads that accompany searches on Google and other search engines, saying the ads were misleading because they didn’t include risk information.

The warnings marked one of the first major actions by the FDA to crack down on Internet promotion, which is taking a bigger chunk of pharmaceutical marketing budgets because many people use search engines to find out about health problems.

The ads cited by the FDA typically come up as “sponsored links” when people type a disease name or product name into a search engine. Most of the world’s largest pharmaceutical companies were among the 14 that received FDA warning letters.

One letter went to Biogen Idec Inc. over its multiple sclerosis drug Tysabri.

The ads say “A Multiple Sclerosis Treatment That’s Different from the Others” or “Satisfied with your MS Medication or Looking for Something Different?” but don’t include any risk information, according to the FDA.

“Their casual approach to Tysabri treatment is extraordinary in light of the potentially lethal risks of the drug and the stringent controls over its distribution,” the FDA said in its letter to Biogen on March 26. The letter was posted on the agency’s Web site Friday.

Tysabri has been linked with a serious brain infection in several patients and is marketed under restrictions designed to reduce the risk of the side effect.

The company is working closely with the FDA to resolve the situation, said spokeswoman Naomi Aoki. She said the company takes its responsibility to communicate the risks and benefits of Tysabri “very seriously.”

Biogen’s ad includes a link to the Web site for the drug, which does contain the relevant risk information. The FDA said the link “does not mitigate the misleading omission of risk information from these promotional materials.”

Source: Various (06/04/09)

Biogen Idec Inc said on Wednesday it is developing a test that can identify the presence of a virus that can cause a potentially deadly brain infection in certain patients taking its multiple sclerosis drug Tysabri, and hopes to have it available by year-end.

Cecil Pickett, Biogen's head of research and development, said the company is working on an antibody-based test that can ascertain the presence in a patient's blood of the JC virus, which can cause progressive multifocal leukoencephalopathy, or PML.

Tysabri, which Biogen co-markets with Ireland's Elan Corp, is the biotech company's most important product with 2008 sales of $813 million. But sales have been hurt by the drug's association with PML.

It was withdrawn from the market in 2005 but reintroduced in July 2006 with stricter safety warnings as patients with the degenerative disease were willing to assume the risk given the drug's clear benefits over other treatments.

Tysabri not only delays progression of MS but in some cases has shown improvement of disability.

Last month, Biogen scaled back growth projections for the drug, conceding it will not meet its previous forecast of 100,000 patients on Tysabri by the end of 2010.

But Dr. Al Sandrock, Biogen's senior VP of neurology R&D, said the risk of developing PML appears to be less than originally believed.

Speaking at Biogen's R&D Day for analysts and investors, Sandrock said since Tysabri's reintroduction the PML rate is about 1 in 4,000 over 12 months of exposure. It was originally thought to be closer to 1 in 1,000.

Pickett said the company is placing a very high priority on developing the JC virus test, and hopes to have it available by the end of this year. But he said greater exposure to the virus does not necessarily predispose a patient to PML.

Other factors relating to a person's immune system or mutations in the virus could also be involved, he said.

"It is a complicated research program and we need to sort these things out before we give guidance," he said.

Five cases of PML have emerged in patients taking the drug since last July, and one has died.

Cambridge, Massachusetts-based Biogen emphasizes that patients who develop PML can now undergo a process called plasma exchange that removes Tysabri from their blood, meaning the disease is not necessarily fatal, which is helping give more confidence to physicians.

There have been suggestions that long-term Tysabri users stop taking the drug for a time -- a so-called drug holiday -- in order to reduce PML risk. Sandrock said Biogen is recommending against drug holidays as it likely decreases the drug's benefit and may not improve safety.

"Within months you get a return of disease activity," he said. 

Roughly 60 percent of physicians believe Tysabri's benefit outweigh its risk, Pickett said, down from 64 percent before the cases emerged in July. Still, data shows 74 percent of physicians expect to increase their use of the drug over the next six months.

Source: Reuters © Thomson Reuters 2009 (26/03/09)

A fifth confirmed case of progressive multifocal leukoencephalopathy, or PML has been reported to federal regulators.

The case, reported by Biogen Idec, Inc. on 6th February, occurred in a patient in Europe who had been taking Tysabri for 12 months.

Biogen Idec can confirm the patient was being treated with Tysabri as monotherapy for Multiple Sclerosis.

Biogen spokeswoman Amy Brockelman said the company was reviewing the case.

Source: Various (12/02/09)

A multiple sclerosis patient who developed a severe brain infection after taking Biogen Idec Inc. and Elan Corp.’s Tysabri, the fourth case reported in five months, has died, according to Biogen.

Cambridge, Massachusetts-based Biogen was informed of the American woman’s death two days ago, company spokeswoman Naomi Aoki said in an interview. The company reported on Oct. 29 that the patient had been diagnosed with the brain illness, progressive multifocal leukoencephalopathy.

Tysabri, which generated $597 million in sales in the first nine months of the year, is Biogen’s second-best-selling medicine after the MS drug Avonex. Biogen and its marketing partner, Irish drugmaker Elan, pulled Tysabri from the market in February 2005 after three patients, two of whom died, contracted PML. The death is the first among four cases of the brain illness reported since the drug was reintroduced in the U.S. in 2006.

The patient had received 14 Tysabri infusions before becoming ill, Biogen reported in a regulatory filing in October. Aoki declined to comment on the type of treatment for PML the patient received.

Since Tysabri’s reintroduction, three European patients have contracted PML. Biogen and Elan reported one case on Dec. 15 and two others on July 31. Elan fell 3 euro cents to 4.42 euros at 9:45 a.m. in Dublin trading.

More than 48,000 patients have taken Tysabri, Biogen told investors on Oct. 21, when the company released its earnings. Chief Executive Officer James Mullen said 100,000 patients will be taking the drug by 2010.

Affects 1 of 1,000

PML is included in Tysabri’s prescribing information as a possible side effect in 1 of every 1,000 patients taking the drug. The condition occurs when the JC virus, named with initials for the first patient diagnosed with it, evades the body’s immune defenses and penetrates the brain, causing irreversible damage.

The U.S. Food and Drug Administration approved Tysabri’s return to the market in June 2006 because research showed the treatment is twice as effective as other MS drugs. At the same time, the agency mandated strict measures to monitor side effects.

MS is a neurological disorder that robs people of muscle control and balance, sometimes leading to damaged vision and paralysis. The disease, which affects about 2.5 million people worldwide, is caused when the body’s immune system attacks the protective coating of nerve fibers.

Tysabri, given intravenously once a month, is designed to suppress the immune assault and is one of five immune-suppressing therapies that are known to cause PML. The others are Roche Holding AG’s CellCept, Biogen and Genentech Inc.’s Rituxan, Genzyme Corp.’s Campath and Genentech’s Raptiva.

Source: Bloomberg.com © 2008 Bloomberg L.P. (19/12/08)

Only around one in 10 of those who are eligible for a new drug to treat multiple sclerosis are getting it, even though it was approved a year ago for use in the NHS, the Guardian has been told.

Natalizumab, which goes by the brand name Tysabri, is the first drug that the National Institute for Clinical Excellence has approved for multiple sclerosis.

MS is a disease of the central nervous system which can progress from tingling and numbness of the limbs to blindness and paralysis. There is no cure, but the drug slows the progression of the disease in some of the most severe cases.

But in an answer to a parliamentary question put by the Liberal Democrat MP Paul Burstow, the government said between 100 and 300 people were getting the drug as of March this year, out of a possible 2,000 who could benefit from it.

"It is incredibly difficult to understand how, more than a year on from the Nice positive decision, treatment can still be withheld from eligible patients," said Dr Jayne Spink, director of policy and research at the MS Society.

Some delays may be due to the need to give the drug as an hour-long intravenous infusion, which means there must be a suitable place available.

Two women in West Yorkshire are still waiting to get Tysabri. Penny Copley, 42, was offered it by her consultant in July last year, but has not begun treatment. "It has been tested and proven and put on the register by Nice. What's the point of Nice doing that if the hospitals are not on board?" she said. Having multiple sclerosis "is not like the common cold", she said. "It's something I have got for life and I'm trying to better my life."

She and Ruth Penrose, 43, are members of an MS support group called Pins and Needles and are aware that some hospitals are offering Tysabri while their own, Pinderfields General hospital in Wakefield, has so far failed to treat them.

Primary care trusts have three months to implement Nice guidance, which would have run out in November last year, said Ms Penrose. "Nothing was done about it until Penny and I decided to write a letter to the PCT," she said. "Then they said they would implement Tysabri as soon as they had found a safe and sustainable environment."

The Department of Health said the choice of treatment was up to the clinician and patient. "The government has made it clear that the local NHS is required to provide funding for treatments and drugs recommended by Nice within three months of the Nice technology appraisal guidance being published," a spokesman said.

Source: guardian.co.uk © Guardian News and Media Limited 2008 (16/12/08)

Biotechnology companies Biogen Idec Inc. and Elan Corp. on Monday reported the fourth case this year of a deadly brain infection in a patient taking their multiple-sclerosis drug Tysabri.

The companies said they notified relevant regulatory agencies about the patient, located in the European Union, on Dec. 11. That patient has received about 26 months of Tysabri for the autoimmune condition multiple sclerosis and is being treated by a physician.

The drug has been facing pressure on the market since August, when the companies reported two new cases of the brain infection called progressive multifocal leukoencephalopathy, or PML. A third case was reported in November. More than 35,500 patients are taking the drug worldwide.

The companies have argued the risks, which are on the drug's label, are outweighed by the benefit the drug provides to multiple sclerosis patients. Tysabri was pulled from the market in 2005 after being linked to PML but reintroduced under restricted sales conditions in mid-2006.

Source: CNNMoney.com © 2008 Cable News Network.(15/12/08)

Drug developer Biogen Idec Inc. Wednesday reported in a regulatory filing that a multiple sclerosis patient who was being treated with the company's Tysabri in the commercial setting in the U.S. developed progressive multifocal leukoencephalopathy or PML.

According to the Cambridge, Massachusetts-based company, the diagnosis was made after a JC Virus DNA was detected in the cerebrospinal fluid in the setting of clinical signs, symptoms and magnetic resonance imaging findings consistent with the diagnosis of PML.

The company noted that the patient has a history of multiple sclerosis and prior disease modifying therapies, including beta-interferons and glatiramer acetate. The patient had also received prior therapy with methotrexate for a rheumatological condition and received 14 infusions of Tysabri monotherapy.

Biogen said clinical vigilance led to early identification of signs and symptoms of possible PML and to clinical evaluation that included MRI scanning and CSF testing. The patient is under the care of the treating physician.

Tysabri, marketed by Elan Corp Plc., was withdrawn from the market in 2005 after three patients developed brain infection. The drug re-emerged in 2006 with warnings after the FDA decided that MS patients ready to face the risks of the drug should have access to its benefits. The latest is the third case reported since July.

Last month Biogen and Elan said a post-hoc analysis of Tysabri, when compared to placebo over two years, showed sustained improvements in its functional outcome, rather then merely slowing or preventing progression of the disability.

Source: RTTNews.com (30/10)

Québec's Régie de l'assurance maladie du Québec (RAMQ) announced that effective October 1, 2008, Tysabri(TM) was added to its provincial formulary making Québec the first province in Canada to list the medication.

This treatment has been shown to reduce the frequency of clinical relapses, delay the progression of disability and decrease the number and volume of active brain lesions. It has been demonstrated to improve patient quality of life and results in some patients being completely free of disease activity.

"It's critical for doctors to be able to prescribe the appropriate
medications for the needs of individual patients, and today's decision by RAMQ allows us to continue doing this for people with MS," says Dr. François Jacques, Neurologist, MD FRCP, Director of the Clinique Neuro Outaouais. "Adding Tysabri(TM) to our arsenal of MS medications is wonderful news as it provides us with the opportunity to offer our patients the best available treatments for their disease with the ultimate goal of helping them to better manage their symptoms and overall health."

"Tysabri(TM) has proven scientific benefit and we are pleased that Québec patients will now have the option of choosing this therapy if their doctors deem it necessary for them," says Dr. Paul O'Connor, National Scientific and Clinical Advisor to the MS Society of Canada. "The Multiple Sclerosis Society is working towards the day that Canadians across the country will have equal access to treatments so that they too may benefit from the most appropriate medication for their condition."

Canada Lags Behind Other Developed Countries Worldwide

However, Canada still lags behind its global counterparts in making newer
medications available to Canadians who can benefit from them. In light of its recent ranking near the bottom of a list of developed countries in providing public access to new drug therapies by the 2007 Wyatt Health International Comparison Study, Canada currently remains the only developed country in the world not reimbursing the first new MS therapy in almost a decade.

This means that MS patients like Deirdre, who do not live in Québec and experience the financial burden of paying for her MS treatment out of their own pocket, often have no choice but to discontinue a therapy that has noticeably improved their condition and are forced to watch their health and quality of life decline.

"I was diagnosed with MS eight years ago and I can say unequivocally that Tysabri(TM) has significantly improved my quality of life," says Deirdre Carnegie. "I am able to take this therapy now because of my private insurance coverage, but that is not guaranteed. I am concerned that someday, I may not be able to access the medication I need. While I am pleased for people with MS in Québec, I am hoping that the rest of the provinces will join Québec in listing this medication on their formularies so no one has to worry about how they can obtain it and physicians can prescribe it to patients who will benefit most."

No two people with MS respond the same way to treatment. Despite where in Canada an MS patient lives, the more treatment choices available to patients like Deirdre and healthcare providers, the better able they are to select a therapy that will most effectively control the patient's symptoms and help delay disease progression.

Source: CNW Group (06/10/08)

The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended that the product information for Tysabri (natalizumab) be updated to further increase awareness about the risk of progressive multifocal leukoencephalopathy (PML) in patients with relapsing-remitting multiple sclerosis (MS) who have been treated with the medicine.

PML is a rare brain infection whose symptoms are similar to those of an MS attack. The CHMP's recommendation follows the reporting in July of two new cases of PML in patients who had been treated for MS with Tysabri alone for more than 12 months.

Following a review of the available data, the Committee concluded that the benefits of Tysabri continue to outweigh its risks in the treatment of relapsing-remitting MS, but that the existing warning on the risk of PML should be strengthened to heighten patients' and prescribers' awareness about this rare but serious side effect.

In addition, the Committee requested an update to the 'Physician Information and Management Guidelines for Multiple Sclerosis Patients on Tysabri'. These guidelines are part of the agreed risk management plan for Tysabri, which set out a series of risk minimisation measures. Following the update, doctors will be able to obtain more detailed guidance on how to differentiate PML from a relapse of MS, and how to manage suspected cases of PML.

The CHMP's recommendation will now be sent to the European Commission for the adoption of a decision.

Source: Medica lNews Today © 2008 MediLexicon International Ltd (26/09/08)

One of two European patients, who developed a potentially deadly brain infection after taking the multiple sclerosis drug Tysabri, is deteriorating and likely to suffer brain damage, according to a researcher involved in their care.

The other patient diagnosed with the infection in July is recovering, the researcher said.

The drug, made by Biogen Idec Inc and Elan Corp, was temporarily withdrawn from the market in 2005 after being linked with three cases of an often lethal infection known as progressive multifocal leukoencephalopathy, or PML.

Due to its advantages over older MS treatments and patient willingness to take on the risks, Tysabri was reintroduced with stricter warnings in 2006. No new cases were reported until the end of July, when Biogen announced that two patients had developed the infection.

Biogen said that no further new PML cases have been confirmed.

Dr. Ralf Gold of Ruhr University Bochum, Germany, said in an interview that a German patient, hospitalized near the town of Freiburg, is close to a coma and being fed through tubes, though he is breathing on his own.

The other patient, a 37-year-old Swede, is in a rehabilitation center near Stockholm and suffering only from mild weakness on one side of his body.

Gold said the 52-year-old German patient was not diagnosed until at least three months after developing the disease, whereas the Swedish patient's condition was identified in less than a month. As a result, the German patient had a higher level of the virus in his brain.

The two were treated through plasmapheresis, a procedure in which a patient's blood is removed, cleared of the drug, and replaced.

Gold presented an update on the two cases at the World Congress on Treatment and Research in Multiple Sclerosis in Montreal.

Investors have been watching the patients' progress to see whether PML can be reversed. They are also watching to see how many cases of the infection develop among patients taking the drug, which is considered a critically important growth driver for both companies.

Tysabri had second-quarter sales of $200 million, but its fortunes have been inextricably linked to PML concerns.

"The drug's strong efficacy profile should keep it as a preferred agent, in our opinion," Leerink Swann analyst William Tanner wrote in a research note.

In a report ahead of Gold's update, Geoff Porges, an analyst at Sanford Bernstein, said that if the disease becomes manageable through plasmapheresis then the impact of these cases will be blunted.

He said experts interviewed at the meeting have confirmed that in Europe and North America there are a number of patients with suspected PML whose physicians discontinued Tysabri use.

"We believe it is incumbent on Biogen to disclose this information to physicians in order for them to fully evaluate and disclose the risks associated with the product," he said.

Biogen spokeswoman Naomi Aoki said, "We have disclosed the only two cases of diagnosed PML that we have seen so far."

Gold added that while certain databases pick up cases in which a doctor suspects PML and discontinues Tysabri, the cases have not been confirmed either through an MRI or any other scientific measures.

Gold said the virus appears to be leaving the German patient's brain, but he is suffering from brain damage brought about by a condition known as immune reconstitution inflammatory syndrome, or IRIS. This occurs when the immune system, in eliminating an infection, produces an excessive inflammatory response that can worsen symptoms.

It is most likely the patient will be permanently brain damaged, Gold said. The only question is by how much.

The patient was started on a course of corticosteroids on Friday, the standard treatment for IRIS.

It typically becomes clear within a few days whether such a treatment is likely to work, Gold said. In the meantime, the patient is in a critical condition but not in intensive care. (Additional reporting by Bill Berkrot in New York, editing by Leslie Gevirtz)

Source: Forbes.com Copywrite 2008 Forbes.com LLC™ (21/09/08)

The FDA has begun posting a list of prescription drugs under investigation for potential safety problems in an effort to better inform doctors and patients.

The first list is a bare-bones compilation naming 20 medications and the potential issue for each. It provides no indication of how widespread or serious the problems might be, leading some consumer advocates to question its usefulness, and prompting industry worries that skittish patients might stop taking a useful medication if they see it listed.

Food and Drug Administration officials said they are trying to walk a fine line in being more open to the public while avoiding needless scares. Congress, in a drug safety bill passed in 2007, ordered the agency to post quarterly listings of medications under investigation.

"My message to patients is this: Don't stop taking your medicine," said Dr. Janet Woodcock, who heads the FDA's Center for Drug Evaluation and Research. "If your doctor has prescribed a drug that appears on this list, you should continue taking it unless your doctor advises you differently."

One emerging concern that previously got little attention involved Tysabri, a newer, widely used multiple sclerosis drug. The FDA said it is investigating a potential link to skin melanoma, a dangerous cancer. Doctors in Boston had reported two cases of melanoma in Tysabri patients in a letter to the New England Journal of Medicine in February. Tysabri suppresses the immune system, and it has also been linked to a rare kind of brain infection that is often fatal. Manufacturer Biogen Idec Inc. said it does not believe there is an increased risk of melanoma.

The FDA said drugs will be placed on the list based on reports it receives from hospitals, doctors and patients.

"What's new here is that we are telling the public really at the earliest stage what we are working on," said Dr. Gerald Dal Pan, head of the FDA's drug safety office. "I think the public told us, 'We want to know what you are working on.' And we are responding to that."

The list is not just a reflection of raw data, but more like what a police officer would call "probable cause." Officials said a drug will only be listed if FDA safety reviewers determine that a reported problem deserves a closer look.

"Our hope is that this list will serve not only as a means of communication to the public, but that it will also serve to encourage (medical) providers to provide us with additional reports should they see similar kinds of adverse events with the drugs that are on the list," said Dr. Paul Seligman, who is responsible for the FDA's safety communications.

Consumer advocates called the listing a positive step, but said it needs to be fleshed out.

"It's a good thing to get started but it needs to have much more detail if it's to have significant safety value," said Thomas J. Moore, a senior scientist with the Institute for Safe Medication Practices. "A table with just a few words of description is quite limited."

"It's just the most basic warning system," said Diana Zuckerman, president of the National Research Center for Women and Families. "It's not going to say how many reports there were. It's not going to say how many died and how many were hospitalized."

Nor is it clear how drugs suspected of a problem will be removed from the list if later exonerated.

The Pharmaceutical Research and Manufacturers of America, the main industry lobbying group, said it supports giving more safety information to doctors and patients, but worries that some will be needlessly alarmed.

"Our reservation is that patients will be abruptly stopping therapy," said Alan Goldhammer, a vice president of the organization. "One can't generalize with an emerging safety notice. It may affect half the patients, a quarter of the patients, or only a small subset of the patients."

Source: FDA and GoErie.com © 2008 CyberInk LP (08/09/08)

Two European patients who recently developed a dangerous brain infection after taking Elan's multiple sclerosis drug Tysabri are now recovering. Elan's shares rose sharply in Dublin on the news.

A researcher involved in their care told the Reuters news agency that one patient in Scandinavia was now out of danger while a second man in Germany was in the early recovery phase.

Ralf Gold of the Ruhr University Bochum was presenting an update on the cases at the annual meeting of the European Federation of Neurological Societies in Madrid.

Tysabri was withdrawn in 2005 amid three cases of PML, but returned to the market in 2006 with warnings and tougher prescription guidelines.

Source: RTÉ Business © RTÉ 2008 (27/08/08)

A warning on Biogen Idec and Elan Corp's drug, Tysabri, has been revised following two recent reports of a potentially fatal brain infection, Biogen said.

The company plans to provide an update on the two patients on today at a medical conference in Madrid, Biogen spokeswoman Shannon Altimari also said.

Still, both companies were down sharply since they disclosed on July 31 that two more patients had developed progressive multifocal leukoencephalopathy, a brain disorder known as PML that is usually fatal.

The FDA, in an alert to doctors posted on Monday on its website, said the agency had been told of the two newest PML cases and was "working with the manufacturer to amend the product labeling."

Biogen's Altimari said prescribing instructions were changed last week to note that PML had been reported in patients using Tysabri as their sole treatment for multiple sclerosis.

The two recent cases involved patients in Europe who were using Tysabri as "monotherapy," or stand-alone treatment, for more than a year.

"While the two patients who developed PML were on monotherapy, the FDA still believes that Tysabri monotherapy may confer a lower risk of PML than when Tysabri is used together with other immunomodulatory medications," the FDA said. Previously, PML had been seen in patients using Tysabri with other medicines to control MS. Tysabri was withdrawn in 2005 amid three cases of PML, but returned to the market in 2006 with warnings and tougher prescription guidelines.

New language on Tysabri's label notes that PML incidence "appears to be lower" with monotherapy, but adds "the number of cases is too few and the number of patients treated too small to reliably conclude that the true risk of PML is lower in patients treated with Tysabri alone."

The changes "were made with the FDA's concurrence," agency spokeswoman Sandy Walsh said late on Monday.

About 39,000 patients have been treated with Tysabri worldwide, with about 12,000 patients using the drug for at least a year, the FDA said.

Tysabri, known generically as natalizumab, is approved for treating multiple sclerosis and the bowel disorder Crohn's disease. It is given by injection.

Biogen plans to provide an update on the condition of the two patients with PML at the European Federation of Neurological Societies in Madrid on Tuesday, Altimari said.

Source: guardian.co.uk © Guardian News and Media Limited 2008 (26/08/08)

MedPredict, a global provider of pharmaceutical competitive intelligence and market research, has published a new report providing critical strategic insight for pharma and biotech companies with a stake in the market for multiple sclerosis (MS) therapies.

Biogen/Elan’s Tysabri has been under scrutiny due to two additional
reported cases of PML, a rare and potentially fatal brain disease
associated with use of the drug. MedPredict recently convened an expert
panel of neurologists to assess the significance of the PML cases, and the
effect on prescribing and development of new potent immunosurveillants.

“Nobody at the Thought Leader level was surprised that there were more new (PML) events,” according to Jeff Berk, MedPredict’s president. “At the time of the reinstatement of the US license for Tysabri, the FDA Advisory Committee stated that they expected there to be more events. Our panel discusses whether that sentiment will translate to community-based neurologists.”

The report also updates progress on other approaches to treatment of
MS, including:

– New interferons, integrin inhibitors, B-cell inhibitors, S1Ps,
fumarates, neuroprotection/neuroregeneration.

– The potential for vaccine or MAb approaches for the treatment or
prevention of multiple sclerosis.

– Which therapeutics in development to provide symptomatic benefits in
MS are the most likely winners.

MedPredict’s analysis also provides guidance for clinical trial design
in MS. “There have been a number of high-profile failed trials, both in
relapsing-remitting and in progressive MS,” said Dr. Berk. “The panel talks about strategies for improving the odds of success through better designs and better metrics.”

Companies and partnerships discussed in this report include: Acorda,
Amgen/Epix, Artielle ImmunoTherapeutics, Avanir, BaroFold, Bayhill,
Bayer-Schering, Bayer-Schering/Genzyme, Biogen, Biogen/Elan,
Biogen/Genentech/Roche, Biogen/UCB, Daiichi Sankyo, Genentech, GSK,
GSK/Genmab, GSK/Mitsubishi Tanabe, Lilly/BioMS, Merck, Merck-Serono, Novartis, Ono, Opexa, PDL/Biogen/Roche, Peptimmune, Roche/Actelion, Roche/Genentech, Sanofi-Aventis, Teva/Merck-Serono, Teva.

This report can be purchased by contacting MedPredict.

About MedPredict

MedPredict (http://www.medpredict.com) maintains a proprietary database
of over 1,000 global physician thought leaders, including 40+ specialties
in 30+ therapeutic categories. Based on primary interviews with these
thought leaders, MedPredict publishes periodic reports in each category to
keep clients up-to-date on emerging trends and competitive activity. The
reports include thought leader reactions to recent publications and medical
conferences, as well as clinical, regulatory and marketing activity.

Source:  MedPredict (21/08/08)

At the end of July 2008, the European Medicines Agency (EMEA) received two reports of progressive multifocal leukoencephalopathy (PML) in patients with relapsing-remitting multiple sclerosis (MS) who have been treated with Tysabri.

PML is a rare brain infection with symptoms that are similar to those of an MS attack. The two cases occurred in patients who have been treated for MS with Tysabri only for more than 12 months. The two cases were reported as part of the continuous safety-monitoring of medicines following their authorisation and placing on the market.

The risk of PML with Tysabri is known and is kept under close monitoring by the EMEA. The product information advises healthcare professionals that the medicine must not be used in patients who have PML and that patients taking Tysabri should be regularly monitored for signs and symptoms suggestive of PML.

The two cases are currently being assessed by the EMEA's scientific Committee for Medicinal Products for Human Use (CHMP). Elan, the marketing authorisation holder for Tysabri, has also been asked to provide any additional information they may have. Following assessment of all available data, the CHMP will determine whether any changes to the currently approved product information or the existing risk minimisation measures, including the 'Physician Information and Management Guidelines for Multiple Sclerosis Patients on Tysabri' are necessary.

Notes:

1. Tysabri is used to treat relapsing-remitting MS in patients with high disease activity despite treatment with a beta-interferon or whose disease is severe and progressing rapidly.

2. More information about Tysabri is available on the EMEA website.

3. The 'Physician Information and Management Guidelines for Multiple Sclerosis Patients on Tysabri' are part of the agreed risk management plan for Tysabri. In accordance with this plan, the marketing authorisation holder for Tysabri committed to provide an information pack to all physicians who intend to prescribe Tysabri. The pack contains, among other elements, also information about the diagnosis and management of PML. For more information see here.

Source: European Medicines Agency (14/08/08)

Biogen Idec Inc. and Elan Corp. reported two confirmed cases of a deadly brain infection in patients taking the multiple sclerosis drug Tysabri, the first since the drug was reintroduced in the U.S. in 2006.

The two patients were in the European Union, Biogen said today in a regulatory filing. The cases of the disease, progressive multifocal leukoencephalopathy, were confirmed this week, according to the company's statement.

Biogen and Elan voluntarily pulled the drug from the market in February 2005 after three patients unexpectedly contracted the disease, which caused two deaths. Tysabri was reintroduced in July 2006 in the U.S. and sold for the first time in the EU at the same time. One patient had been taking the drug for 17 months and the other took it for 14 months, Biogen said.

"This is going to be fairly disruptive to sales in the United States,'' said Mark J. Schoenebaum, an analyst with Deutsche Bank Securities in New York, by telephone. "There is a real fear of the unknown here, and I think some patients and physicians are going to take a drug holiday'' until the company discloses more details.

More than 31,800 multiple sclerosis patients use Tysabri, Biogen spokeswoman Naomi Aoki said. About 14,000 patients have taken Tysabri for more than a year, and 6,500 patients have taken it for 18 months or longer.

Anticipated Cases

"We've said ever since the reintroduction that we anticipate seeing additional cases,'' Aoki said today in a telephone interview. "Withdrawing the drug is not under consideration."

The condition was included in the prescribing information on the drug as a possible side effect in 1 of every 1,000 patients taking the drug, Aoki said. One patient is clinically stable and is at home, Biogen said. The other patient is hospitalized.

Goal of 100,000 Patients

On July 22, Biogen reported second-quarter net income rose 11 percent to $207 million on sales of Tysabri, its fastest- growing treatment. Biogen has estimated 100,000 patients will be taking Tysabri by 2010, a goal critical to the company's future growth, Thomas Weisel analyst Ian Somaiya said in a note to clients at the time.

Tysabri was approved in the U.S. in January to treat Crohn's disease, an inflammatory intestine and bowel disorder.

Source: Bloomberg.com © Bloomberg L.P. (01/08/08)

Specifically, as of the end of June 2008:
-- In the US, more than 17,800 patients are on TYSABRI commercially and more than 3,100 physicians have prescribed the therapy;

-- Outside of the US, nearly 13,400 patients are on TYSABRI commercially;

-- In global clinical trials, more than 600 patients are on TYSABRI; and,

-- There have been no confirmed cases of progressive multifocal leukoencephalopathy (PML) since re-launch in the US and the first international approval in July 2006.

Cumulatively, in the combined clinical trial and post-marketing settings:
-- More than 43,300 patients have been treated with TYSABRI; and

-- Of those patients, nearly 13,900 have received at least one year of TYSABRI therapy and approximately 6,600 patients have been on therapy for 18 months or longer.

"Since beginning TYSABRI therapy more than 18 months ago, I have experienced an improvement in my life and how I go about living with my MS every day," said patient Patricia Substelny. "The benefits have been significant in terms of reducing the number of exacerbations I have experienced. I can now confidently work in my garden, cook for my family and friends, and enjoy what life has to offer. I feel very fortunate to have TYSABRI as an option to help me manage my MS."

In the two years since reintroduction in the US and the first international approval, the data continue to demonstrate the benefits of TYSABRI treatment for patients with relapsing forms of MS. Data showed that TYSABRI treatment significantly increases the proportion of patients with MS considered to be disease free, according to post-hoc analyses of Phase III clinical trials presented at this year's American Academy of Neurology annual meeting. In addition, new data from a patient-reported outcomes survey was presented at the Consortium of Multiple Sclerosis Centers annual meeting showing that after only three months of treatment with TYSABRI, some patients reported improvements in overall quality of life, disease level, functional status and MS symptoms.

Along with TYSABRI's well-established clinical efficacy, growing health economic data from across the globe has been presented and published endorsing the pharmacoeconomic benefits of TYSABRI in MS patients. Based on this data, local health agencies in countries including Australia, Austria, the Netherlands, the United Kingdom, Sweden, France and Germany have all recommended TYSABRI for reimbursement by government-run health agencies.

"During the past two years, my patients who are being treated with TYSABRI appear to experience very positive benefits from the drug," said Dr. Thomas F. Scott, Professor of Neurology, Drexel University College of Medicine and Director, Allegheny MS Treatment Center in Pittsburgh. "Many of my patients tell me TYSABRI is helping them to regain control of their lives."

About TOUCH(TM), TYGRIS and CD INFORM

Before initiating treatment, all US patients, prescribers and infusion sites must be enrolled in the TOUCH Prescribing Program (TYSABRI Outreach: Unified Commitment to Health). TOUCH is designed to determine the incidence of and risk factors for serious opportunistic infections (OIs), including PML, and to monitor patients for signs and symptoms of PML while promoting informed benefit-risk discussions prior to initiating TYSABRI treatment. Physicians report on PML, other serious OIs, deaths and discontinuation of therapy on an ongoing basis.

TYGRIS (TYSABRI Global ObseRvation Program In Safety) and CD INFORM (Crohn's Disease - Investigating Natalizumab through Further Observational Research and Monitoring) are part of the global risk management plan for TYSABRI. TYGRIS is expected to enroll 5,000 MS patients worldwide, including approximately 2,000 - 2,500 patients from TOUCH. CD INFORM is expected to enroll 2,000 Crohn's patients in the US. Patients in TYGRIS and CD INFORM are evaluated at baseline and every six months thereafter for five years. Researchers will evaluate data including medical history; prior TYSABRI use; prior use of immunomodulatory, antineoplastic, or immunosuppressive agents; and all serious adverse events, including PML and other serious OIs and malignancies.

Adverse event reporting in the post-marketing setting is voluntary. It is possible that not all reactions have been reported, or that some reactions are not reported to Biogen Idec or Elan in a timely manner.

Source: SOURCE: Biogen Idec and Elan Corporation, plc (22/07/08)

An expensive drug that slows the progression of multiple sclerosis is one of several blockbuster medications to be subsidised for Australians from Tuesday.

About 2,300 people are expected to start using Tysabri to treat their condition in the first year of its listing on the Pharmaceutical Benefits Scheme (PBS).

The medication has been proven to reduce disease relapse and slow the disability progression in those with the most common, relapsing form of the incurable disease.

Unfunded, it cost each patient about $23,700.

Source: Yahoo 7 Copyright © 2008 Yahoo (01/07/08)

Biogen Idec, Elan and FDA notified healthcare professionals of reports of clinically significant liver injury, including markedly elevated serum hepatic enzymes and elevated total bilirubin, occurred as early as six days after the first dose of Tysabri. The combination of transaminase elevations and elevated bilirubin without evidence of obstruction is recognized as an important predictor of severe liver injury that may lead to death or the need for a liver transplant in some patients. Tysabri should be discontinued in patients with jaundice or other evidence of significant liver injury. Physicians should inform patients that Tysabri may cause liver injury.

Shannon Altimari, a Biogen spokeswoman, in a telephone interview said:

"Clinical trials that compared Tysabri to a placebo found a ``comparable'' rate of liver injury. The cases of liver injury have been reversible after patients stopped taking the medicine2, she said. "None of the patients with liver damage needed a transplant or died from the side effect."

In July, the FDA cited 28 cases of liver injury associated with Tysabri since November 2004, four of them potentially serious. Elan spokesman Andrew Lewis said at the time the cases were from "post-marketing experience.''

Many other drugs are linked to liver injury, and it's possible rare cases that wouldn't be spotted are being found with Tysabri because it is closely monitored for infection risk.

Various Sources(28/02/08)

Fresh hope is being offered to hundreds of Ulster multiple sclerosis sufferers today after the Government ruled that a promising new drug which could slow progression will be available within months.

Health Minister Michael McGimpsey has announced that Tysabri will be available to MS patients from April onwards.

MS is a relapsing or progressive disabling condition in which the body's immune system attacks the central nervous system, disrupting signals from the brain. Northern Ireland has the second highest rate of the disease in the world, slightly behind Scotland.

Tysabri is used in the treatment of severe 'relapsing remitting' MS - when a sufferer has more than two relapses in a year. Clinical trials have shown it can reduce the relapse rate by 67%. It reduced disability progression by 42% over a two year period.

The MS Society, which lobbied Mr McGimpsey to speed up the drug's availability here, said the development could potentially be prescribed to several hundred people in Northern Ireland. It has been available in the rest of the UK since last year.

Patricia Gordon, the charity's director, said the development marked the real benefit for people with MS since the return of power to Stormont last May.

"This new drug could make a real difference to hundreds of people with MS across Northern Ireland and the minister is to be congratulated in his efforts to help deliver its availability.

"Now that we've achieved the first real benefit for people with MS under devolution, we will be lobbying the minister to look at other areas which need to be addressed, such as the provision of physiotherapy," she said.

"We will be making a presentation to the minister about the fact that Northern Ireland has the second highest instance of MS per capita in the world, looking at ways of identifying the reasons for this terrible statistic and how the MS Society can work more closely with the department to address to help improve the lives of people with MS."

Mr McGimpsey made the announcement during a visit to the MS Society's headquarters.

"Tysabri has the potential to help people suffering from a particularly severe type of MS and I am therefore pleased to announce that the Department has endorsed the NICE guidance on the use of this drug," he said.

"Health and Social Services Boards and Trusts are preparing for the managed introduction of Tysabri so that patients can be assured of safe delivery and administration of this treatment."

"I know that... waiting times for these drugs had been unacceptably long. To address this, an additional £2m was invested over the last two years to ensure that by March this year, no patient eligible for disease modifying therapy should wait more than 13 weeks for their treatment to commence. I am confident that this target will be met."

Source: Belfast Telegraph © Independent News & Media (NI) (12/02/08)

Two multiple sclerosis patients developed malignant melanoma -- a deadly form of skin cancer -- soon after starting treatment with Tysabri.

Tysabri slows the self-destructive immune responses that attack the nervous systems of people with MS. In animal studies, these same immune responses hold melanoma in check. Might the drug have caused melanoma in these two MS patients?

It's possible, says Timothy K. Vartanian, MD, PhD, chief of the multiple sclerosis division at Beth Israel Deaconess Hospital and associate professor of neurology at Harvard Medical School. Vartanian and colleagues report the two cases in a letter to the Feb. 7 issue of The New England Journal of Medicine.

"The important thing to remember is that Tysabri remains by far the most effective FDA-approved drug for treating relapsing forms of MS," Vartanian tells WebMD. "There are adverse effects associated with all medications. For Tysabri, we now consider melanoma a potential additional risk."

Both of the women treated by Vartanian and colleagues had existing moles that became malignant after they started Tysabri treatment. The first patient, a 46-year-old woman, had had a mole on her shoulder for a long time.

"Shortly after her first infusion of Tysabri, we noticed a rapid change in the mole," Vartanian says. "It was found to be malignant melanoma with metastatic spread to her regional lymph nodes. Since that time she has relapsed with widely metastatic disease."

The second patient, a 45-year-old woman, had a mole on the back of her eye. Her doctors had monitored this mole for years, as MS patients undergo regular eye exams. The mole had been stable and unchanged since 1999. However, the woman had a family history of melanoma. Her father and a brother had melanomas; both of them remain alive and well.

"After several infusions of Tysabri, this mole dramatically changed in size, depth, and pigment and was identified to be an ocular melanoma," Vartanian says. "So we have two patients who, after relatively few doses of Tysabri, developed malignant melanoma."

One other MS patient also developed melanoma -- a man who received the treatment in clinical trials prior to the drug's FDA approval, confirms Shannon Altimari, a spokesperson for Biogen Idec Inc., which in partnership with Elan Corp. markets Tysabri.

"We did see a single case of melanoma in a male patient with a skin lesion present at first dose during Tysabri clinical trials," Altimari tells WebMD. "So everything written in this report is consistent with our clinical trial experience. We are fortunate to have a safety program in place to monitor for adverse events."

Even so, there's not yet enough evidence to convict Tysabri of causing melanoma, says Patricia O'Looney, MD, vice president for biomedical research at the National Multiple Sclerosis Society.

"From these two cases, one cannot draw the conclusion there is an association or link between Tysabri and melanoma," O'Looney tells WebMD. "There is a concern because it came so close to the dosing, but it is still too early to make any conclusion."

O'Looney notes that Tysabri is not a first-line treatment for MS -- it's usually given when MS gets worse despite some other treatment.

"So it is a balancing act to try to help a patient whose disease is getting worse and worse and to balance this against the possible risk identified in these two patients with melanoma," she says. "It is too early to even make a judgment of whether or not to give Tysabri to a patient with a family history of melanoma. The thing to do is to be aware of this possible risk and to go forward with caution."

Vartanian says it's his opinion that Tysabri's label should warn doctors and patients of the possible risk of melanoma in patients with atypical moles or a family history of melanoma. Altimari says the drug's makers have no current plans to do this.

Vartanian is asking all his MS patients to undergo a full skin survey by a dermatologist before starting Tysabri treatment, and every six months thereafter. But he's not going to refuse the drug to MS patients who need it.

"It is a small risk at this time, but in my opinion it is important for neurologists treating MS to get a dermatologist involved before starting Tysabri so that patient remains at low risk," he says.

WebMD  © 2008 WebMD, LLC.(07/02/08)

Elan Pharmaceuticals and Biogen Idec have said safety data continues to support the treatment of Multiple Sclerosis (MS) with Tysabri.

The company said more than 21,000 patients were on commercial and clinical Tysabri therapy worldwide as of late-December 2007.

Tysabri is a treatment approved for relapsing forms of MS in the US and relapsing-remitting MS in the European Union.

According to data available to the companies as of late December 2007:

-- In the US, approximately 12,900 patients were on Tysabri therapy commercially and approximately 2,500 physicians have prescribed the therapy;

-- Internationally, approximately 7,500 patients were on Tysabri therapy commercially;

-- In global clinical trials, approximately 700 patients were on Tysabri therapy; and

-- There have been no cases of progressive multifocal leukoencephalopathy (PML) since re-launch in the US and launch internationally in July 2006.

Source: Ireland.com © 2008 ireland.com (07/01/08)

A new drug, recently approved for use in New Zealand, has been heralded by one of the country’s leading experts as a “substantial step forward” in the treatment of a debilitating disease.

Tysabri® is a treatment for relapsing remitting multiple sclerosis (MS), a chronic and unpredictable disease of the central nervous system (CNS).

Dr Ernest Willoughby, a neurologist at Auckland City Hospital, is in charge of a trial of Tysabri in Auckland, involving five patients with MS.

Dr Willoughby says Tysabri is one of the biggest advances in MS treatment yet, and has sparked considerable interest among neurologists.

“It has the potential to help everyone with relapsing remitting MS,” he says.

In MS, patches of inflammation in the brain of spinal cord mean electrical impulses cannot be conducted to and from the brain, leading to the symptoms of MS. There is no known cure.

Relapsing remitting MS is the most common form of the disease. Patients experience episodes of increased symptoms, lasting several weeks or months, followed by a remission where the symptoms disappear or reduce.

Data, published in the New England Journal of Medicine, shows that over two years Tysabri treatment reduced relapses by 68% and reduced disability progression by 42%.

Other treatments such as beta-interferon and glatiramer acetate reduce relapses by around one third.

According to Dr Willoughby, neurologists in New Zealand already have restricted access to MS treatment compared to other western countries, and if Tysabri is not funded there is a risk of the country falling even further behind.

“In New Zealand, to qualify for treatment, it is necessary to have frequent relapses and moderate residual disability, so most people early in the course do not qualify."

Dr Willoughby says it is now widely accepted that starting patients on treatment early offers the best chance to prevent patients with relapsing remitting MS from progressing to the most disabling form of the disease - secondary progressive MS.

About 50% of patients with relapsing remitting MS develop secondary progressive MS within 10 to 20 years.

Although there is controversy concerning how the residual damage from relapses relates to the gradual decline in the secondary progressive phase, the belief is that by cutting the number of relapses, Tysabri could help prevent MS worsening later in the course.

However, it cannot fix damage which is already done –highlighting the need for early treatment.

While Tysabri was approved by Medsafe in September (2007), the issue of funding the drug is complex.

Unfunded, a patient would have to pay about $41,000 a year for treatment, a financial burden very few could even consider.

Dr Willoughby says: “Funding is a complicated process. Tysabri is an infused drug, which would normally be given in a hospital setting, and we’re currently looking at the issue that the treatment may be potentially approvable by individual DHBs or hospitals.”

His concern is that, if it is up to individual hospitals to decide whether to fund the drug, and what criteria to place on its use, we will end up with the situation where treatment for MS patients will vary, depending on where they live.

In a bid to prevent this, he says a group of interested neurologists has discussed making an approach to all DHBs in New Zealand to provide limited access to treatment with Tysabri.

However, this in itself is complicated and time-consuming, with each hospital having its own particular processes to go through in such situations.

“We’ve no idea how it will go. But we think it’s appropriate to try and get a consistent national policy on this, which may be difficult.”

Source: Sccop Health (19/11/07)

The Irish company owns a 50 percent stake in Tysabri along with Cambridge, Mass.-based Biogen Idec, which said that it is exploring a possible sale of the company after a number of inquiries from potential suitors.

Biogen manufactures Tysabri for sale in the United States at a facility in Research Triangle Park, where the company employs 750 people. It also makes another multiple sclerosis drug, Avonex, at the RTP facility.

Elan filed a document with regulators, according to The Financial Times, disclosing that it has hired a consultant to explore its options on the drug if Biogen Idec gets sold.

Elan could gain full ownership of the drug buy paying for Biogen's share at fair market rates. But it may also contemplate selling its share to whomever buys Biogen Idec.

Elan could also keep the co-marketing deal in place, regardless of whoever the new owner is.

Tysabri had initially become a blockbuster before it was pulled from the U.S. market two years ago following safety concerns. The drug returned to the marketplace in 2006 under stricter safety guidelines.

Both Biogen and Elan are trying to broaden Tysabri's indication for use in patients with Crohn's disease, a gastrointestinal disorder. The Food and Drug Administration recently extended its review of Tysabri for Crohn's by three months.

Source: Triangle Business Journal © 2007 American City Business Journals, Inc.(17/10/07)

Cambridge, Massachusetts-based Biogen and Ireland-based Elan released the data ahead of a presentation at the Congress of the European Committee for Treatment and Research in Multiple Sclerosis in Prague.

The companies said about 17,000 patients are taking Tysabri in the United States and Europe. Of those, 1,000 are in clinical trials.

Tysabri was taken off the market in 2005 after being linked with three cases of progressive multifocal leukoencephalopathy, or PML. The U.S. Food and Drug Administration allowed the drug back last July because it is effective and patients asked for it to be returned.

Tysabri is available in the United States through a safety-monitoring program known as TOUCH. All prescribers, infusion sites and patients are required to enroll in the program, which is designed to monitor patients for any signs or symptoms of PML.

The longer time goes by with no new cases of PML, the more comfortable doctors are in prescribing it.

Source: Reuters © Reuters2007All rights reserved (12/10/07)

The registration was based on a submission that included TYSABRI two-year Phase III clinical trial data and findings from a comprehensive safety evaluation. An estimated 4000 people in New Zealand are affected by MS.

“Today marks an important step forward for the New Zealand MS patient community,” said Eric Fidelin, Managing Director of Biogen Idec New Zealand. “TYSABRI represents one of the most significant advances in MS treatment in nearly 10 years and provides patients living with this disabling disease an important new therapeutic choice.”

Source: Biogen Idec NZ Limited and Elan Corporation, plc (30/09/07)

A drug watchdog is today set to reverse its decision on a key drug for multiple sclerosis (MS) patients, making it available to hundreds on the NHS.

Last year, the Scottish Medicines Consortium (SMC) said Tysabri was not cost-effective for use in the health service, leaving campaigners and patients devastated.

But after a new review of the treatment, the SMC is expected to announce it will be available on the NHS.

The move brings Scotland into line with England and Wales, where Tysabri was approved by officials last month.

The drug - which costs about £15,000 a year per patient - is designed for those with an aggressive form of MS which leads to disabling relapses. It will mostly be reserved for use in patients who have failed to respond to other treatments.

It is thought that some 400 patients a year in Scotland could receive the treatment. So far, only a handful have benefited from the drug.

The SMC's decision to reject Tysabri last December led to dismay among campaigners.

JK Rowling, the Harry Potter author whose mother suffered MS, made an impassioned plea to the SMC to reconsider its position. She said treatments should not be ruled out due to cost alone.

The expected about-turn was warmly welcomed by campaigners.

Mark Hazelwood, the director of the MS Society Scotland, said Tysabri was a "vital treatment option".

"A change in the advice given to NHS Scotland on Tysabri will be a massive victory for people with MS in Scotland," he said.

Mr Hazelwood said Tysabri was being used by more than 14,000 people worldwide.

"Major clinical trials have demonstrated that it can significantly reduce the relapse rate for people with severe remitting MS and also reduce the risk of disability progression," he said. "No other drug has shown the same potential to reduce disability for people with this form of MS, and its impact on the lives of the people receiving the treatment and their families can be considerable."

Dr Belinda Weller, a neurologist at the Western General Hospital in Edinburgh, also welcomed the decision. She said: "As a clinician, to have another treatment available for me to use in my patients is excellent news.

"This drug is especially important in treating patients who have the most severe forms of MS, where previously treatment options have been limited.

"I hope health boards will be ready to fund this treatment for the patients who will benefit from it."

Fiona Burns, an MS patient from Edinburgh, said: "Obviously, this is brilliant news. Hopefully, I will never need to take Tysabri. I am taking beta interferon at the moment, and it is working well. But it is good to know that this drug is there for people in Scotland.

"It was always my wish that they would make it more widely available."

'ABLE TO THINK OF THE FUTURE'

Daniel was a typical teenager who enjoyed going out with his friends and was studying for his exams when he was suddenly struck with multiple sclerosis last November.

His life was turned upside down - he could not go to school and his mother had to stop work to look after him.

But in March this year The Scotsman revealed that the 16-year-old was to start taking Tysabri after being given special permission by NHS Lothian.

At the time the teenager from East Lothian was having to use a wheelchair and wear an eye patch, because of the severity of his illness.

But after five months on the treatment, his parents cannot believe the change they have seen in Daniel.

His mother, Aileen, said: "He is doing really well.

"He is back at school and is now looking to the future and going to university to study architecture.

"I would say he is about 90 per cent better. Sometimes he is a bit clumsy and a bit wobbly, but so much better than he was before, you would hardly notice it.

"I think the drug has stopped any more relapses and he is actually able to think about the future now."

Daniel's stepfather, Peter, said doctors had told the family that Daniel should stay on Tysabri until even better treatments were developed.

"He has to go to hospital to be given the drug once a month, but he is going great. It seems that the treatment is doing the trick," he said.

Source: The Scotsman ©2007 Scotsman.com (10/09/07)

The drug is called Tysabri, and is a monoclonal antibody that affects the actions of the body's immune system. It is used in treating relapsing forms of Multiple Sclerosis, but also has certain side effects, increasing the risk of serious viral infection of the brain, which might lead to disability or death, so it is not appropriate for all patients.

“There are two groups of patients who will be entitled to take this drug for free,” says Dr Marios Pantzarides from the Institute of Neurology and Genetics. “The first group includes the patients who have regular, frequent attacks and already take an interferon injection and do not respond to it. They need to prove that the medicines they are taking do not help them, and meet the necessary medical criteria,” he said.

In the second group, we included all the new patients, who have had more than two, rather aggressive attacks within the previous months, and who don’t take any injections yet.”

Only those doctors who have completed a special Tysabri training will be deciding if the patient’s condition is appropriate to be included in the programme. “We already have 25 patients on the waiting list, but certainly there will be more patients accepted to the programme,” said Pantzarides.

Anthos Shekeris, 36, was diagnosed in 1999. “I have heard about this medicine,” he said, “and soon I am going to see my doctor and check if I meet the criteria.

“These medicines are very expensive, the cost of the drugs I am taking every month is £800, and without the government’s support, it would be really hard to cope,” he added.

Shekeris said MS patients in Cyprus also needed better support: “I believe there is not enough psychological support, especially for patients living in the villages. There are associations for MS patients only in Nicosia and Larnaca.
“I was really lucky being at Intercollege at the time I got sick, so I got the support I needed,” said Shekeris.

“There are 450 members in our association,” said Lenia Takoushi Christoforou, the head of the Multiple Sclerosis Association. “We are supporting them with physiotherapy, giving psychological help, and advising on legal procedures, like filling the forms when they apply for government support.”

But the number of members of association is only a fraction of the actual MS victims in Cyprus. Dr Pantzarides estimates there are 850 to 900 people affected by the condition in Cyprus.

Source: Cyprus Mail Copyright © Cyprus Mail 2007 (08/09/07)

Biogen Idec Says Still No New Cases of Rare Brain Disorder Reported in Tysabri Patients.

Biotechnology company Biogen Idec Inc. said Tuesday there have been no new reports of patients taking the multiple sclerosis drug Tysabri developing a rare and incurable nervous system disease.

The company claims data showing the lack of cases as of mid-July. Prior to that, the company said there were no new reports as of May 23.

Biogen withdrew Tysabri in February 2005 after two patients in clinical trials died of the condition, called progressive multifocal leukoencephalopathy, or PML.

Tysabri is codeveloped with Elan Corp. Patients taking the drug have to register with a program in order for the drug's safety to continue to be tracked. Earlier this month, a Food and Drug Administration panel recommended the drug be approved to also treat Crohn's disease, an intestinal disorder.

Through mid-July, the company said, about 14,000 people worldwide were taking the drug.

Source: Biogen Idec Inc (29/08/07)

Andrew Dillon, Executive Lead for the appraisal said:

"Having considered the evidence presented on the use of natalizumab for the treatment of multiple sclerosis within its licensed indications, along with responses received during the consultation, the independent advisory committee decided that natalizumab should be an option for the treatment only of rapidly evolving severe relapsing–remitting  multiple sclerosis. This guidance is good news for people with this particular severe form of multiple sclerosis."

Notes:

About the guidance

1. Rapidly evolving severe relapsing–remitting multiple sclerosis (RES) is defined by two or more disabling relapses in 1 year, and one or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous MRI.

About NICE

2. The National Institute for Health and Clinical Excellence (NICE) is the independent organisation responsible for providing national guidance on the promotion of good health and the prevention and treatment of ill health.

3. NICE produces guidance in three areas of health:

• public health – guidance on the promotion of good health and the prevention of ill health for those working in the NHS, local authorities and the wider public and voluntary sector
• health technologies – guidance on the use of new and existing medicines, treatments and procedures within the NHS
• clinical practice – guidance on the appropriate treatment and care of people with specific diseases and conditions within the NHS.

Source: NICE (22/08/07)

One year following its return to market in the US and introduction in the European Union, the companies estimate that as of mid-July 2007 in both commercial use and clinical trials approximately 14,000 patients are currently on TYSABRI therapy worldwide.

As of mid-July 2007:

• In the US, over 8,600 patients are on TYSABRI commercially and over 1,800 physicians have prescribed the therapy;
• In the EU, over 4,300 patients are on TYSABRI therapy commercially;
• In global clinical trials, approximately 1,000 patients are on TYSABRI therapy.

“Over the past year I have seen my patients benefit greatly from TYSABRI. As expected from clinical trials, TYSABRI is having a positive impact on their lives. The compelling efficacy of TYSABRI offers MS patients hope in the management of their disease,” said Dr. Howard Rossman, Medical Director, MS Center, Michigan Institute for Neurological Disorders in Farmington Hills, Michigan, and Clinical Professor of Neurology at Michigan State University. “Increased experience with TYSABRI will continue to inform us and contribute to our understanding of the important role of this therapy for people living with MS.”

“TYSABRI has had an incredible effect, and the improvements I have experienced are very real. I understand there are important risks to this therapy, but the benefits of TYSABRI were far too important for my family and me to overlook,” said TYSABRI patient, Mike Lynch.

In July 2006, TYSABRI was reintroduced in the US under the TOUCH Prescribing Program, a restricted distribution program, and was also introduced in the EU under a risk management plan. These programs were developed due to the increased risk of progressive multifocal leukoencephalopathy (PML), an opportunistic viral infection of the brain that usually leads to death or severe disability.

TYSABRI is a treatment approved for relapsing forms of MS in the US and relapsing-remitting MS in the European Union. According to data that have been published in the New England Journal of Medicine, after two years, TYSABRI treatment led to a 68% relative reduction (p<0.001) in the annualised relapse rate compared to placebo and reduced the relative risk of disability progression by 42-54% (p<0.001).

TYSABRI increases the risk of PML. Other serious adverse events that have occurred in TYSABRI-treated patients included hypersensitivity reactions (e.g., anaphylaxis), infections, depression and gallstones. Serious opportunistic and other atypical infections have been observed in TYSABRI-treated patients, some of whom were receiving concurrent immunosuppressants. Herpes infections were slightly more common in patients treated with TYSABRI.

In MS trials, the incidence and rate of other serious and common adverse events, including the overall incidence and rate of infections, were balanced between treatment groups. Common adverse events reported in TYSABRI-treated patients include headache, fatigue, infusion reactions, urinary tract infections, joint and limb pain, lower respiratory infections, rash, gastroenteritis, abdominal discomfort, vaginitis, and diarrhea.

TYSABRI is approved in the United States, European Union, Switzerland, Canada, Australia and Israel. TYSABRI was discovered by Elan and is co-developed with Biogen Idec.

Source: Finfacts Ireland © Copyright 2007 by Finfacts.com (23/07/07)

The national drugs watchdog has agreed to reconsider a ban on NHS prescribing of the drug Tysabri.

More than 10,000 Scots have MS, which destroys nerves and can kill when it reaches an advanced stage.

One form of the illness, relapsing remitting MS, causes flare-ups in the condition that can leave sufferers disabled for weeks before receding.

However, Tysabri can massively reduce the number of relapses and the damage they cause.

The National Institute for Clinical Excellence (Nice) recently ruled patients elsewhere in the UK could receive the drug.

But despite Scotland having the highest rates of MS in the world, patients can't get the drug after the Scottish Medicines Consortium rejected it, saying it was too expensive at nearly £15,000 a year.

Conventional but less effective treatments cost about half that figure.

However, the SMC is reconsidering its decision in a move which could help 600 patients with the most aggressive form of MS.

A spokesman said last year's rejection was not based purely on price but on balancing the extra cost of the drug against the extra benefits of it.

But today he confirmed: "We are looking at Tysabri again, following a revised submission from the drug company. We expect to make a decision in September."

Drugs firm Biogen has submitted new information on the drug and argues it can cut the number of relapses patients suffer by 68%.

Biogen also claims the drug can reduce further disability by 54%.

The MS Society in Scotland welcomed the latest review of the drug.

A spokesman for the charity said: "We recognise this is not a cheap therapy but the signs from clinical trials are that it will be twice as effective.

"At the moment there is little or no effective treatment available for people with a really aggressive form of relapsing-remitting MS, which affects around 600 people in Scotland."

Only those patients who have two disabling relapses in a year and a scan which shows brain or nerve damage are eligible for the new drug.

Source: Evening Times Online Copyright © 2007 Newsquest (Herald & Times) Limited. All Rights Reserved (14/07/07)

Biogen Idec and Elan Corporation welcome today’s announcement by the National Institute for Health and Clinical Excellence (NICE) in the final appraisal determination which recommended use of TYSABRI® (natalizumab) in people with highly active relapsing remitting multiple sclerosis (RRMS). TYSABRI is the first treatment for multiple sclerosis to be recommended for use by NICE.

“This decision offers people with highly active relapsing remitting multiple sclerosis hope of regaining control of their disease,” commented Professor Gavin Giovannoni, The Royal London Hospital. “TYSABRI represents a significant advance in MS treatment, offering real hope of delaying the progression of disability and reducing the frequency of relapses.”

Highly active RRMS (defined as two or more disabling relapses in one year and an active MRI scan) has a devastating effect on the lives of the individual and their families. These patients experience more relapses and will become disabled more quickly than those people with typical RRMS. This inevitably means that they will not be able to enjoy an active life combined with the strong probability that they, and the family members who care for them, will be unable to work. In these patients, MS progresses twice as quickly as those with less active forms of the disease.

TYSABRI is the first treatment to be specifically licensed for highly active RRMS. Over two years, treatment with TYSABRI leads to a 68% relative reduction in clinical relapses and a 54% relative reduction in the risk of sustained disability progression compared with placebo.

Hans Peter Hasler, Head of Biogen Idec International, added, “Multiple sclerosis can be a devastating condition if not treated appropriately, and we are very pleased that NICE has recommended in the final appraisal determination that patients with highly active relapsing remitting multiple sclerosis should have access to treatments like TYSABRI. With successful treatment with TYSABRI, highly active relapsing remitting multiple sclerosis patients are more likely to be able to continue to work, maintain active social lives, and spend quality time with their families.”

“TYSABRI is the first treatment to be recommended for use by NICE, a significant milestone for patients suffering from MS. This final appraisal firmly supports patients and their physicians having access to TYSABRI with its compelling benefits in the treatment of MS,” said Dr. Menghis Bairu, SVP, Head of Elan International.

As of late May, TYSABRI is already offering hope to approximately 12,000 patients on therapy in both commercial use and clinical trials in the US, Germany, France, Ireland and many other countries.

Source: Biogen Idec and Elan Corporation (03/07/07)

Under a Pharmaceutical Benefits Scheme ruling, people with MS will miss out on the drug, Tysabri, unless they can pay more than $30,000 a year when it becomes available in Australia in a few months.

A Pharmaceutical Benefits Advisory Committee review late last year conceded the drug was “the first additional effective treatment option in several years for this distressing condition” and “demonstrated a clinical benefit”.

But it concluded that its cost-effectiveness was not good enough and uncertain.

It estimated the drug would cost the Commonwealth at least $10 million in its first year, rising to $30-$40 million a year within five years.

But Multiple Sclerosis Society of WA chief executive Marcus Stafford said that while other drugs were used regularly to treat MS, it was clear Tysabri should be listed on the PBS.

He estimated at least 300 West Australians with MS could potentially benefit from the drug, a form of immuno-therapy.

Mr Stafford said the drug cut by 70 per cent the chances of people having a further attack and reduced the progression of the disability.

“The drug will be available for people but they’ll have to pay $2700 a month to get it and I don’t think there will be that many people who have a lazy $2700 net a month to pay for this, let alone the people who have a progressive disability,” he said.

“This is a shocking situation that we have people whose health would be significantly better in a relatively short period of time if we were farsighted enough to have this drug approved on the PBS.”

Kathy Balt, a 41-year-old married mother of two children aged 10 and 13, said the drug was her lifeline to retaining the limited mobility she had left.

Confined to a wheelchair, she works full-time for the Water Corporation in Northam but is worried that she could lose her sight and the use of her arms.

“I can’t tolerate any of the other disease-modifying drugs so that leaves me in a very vulnerable position,” she said.

“I don’t hold on to hope of being able to get out of my wheelchair.

“I’ve learnt to be disabled and accept that I can’t walk, but let’s not go blind and be forced out of the workforce too.”

Source: thewest.com.au West Australian Newspapers Limited 2007. All Rights Reserved(30/05/07)

Natalizumab has recently been re-approved by the FDA, and a comprehensive article published in the latest issue of CNS Drug Reviews provides a timely overview of the drug, its pharmacological properties, clinical efficacy, safety and toxicology.

MS is a disorder that affects the central nervous system, with leukocytes (inflammatory cells) attacking the body's neurons and causing serious damage. A highly effective immunosuppressive treatment, natalizumab is an antibody that prevents leukocytes from crossing blood vessel walls into tissues such as the brain and spinal cord. The drug may also benefit secondary lymphoid organs, such as lymph nodes and the spleen, and inhibit reactivation in the central nervous system. It has been shown to significantly reduce leukocyte cell numbers in spinal fluid, with benefits continuing for six months after treatment.

"The release of natalizumab ushers in a new era in the treatment of MS," says Dr. Olaf St've , author of the study, noting, however, that while the short-term risk-benefit ratio appears positive, the long-term risks remain unknown. "As therapy with natalizumab resumes worldwide, the neurologic community will garner more information about the long-term risks and benefits of this powerful therapeutic medication," but for now natalizumab use is being strictly monitored.

Both the FDA and TOUCH, a special distribution program designed to prevent patients not qualified for the treatment from receiving the drug, are working to make sure that any potential infectious complications are identified as early as possible.

News-medical.net(29/05/07)

They cite a number of controversial rulings by the National Institute for Health and Clinical Excellence (NICE), the body that decides which drugs should be available for NHS use.

Among drugs rejected by NICE is Tysabri, which substantially reduces the chance of relapses in multiple sclerosis patients.

One sufferer, Lesley Seddon, a GP and mother of three from Hounslow, west London, wants her NHS trust to allow her to switch to the drug because of the severe side effects of her present treatment regime.

Tysabri costs £20,000 a year, but Mrs Seddon said: "As a doctor I am careful about spending NHS money, but I am a patient, too. I know I am not going to be cured but this would give me a far better quality of life."

In written evidence to an inquiry into NICE by the Commons health select committee, the MS Society, the Alzheimer's Society and Bowel Cancer UK say the system is "inhumane".

Next month, the High Court is due to hear a challenge to NICE's rejection of three drugs, Aricept, Reminyl and Exelon, which slow the effects of memory loss in Alzheimer's sufferers.

The drugs cost just £2.50 a day, but NICE ruled that they made only a "moderate" difference to those with early or late Alzheimer's.

Andrew Dillon, NICE's chief executive, said it was impossible to come up with a perfect formula, but he insisted that the decision process took into account factors such as how far drugs reduced pain and improved mobility, as well as increasing length of life.

Source: Telegraph.co.uk © Copyright of Telegraph Media Group Limited 2007. (14/05/07)

Based on data from clinical trials and the cost of Tysabri, NICE has advised that the efficacy of Tysabri is not proven or that the cost is simply too much.

NICE has said that people currently receiving Tysabri (natalizumab) should have the option to continue therapy until they and their clinicians consider it appropriate to stop.

NICE has only allowed only 15 working days for public consultation on this decision, despite its own guidelines stating that four weeks are allowed.  (03/04/07)

PHARMACOLOGY
Natalizumab is a monoclonal antibody thought to act by inhibiting the migration of leukocytes into the central nervous system leading to a reduction of inflammation and demyelination.

CLINICAL STUDIES
The efficacy of natalizumab monotherapy was assessed in a two-year study¹ involving 942 patients with relapsing multiple sclerosis who had experienced at least one clinical relapse in the previous 12 months and scored between 0 and 5 on the Kurtzke Expanded Disability Status Scale (EDSS).

Patients received treatment by intravenous infusion every four weeks for more than two years; 627 patients were randomly assigned to the natalizumab group (300mg) and 315 to the placebo group. The study evaluated the rate of clinical relapse at one and two years and the rate of sustained progression of disability, using EDSS, at two years.

After two years of treatment there was a relative risk reduction in the rate of relapse of 68 per cent for patients treated with natalizumab compared to placebo. The risk of sustained disability progression (for 24 weeks) was reduced by 54 per cent in patients treated with natalizumab compared to placebo.² Natalizumab also showed significant effects on secondary end points, including a 92 per cent reduction in gadolinium enhancing lesions.¹

Overall adverse events were similar between the placebo and treatment groups. However, fatigue and allergic reactions were significantly more common with natalizumab compared to placebo.

¹. Polman C, Paul M, O'Connor W et al. A randomised, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. NEJM 2006: Vol 354(9); 899–910. ². Tysabri Summary of Product Characteristics. Biogen Idec Nov 2007.

Source: Healthcarerepublic (02/4/07)

Thousands of multiple sclerosis patients fear the most effective drug ever developed against the disease will be blocked by the Government's medicines watchdog.

Trials show Tysabri is twice as effective as other treatments available on the NHS. The problem is the fact that it can cost as much as £30,000 a year for each patient.

Medicines regulator NICE is expected to rule that the drug is just too expensive - and follow Scotland's example in denying patients treatment.

Tysabri is a monoclonal antibody that has also proven to be beneficial in treating Crohn's disease, which, like MS, is also an autoimmune disorder.

In MS, Tysabri was shown to reduce relapses by 67% against a placebo, and it slowed the progression of disability by 42%.

Medical experts admit it is impossible to compare results across different clinical trials.

But older-generation drugs, interferons and glatiramer acetate are generally acknowledged as demonstrating about a 30-35% decrease in relapse rate against a placebo.

And only two drugs have been shown to decrease the progression of disability - but again only by around 20-40%.

Source: Yahoo! Copyright © 2007 Yahoo! UK Limited. All rights reserved. (18/03/07)

The National Institute for Health and Clinical Excellence (NICE) issues guidance on the use of new and existing medicines, treatments and procedures within the NHS.

Tysabri is a new disease modifying drug for MS. Published trials show that in people with relapsing/remitting MS who are experiencing one or two relapses a year, Tysabri can reduce the relapse rate by 67%.

Safety concerns that came to light during clinical trials mean that, if recommended by NICE, Tysabri will only be available to people who have failed to respond to treatment with beta interferon or who have rapidly evolving severe relapsing/remitting MS.

The appraisal report is due to be published for public comment in the week commencing 2 April, although the final decision is not expected before July.

Chris Jones, Chief Executive of the MS Trust, comments “There is a well defined group of people with MS, where the disease is running out of control, for whom the risks of not treating far outweigh the potential risks represented by Tysabri. We sometimes forget that having MS is itself a huge risk and trust that NICE will recognise this when it makes its final decision."

Source: SpiritIndia.com (06/03/07)

Schmitt, 35, knows there is a slight chance the new drug might kill him, but without it his multiple sclerosis could flare up, bringing back the lack of feeling in his lower body, vision problems and difficulty walking.

"I didn't have much choice," he says.

Krista Chapman wakes up worried at 3 a.m. on the day of her first treatment.

After a horrible year of MS relapses in 2006, she reckons that the same drug, Tysabri, will reduce the odds of another setback from which she might not recover, sparing her from disorienting vertigo and overpowering fatigue.

But it also could cause a fatal viral infection in her brain. And at 37, she is too young to die, even though the odds of that seem slim.

As the drug, which costs several thousand dollars a month, slowly is infused into the back of her hand, she seems relaxed sitting up in her hospital bed.

For Schmitt and Chapman as well as an untold number of other MS patients, Tysabri has created a dilemma found with few other medications that treat disabling, but rarely fatal, diseases such as MS.

The drug was taken off the market in 2005 after three people out of about 2,900 who had been in clinical trials developed brain infections. Two of them died. There is no treatment for the infection, known as progressive multifocal leukoencephalopathy, or PML. And there is no way of knowing who will get it.

The risk of the complication initially was calculated to be about one in 1,000, but doctors say that is an estimate and no one knows the true risk.

In addition, because Tysabri works by blocking the ability of certain immune cells to get into the brain, it may make patients more susceptible to opportunistic infections in other parts of the body.

The drug was allowed back on the market in July with restrictions and a black box warning, the most serious alert that can be placed on a drug label.

The angst over the infection, in part, has been assuaged by Tysabri's huge promise. There is some indication that it may be twice as effective as other MS drugs and that it can reduce the number of relapses by two-thirds.

"If it wasn't for the (brain infection risk), everybody would be taking it because it is such a powerful drug," said Bhupendra Khatri, a neurologist and medical director of the Regional MS Center at Aurora St. Luke's Medical Center. "You need to be very selective about who you treat."

Beyond the grim calculus of risk and reward, MS patients may have to factor in another troubling variable: the staggering cost of Tysabri.

The drug has a wholesale price of $2,184 for each vial used for the standard, hour long monthly infusion session.

At least one infusion site, St. Luke's Medical Center, is billing nearly $10,000 for each monthly treatment.

Potentially, Tysabri patients could be on the drug for years, maybe the rest of their lives, possibly straining the lifetime policy limits of their insurance.

At the two other sites approved for dispensing Tysabri, the price is substantially less. Waukesha Memorial Hospital charges $2,900 for a monthly infusion. University of Wisconsin Hospital and Clinics in Madison bills $4,300. Under Medicaid, the state pays pharmacies about $2,400 for the drug.

All of those charges may be subject to rebates or discounts, depending on who is paying the bill.

For instance, a claim receipt from one Tysabri patient shows St. Luke's billed Humana Insurance $9,991, minus $3,996 for a plan discount, resulting in a net payment of $5,995. St. Luke's declined to comment on pricing.

A spokeswoman for the drug's maker said the company has no control over how much clinics charge for administering Tysabri.

Patient ranks growing
Despite the risk and the price, more patients are showing up each month at about 25 sites in southeastern Wisconsin that are approved to administer Tysabri.

Nationally, about 5,000 patients are taking the drug and another 3,000 are waiting to begin treatment, said Amy Brockelman, a spokeswoman for Biogen Idec, which markets Tysabri along with Elan Pharmaceuticals.

"We believe Tysabri has the potential to eclipse all the other MS therapies over time," she said.

MS is an autoimmune disease that usually is diagnosed in people between the ages of 20 and 50. About 400,000 Americans have the disease; women get the disease about twice as often as men. About 10,000 people in Wisconsin have MS.

In MS, certain immune cells enter the brain or spinal cord and mistakenly cause inflammation that damages myelin, the protective coating on the roots of brain cells. As the myelin becomes damaged, communication between brain cells is disrupted and some cells die, resulting in any of a variety of problems such as difficulty controlling movement, blurred vision and cognitive deficits.

Tysabri prevents the immune cells from getting into the brain. It binds to the surface of the cells and inhibits their movement from the bloodstream to the brain.

This helps prevent the autoimmune attack on the brain, but it also makes the brain more susceptible to a common pathogen known as the JC virus. It is the JC virus that causes the brain infection.

Closing the gate
Tysabri essentially turns the brain into a gated community, said John Fleming, a professor of neurology and director of UW's MS clinic.

"It keeps out all the criminals," Fleming said. "Unfortunately, it also keeps the cops out."

The problem in assessing the risk of Tysabri is that it has been tested for only about two years, he said. No one knows if the brain infection risk grows or diminishes five years out or longer, he said.

"If it turns out to be safe, it could be the predominant treatment for MS," Fleming said. "If there are more cases of (brain infection), it wouldn't surprise me if the FDA took it off the market."

For the moment, Tysabri patients such as Schmitt and Chapman may get some reassurance knowing that all three of the people who developed the brain infection had been on other immune-modulating drugs as well as Tysabri, and that may have contributed to their brain infections. Under the new restrictions that allowed Tysabri back on the market, it must be administered alone.

Schmitt, who was diagnosed with MS in 1998, has been part of a clinical trial to further establish the safety of Tysabri. He got his last infusion last month as part of the trial at St. Luke's. Since he went back on the drug last year, feeling has returned to the lower part of his body and he has never felt better, he said.

For Schmitt, a pharmacist who is married and has a 2-year-old child, his worries about the drug had to be set aside.

"I'm either disabled or still working," he said. "I'm 35. I've got to keep working."

Inspired by relapses
Chapman began considering Tysabri after she was hospitalised because of three separate relapses in 2006. During those setbacks, she had severe vertigo,  trouble speaking and swallowing, difficulty seeing and loss of feeling from the waist down.

She still has a great deal of fatigue and, at times, she gets around with a cane, walker or scooter.

"There are days when there is so much fatigue that I can't get out of bed," she said.

Chapman had been on a daily injectable MS drug, but it was losing its effectiveness, she said. She stopped another drug because it caused depression.

"All the neurologists said, 'You have to do something soon,' " she said. "It (going on Tysabri) was frightening. I knew the risk."

Her doctor, neurologist Stanya Smith, said for some patients the drug may be the only way to avoid disabling relapses.

"I have to be convinced in my heart as a physician that it's the only option I have left," said Smith, who manages the MS clinic at Waukesha Memorial.

For Chapman, the final decision was made over Thanksgiving weekend.

About 10 family members, including her husband, Jim, her parents and siblings, gathered at her mother-in-law's home in Oconomowoc. They each got a vote on whether she should go on Tysabri.

She got her first infusion at Waukesha Memorial last month.

Source: JS Online © 2007, Journal Sentinel Inc. All rights reserved. (04/03/07)

The Harry Potter author, whose mother had MS, broke her silence on the Scottish Medicines Consortium’s refusal to recommend Tysabri ahead of a debate on the drug by MSPs tomorrow.

Rowling said cost should not dictate the use of a drug which could help tackle a serious illness such as MS.

In December, the SMC said the economic case for Tysabri - which costs £15,000 a year per patient - had not been demonstrated.

The announcement prompted dismay among patients and MS campaigners.

The drug is used to treat patients who suffer an aggressive form of MS which leads to disabling relapses. The patients will have failed to respond to other treatments.

Yesterday, Rowling, patron of the MS Society Scotland, added her voice to the calls for the SMC to reconsider its position.

“I know from personal experience that MS can have a devastating effect on everyone who comes into contact with it. My mother suffered terribly with MS and it was so frustrating that there was little or nothing doctors could do to help her.

“If a drug can help tackle MS - particularly the very aggressive type of relapsing MS we are talking about - it should not be ruled out because of cost alone.

“Once again, decisions about treatment are being made by accountants rather than clinicians, and I hope MSPs will speak up on behalf of the thousands of families affected by MS across Scotland,” Rowling said.

Tomorrow MSPs will debate the motion “that the parliament deplores the decision by the Scottish Medicines Consortium not to recommend that Tysabri be prescribed to people with multiple sclerosis”.

Mark Hazelwood, director of the MS Society Scotland, said Tysabri was an important treatment option for MS patients.

“People affected by MS in Scotland should have the same access to treatments as their counterparts in Ireland, Germany, the US and elsewhere,” he said.

“More than 10,000 people are now taking this drug worldwide, but we are barely out of the starting blocks.”

Dr Belinda Weller, a neurologist at the Western General in Edinburgh, said she had been disappointed by the SMC’s decision not to recommend Tysabri.

It means doctors who want to use the drug for individual patients must apply to the health board for funding approval in each case.

Dr Weller said she had won approval to use Tysabri for one of her patients in Lothian, but doctors elsewhere in Scotland had been unsuccessful.

“There are gains to be made in improving quality of life in MS patients by using this drug which can help keep them in better health,” Dr Weller said. “It is important that we have the option to use it.”

SNP MSP Tricia Marwick, an MS campaigner, said she had been “astonished” by the SMC’s decision.

“Scotland has the highest incidence of MS in the world.

“If you have this level of illness you have the opportunity to become a centre of excellence in the treatment of MS,” she said.

“But with Tysabri we are lagging behind other countries.”

The Scottish Executive said the SMC was independent of ministers and, while it provided advice, doctors had to make judgments for each patient.

More than 10,000 people have the illness in Scotland - about one in 500 people.

But the reasons for the higher rate in Scotland remain unknown.

MS is the result of damage to myelin - a protective sheath surrounding the nerve fibres of the central nervous system. When this is damaged, it interferes with messages between the brain and other parts of the body.

Symptoms can include fatigue, mild to severe pain, balance and sight problems and muscle stiffness.

It is thought that about 1,000 patients in Scotland with aggressive MS could benefit from Tysabri.

Source: Alanat News (28/02/07)

Up until about six weeks ago, 48-year-old Darren Franchow was using a wheelchair.

The paralysing effects of M.S. had taken him down rapidly, following the diagnosis in December of 2005.

Darren Franchow, M.S. Patient: "It's devastating. I never felt so alone."

But that was then. This is NOW! IV steroids and an interferon treatment called REBIF worked for a while, but when they failed, Darren was given what is called the Tysabri therapy. Physicians have been trying it for a few years now. It doesn't work for all M.S. patients, but for some, like Darren, the drug infusion really pays off.

Darren Franchow: "A miracle. My wife and I have a very difficult time accepting this, almost as much as it was accepting I had M.S. What a blessing."

Shoveling snow? Who could have imagined this?

But even more significant, Darren, who heads up all the major computer interfacing for Salt Lake County Government, is able to continue working full time.

Darren Franchow: "If you can imagine thinking ‘I won't be able to do my job,' to the point now where I'm very excited because I'm seeing cognition coming back. I'm seeing the ability to put all the energy that I'm used to."

Darren still has his wheelchair, but it stays mostly in the back of his SUV. He now only uses it occasionally.

Source: ksl.com Copywrite KSL Television & Radio, Salt Lake City UT (20/02/07)

The Scottish Medicines Consortium (SMC) today (11/12/06) advised health professionals not to prescribe Tysabri (Natalizumab) - the only drug licensed for multiple sclerosis (MS) that has shown significant promise in slowing the progression of disability.

The Scottish Medicines Consortium (SMC) is  to announce its decision about whether or not Tysabri will be available with NHS funding for people with MS in Scotland on Monday 11 December at 2pm.

The decision for the rest of the UK will be taken by the National Institute of Health and Clinical Excellence (NICE) next year. It is expected that NICE will announce it's decision probably in July. (01/11/06)

US doctors are proving more wary than many had expected about prescribing Elan's multiple sclerosis drug Tysabri, which was relaunched in July after being suspended because of safety concerns.

Over the past month or so, analysts have drawn down their 2006 sales forecasts as it becomes clear that doctors wary of the risk of the rare but potentially fatal brain disease PML are reserving the drug as a treatment of last resort.

The drug, which is made by Elan and its US  partner Biogen Idec, had been expected by some analysts to generate sales this year of more than $100m, but those figures have dropped dramatically.

Ian Hunter, an analyst at Goodbody stockbrokers, said today that he has cut his full-year Tysabri forecast to $25.7m from $78m, partly because of continuing safety concerns and the complexity of reimbursement systems in Europe.

A survey of 63 US neurologists indicates that in 2006 Tysabri will be used in less than 1% of multiple sclerosis patients - translating into revenue of under $30m.

Since July, only 47 of more than 8,500 patients treated by US physicians surveyed had used Tysabri, even though more than 700 patients had discussed using it, according to the report. And more than 75% of the patients who had used Tysabri prior to its 2005 suspension have decided not to use it since its reintroduction, the survey showed.

In taking the rare decision to allow a withdrawn drug back onto the market, the US Food and Drug Administration was partially influenced by calls from patients who said they were willing to take the risk of contracting progressive multifocal leukoencephalopathy, or PML, because of the potential benefits of the drug.

Tysabri's ultimate sales potential will depend, to an acute degree, on whether there are any more cases of PML, analysts say. Most of the respondents to the survey said they would stop using Tysabri altogether if two new PML-related deaths were associated with Tysabri.

Source: RTE Business © RTÉ 2006 (23/10/06)

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