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    You are here : Home » MS Research News » Drugs » Lemtrada (alemtuzumab)

    Lemtrada (alemtuzumab)

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    Lemtrada (alemtuzumab) is a humanized monoclonal antibody being studied as a potential therapy for relapsing forms of multiple sclerosis. Alemtuzumab targets the cell-surface glycoprotein CD52, which is highly expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in MS, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte repopulation following alemtuzumab treatment.

    You can read about people's experiences on Campath within the What Has Helped You section of the website.

    Lymphocyte clue to multiple sclerosis drug, Alemtuzumab response

    T CellsPatients with rapid recovery of CD4-positive T cells after alemtuzumab treatment for multiple sclerosis (MS) are at risk for disease progression or relapse, research suggests.

    The difference was apparent from 3 months after treatment, implying the potential for individualized treatment protocols based on CD4+ counts, say lead researcher Neil Robertson (Cardiff University, UK) and colleagues.

    "The association between disease activity and early lymphocyte recovery is not surprising, as MS is primarily a cell-mediated disorder," they write in Neurology. "However, this relationship has not been demonstrated in vivo before."

    The researchers assessed 56 patients (40 women) given alemtuzumab 12 mg daily for 5 days to treat symptoms of MS. They observed an initial "profound depletion" of lymphocyte subsets, followed by gradual recovery.

    CD19+ cells were the first to recover, reaching the 25th percentile of average pretreatment levels at 3-6 months after treatment. These were followed by CD8+ cells, which reached a similar level after 6-9 months.

    Patients' average CD4+ cell counts remained below the 25th of pretreatment levels for up to 24 months of follow up (they received a second alemtuzumab course 12 months after initial treatment). However, recovery of CD4+ cells differed between patients who did and did not exhibit disease activity during follow up.

    In all, eight patients had a relapse, five had progressive disability, and four had asymptomatic lesions on magnetic resonance imaging. CD4+ cells were significantly higher at 6 and 24 months in patients with than without clinical relapse, and in those with than without new lesions.

    CD4+ counts diverged from 3 months between patients who remained stable and those with any clinical or imaging measure of new disease activity, remaining significantly higher in those with disease activity through 24 months.

    Having a 12-month CD4+ count above 400x106/mL was 81.1% sensitive and 73.7% specific for new disease activity by 24 months. "Current practice is to routinely image all patients at 24 months and to base treatment decisions on these scans and available clinical data," say Robertson et al.

    They note that the high negative predictive value of a low CD4+ count suggests that retreatment could potentially be restricted to patients with higher counts. "Inevitably this would be attractive in managed care programs and environments where access to imaging is difficult and this economic argument could be built on if larger studies support this assertion."

    Source: News-Medical.Net (19/12/12)

    Sanofi draws fire over cost of MS drug Lemtrada

    LemtradaMedical journal The Lancet warned that Sanofi's experimental multiple sclerosis drug Lemtrada may be too costly for patients and health insurers once it gets approved by regulators.

    The journal, which published the encouraging results of two late-stage Lemtrada tests on Thursday, also criticized the drugmaker's decision to withdraw leukemia therapy Campath, the same drug given at a different dosage, depriving MS patients who had been using it off-label.

    In an editorial accompanying the test results, The Lancet voiced concerns that Lemtrada would be priced higher than current MS drugs on the market and said the discontinuation of Campath may mean patients who had used it for MS would not be able to continue their treatment.

    The injectable drug, chemically known as alemtuzumab, was sold until September 2012 under the name Campath as treatment for leukemia and given more frequently at a higher dosage.

    "There is concern that with a license for multiple sclerosis, the cost of alemtuzumab could rise and might become too expensive for many patients and health systems," the editorial said.

    Although Campath remains available free of charge to leukemia patients, Sanofi's rare disease unit Genzyme pulled it off the market in September to prevent its unauthorized use as an MS drug.

    Analysts said the move would allow the company to adjust the price to match that of rival MS drugs on the market.

    A full course of Campath, which in 2011 had sales of $76 million, cost around $60,000 when given three times a week for up to 12 weeks, according to Genzyme.

    Lemtrada, instead, is given at less than half the dose of Campath for 5 consecutive days and then again for 3 days a year later. Since the drug has yet to be approved, it remains unclear how much Sanofi will charge for it.

    The drug, which works by resetting a person's immune system, has shown in late-stage trials to be an effective treatment for MS patients who have failed to respond to other therapies.

    It has also shown to benefit people not previously treated for the disease, suggesting it could be used as a first-line MS therapy.

    But patients need regular monitoring for serious side effects that can include infections and autoimmune diseases.

    "It's important that the appropriate safety monitoring is in place for patients who are prescribed Lemtrada," Genzyme's head of MS, Bill Sibold, told Reuters, responding to questions about the Lancet editorial. "Until an approved risk-management program is established, we believe the use of Lemtrada should only occur in clinical trials."

    Lemtrada remains available to patients who are taking part in clinical tests.

    Sibold declined to discuss pricing plans for Lemtrada, but said Genzyme has set up programs to make its approved drugs available to patients who cannot afford them. "With Lemtrada it would be no different," he said.

    DRUG FUNDING

    But there are concerns that cash-strapped European governments may balk at funding the drug through their public healthcare systems.

    Doug Brown, Head of Biomedical Research at U.K. charity MS Society said that while Lemtrada's results are great news for patients, the drug would only be useful to them if it were available through the country's publicly funded National Health Service.

    "We urge Genzyme to price the treatment responsibly so that if it's licensed, it's deemed cost effective on the NHS," he said.

    The U.K.'s cost-effectiveness body National Institute for Health and Clinical Excellence (NICE), whose opinions are also watched closely in other countries, initially rejected Novartis' MS pill Gilenya, only to make a U-turn after the company agreed to a discounted price.

    Sanofi launched its MS pill Aubagio in the U.S. at a price of $45,000 for a year's treatment, making it cheaper than rivals.

    Gilenya - the only other MS pill currently on the market - costs 28 percent more, while injectable treatments such as Biogen Idec Inc's Avonex and Teva Pharmaceutical Industries Ltd's Copaxone are 8 and 6.5 percent higher respectively.

    Source: Reuters © 2012 Thomson Reuters (01/11/12)

    Alemtuzumab lessens relapses, improves disability in MS - studies

    LemtradaTwo new trials offer proof that a leukemia drug long used to treat multiple sclerosis works better than a common treatment.

    When compared with the widely used drug interferon beta, the leukemia drug alemtuzumab reduced relapse rates by half, researchers say.

    Alemtuzumab Reverses Disability in Some

    Alemtuzumab has been used to treat MS for close to two decades, but it has never been approved for this use. It is given by IV infusion.

    The drug not only reduced relapses, but improved disability associated with MS, such as loss of coordination or difficulty walking, in some patients.

    Side effects include infusion reactions, infections, and potentially serious autoimmune disorders. Patients taking it must be followed closely.

    “In the menu of treatment choices for MS patients, I think alemtuzumab falls into the ‘high-reward, high-risk’ category,” says Alasdair Coles, MD, of Britain’s University of Cambridge, who led one of the newly published studies.

    “No other drug has been shown to offer the benefits in terms of disability improvement that this drug shows,” he says. "It comes with problems, but these problems are manageable.”

    400,000 MS Patients in U.S.

    The National MS Society estimates that about 400,000 people in the United States have been diagnosed with multiple sclerosis, and most (85%) have the relapsing-remitting form of the disease, in which symptoms come and go.

    These symptoms can include loss of feeling, coordination, and mobility, problems with thinking and vision, and depression.

    In one of the two newly published studies, University of Cambridge researchers followed 563 previously untreated patients treated with either alemtuzumab or interferon beta.

    Two years later, 22% of the alemtuzumab-treated patients had relapsed, compared to 40% of those treated with interferon beta.

    In the second study, which included 840 patients whose MS symptoms were not being controlled with other treatments, treatment with alemtuzumab was associated with 35% of patients relapsing over two years, compared to a 51% relapse rate among those treated with interferon beta.

    Patients in this study were also less likely to have additional MS-related disabilities after two years when they took alemtuzumab; 13% had disabilities compared to 20% of interferon-treated patients.

    1 in 3 Users Develop Autoimmune Disease

    In clinical practice, alemtuzumab has most often been used to treat patients who don't respond to other treatments or are no longer responding to them.

    Coles says he believes this is how the drug will continue to be used if it is approved as an MS drug in the U.K. and the U.S.

    He adds that about 1 in 3 patients who take the drug for MS develop an autoimmune disorder that affects the thyroid, and about 1 in 100 develop a disorder that involves blood platelets, which are involved in clotting and stopping bleeding.

    He says both conditions, while potentially serious, can be easily managed if patients are followed closely.

    “Close monitoring is critical because these side effects tend to appear a year or two after treatment, when MS symptoms are often under control and patients want to get on with their lives,” he says.

    National MS Society Chief Research Officer Tim Coetzee, PhD, says he does not see this as a big deterrent, since many of the newer drugs for multiple sclerosis also require close monitoring.

    “Given the choice between having a treatment that requires aggressive monitoring and not having that treatment at all, I believe that most patients will take the treatment any day of the week,” he says.

    Drug’s Cost as MS Treatment in Question

    The drug maker Genzyme plans to market alemtuzumab as an MS treatment in the U.S. and Europe, pending approval by government regulators. The drug will not be available to MS patients during the approval process.

    In an editorial published with the two studies, editors of the journal Lancet express concerns that the drug will be too expensive for patients and health systems when it is reintroduced as an MS treatment.

    “Finding promising treatments such as alemtuzumab is important,” they write. “But so is keeping alemtuzumab accessible and affordable if its early success in these trials proves to be of enduring value.”

    Source: WebMD ©2005-2012 WebMD, LLC (01/11/12)

    MS drug 'rebranded' to Lemtrada – at up to 20 times the price

    LemtradaPharmaceutical giant Sanofi withdraws existing treatment to boost profits with rebranded Lemtrada.

    A pharmaceutical company stands accused of putting profit before patients after withdrawing a drug used in the treatment of a chronic debilitating disease – ahead of relaunching it at a price predicted to be up to 20 times higher.

    Three of Britain's leading neurologists have written to the Health Secretary, Jeremy Hunt, to protest at Genzyme, part of the multinational drug company Sanofi, halting supplies of the drug alemtuzumab for multiple sclerosis.

    The drug is currently licensed for the treatment of leukaemia. But it has been known for 20 years also to be effective in MS patients suffering from an aggressive form of the disease.

    Neurologists have used the drug in these patients "off label" – prescribing it on their own initiative even though it was not licensed for multiple sclerosis – following encouraging results from a large placebo-controlled trial published in the New England Journal of Medicine in 1998. Alemtuzumab, which is given in two courses a year apart, costs markedly less than other drugs for multiple sclerosis to which it is thought to be superior – around £2,500.

    Genzyme has now applied for a licence for the drug in multiple sclerosis to regulators in Europe and the US and is expected to relaunch it under the trade name, Lemtrada, at what could be many times its current price. In the meantime the company has withdrawn the drug from MS patients' off-label treatment, pending the granting of the licence, on the grounds that "any adverse event outside a clinical trial … may complicate the regulatory process".

    In the neurologists' letter to the Health Secretary, professors Neil Scolding of the University of Bristol, Neil Robertson of the University Hospital of Wales and John Zajicek of the University of Plymouth say that Genzyme's decision has "serious implications for vulnerable UK patients with MS". They say patients who have already started treatment will "not be able to get their vital second course", and new patients may "miss their window of therapeutic opportunity" putting them at risk of "progressive, severe disability".

    When licensed, they say, the drug's price is expected to be "15 to 20 times greater", and its withdrawal sets an "inappropriate precedent". They add: "It shows little regard for patients whose opportunity to alter the course of their disease is time-limited, and may represent an over-enthusiastic attempt by the parent company to profit from the current situation."

    Professor Zajicek said he had personally treated about 150 patients with the drug, and 400 to 500 had received it across the UK. "Many of us think it is the best drug for patients with aggressive MS in the early stages of the disease. It's the greedy behaviour of the drug company that upsets me. They are just trying to rebrand it and put the price up. It is morally corrupt."

    A spokesperson for Genzyme said: "Our goal is to ensure that Lemtrada is approved by regulatory authorities and made available to multiple sclerosis patients as quickly as possible. Until approved risk-management programmes are established, the use of Lemtrada for MS should occur only in clinical trials. Off-label use of alemtuzumab in MS has always been at the discretion of individual clinicians without reference to the company."

    "In the UK, our price for Lemtrada and the value it brings to patients will be subject to the usual health economic evaluation by the National Institute for Health and Clinical Excellence."

    Doug Brown, Head of Biomedical Research at the Multiple Sclerosis Society, said: "Alemtuzumab shows real promise as a potentially new medicine for many people with relapsing-remitting MS. There is no good reason why people with MS who have been allowed to benefit from the treatment should now be denied it.

    "Genzyme need to come up with a scheme, quickly, that makes their product available to all those people currently being treated and, if it's licensed, price the drug reasonably so it is deemed cost effective on the NHS."

    A Department of Health spokesperson said: "We know how important this drug is for some MS sufferers and are working closely with the company and the NHS to help make sure these patients can still access it."

    Case study: 'I have seen the way my mother is suffering'

    Oritse Williams, 25, of the platinum-selling boyband JLS, knows the suffering caused by multiple sclerosis since his mother, Sonia, 54, was diagnosed over a decade ago. He and his brother pledged when in their teens that they would do all they could to help her.

    "We decided that when we grew up, my brother would become a scientist and I would try to make money from my music. That way we would have both the means and the ability to find a cure." Williams cared for his mother through his childhood and until he appeared in the final of The X Factor in 2008.

    The drugs company: Sanofi

    Sanofi, based in Paris, is the world's fourth-largest pharmaceutical company, employing 113,000 people worldwide.

    Last year the company made a profit of almost €6bn on revenue of €33b. Its products include Clomid, for female infertility, the anti-clotting agent Plavix and the cancer drug Taxotere.

    The company is the world's largest producer of vaccines through its subsidiary Sanofi Pasteur. It acquired Genzyme, a US biotech company based in Cambridge, Massachusetts, in 2011.

    In 2010 Sanofi sacked 1,700 US employees citing growing competition from non-branded generic manufacturers. It denied the action was related to its purchase of Genzyme.

    Last week, the Paris-based company announced plans to cut almost 1,000 jobs in France despite protests condemning the move.

    Source: The Independent © independent.co.uk (15/10/12)

    FDA refuses MS drug Lemtrada filing

    Oral MS DrugsGenzyme, a Sanofi company, announced it has received a Refuse to File letter from the U.S. Food and Drug Administration (FDA) in response to the supplemental Biologics License Application (sBLA) for the approval of Lemtrada™ (alemtuzumab) as a treatment for relapsing multiple sclerosis.

    After collaborative consultations with the FDA, the agency requested that the company modify the presentation of the data sets to enable the agency to better navigate the application. The FDA has not requested additional data or further studies. Genzyme will work with the FDA over the coming weeks to resubmit the application as soon as possible.

    “We have had constructive dialogue with the FDA, and we are very confident in our ability to address the agency’s request and resubmit rapidly,” said David Meeker, President and CEO, Genzyme.

    The company’s marketing authorization application submitted to the European Medicines Agency has been accepted and the review process is underway.

    Genzyme is developing Lemtrada in MS in collaboration with Bayer HealthCare.

    About Alemtuzumab/Lemtrada™

    Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.

    Genzyme holds the worldwide rights to alemtuzumab and has primary responsibility for its development and commercialisation in multiple sclerosis. Bayer HealthCare retains an option to co-promote alemtuzumab in multiple sclerosis. Bayer HealthCare has notified Genzyme of its intention to co-promote under this option. Upon regulatory approval and commercialization, Bayer would receive contingent payments based on sales revenue.

    *LemtradaTM is the proprietary name submitted to health authorities for the company’s investigational multiple sclerosis agent alemtuzumab.

    Source: Therapeutics Daily ©2011 UBM Canon (28/08/12)

    Campath pulled ahead of possible OK for Lemtrada for MS

    CampathSanofi's rare disease unit Genzyme is pulling leukaemia drug Campath to prepare for its launch under a different dosage and as a multiple sclerosis treatment that will be branded as Lemtrada.

    The withdrawal, meant to prevent the off-label use of Campath as a multiple sclerosis drug, is already under way in some European countries and will be effective in the United States on September 4, a Genzyme spokesman said.

    Lemtrada, which Sanofi submitted for approval with health regulators in Europe and the United States in June, could be launched in 2013 if it wins approval.

    If approved, it will be given far less frequently and in lower doses than Campath, and is one of the new products the French drugmaker is betting on to restore growth after losing several aging blockbusters to generic rivals.

    "We think that this stoppage shows Sanofi's confidence in the approval of Lemtrada in multiple sclerosis," said Bryan Garnier analyst Eric Le Berrigaud, who estimates the drug could generate sales of $400 million in 2018, if approved.

    The withdrawal will also enable Sanofi to adjust Lemtrada's price closer to that of rival multiple sclerosis drugs, Le Berrigaud said. Rivals include Tysabri, an injectable drug sold by Biogen Idec and Elan, while Novartis markets MS pill Gilenya.

    Campath, which last year had sales of $76 million, will continue to be available through patient access programs in the 50 countries where it has been available since its launch in 2001.

    "In most countries we will provide the drug for free, where this is permitted," the Genzyme spokesman said.

    The news was first reported by trade publication BioCentury.

    Source: Chicago Tribune © Chicago Tribune 2012 (22/08/12)

    Application submitted to FDA and EMA for approval of Lemtrada(TM) (alemtuzumab) for MS

    Oral MS DrugsGenzyme, a Sanofi company , today announced that the company has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) and a marketing authorization application (MAA) to the European Medicines Agency (EMA) seeking approval of Lemtrada(TM) (alemtuzumab) for treatment of relapsing multiple sclerosis (RMS). Genzyme is developing Lemtrada in MS in collaboration with Bayer HealthCare.

    Genzyme's clinical development program for Lemtrada included two Phase III studies in which results for Lemtrada were superior to Rebif(R) (high dose subcutaneous interferon beta-1a) on clinical and imaging endpoints, including a reduction in relapse rate. In addition, as presented last month at the American Academy of Neurology meeting, some patients with pre-existing disability treated with Lemtrada in the CARE-MS II trial were more than twice as likely to experience a sustained reduction in disability over two years than patients treated with Rebif.

    "There remains a large unmet treatment need for patients living with active disease and we believe that Lemtrada, given its efficacy and unique dosing schedule, has the potential to transform the lives of patients with MS," said Genzyme President and CEO, David Meeker.

    The regulatory submissions for Lemtrada include two-year controlled efficacy and safety data from both treatment-naive patients and those who relapsed while on therapy, with greater than five years of safety follow-up. Common adverse events associated with alemtuzumab were consistent across the Phase III program and included infusion-associated reactions and infections, which were generally mild to moderate in severity. Autoimmune adverse events were observed in some patients with cases being detected early through a monitoring program and managed using conventional therapies.

    In addition to Lemtrada, Genzyme's clinical development program for relapsing multiple sclerosis includes the once-daily oral treatment, Aubagio(TM) (teriflunomide), which is currently under review by the FDA and EMA.

    Source: MarketWatch Copyright © 2012 MarketWatch, Inc.(12/06/12)

    Lemtrada (alemtuzumab) improved disability scores in MS patients over Rebif

    LemtradaGenzyme, a Sanofi company , reports today additional data from the Phase III CARE-MS II trial. Accumulation of disability was significantly slowed in patients with multiple sclerosis (MS) who were treated with alemtuzumab versus Rebif(R) (high dose subcutaneous interferon beta-1a), as measured by the Expanded Disability Status Scale (EDSS), a standard assessment of physical disability progression.

    In addition, significant improvement in disability scores was observed in some patients treated with alemtuzumab from baseline and compared to patients treated with Rebif, suggesting a reversal of disability in these patients. In the trial, patients with pre-existing disability treated with alemtuzumab were more than twice as likely to experience a sustained reduction in disability than patients given Rebif. Genzyme is developing alemtuzumab in MS in collaboration with Bayer HealthCare.

    CARE-MS II was a randomized Phase III clinical trial comparing the investigational drug alemtuzumab to Rebif in patients with relapsing-remitting multiple sclerosis (RRMS) who had relapsed while on prior therapy. The company announced in November that results for the co-primary endpoints of the trial were highly statistically significant.

    Key disability data from the CARE-MS II trial presented today at the 64th Annual Meeting of the American Academy of Neurology include:

    -- The mean EDSS score for patients treated with alemtuzumab decreased over a two-year period, indicating an improvement in their physical disability, while the mean score for patients given Rebif increased, indicating a worsening of disability (-0.17 vs. 0.24; p < 0.0001).

    -- At two years, 29 percent of patients treated with alemtuzumab had experienced a six-month sustained reduction in disability, meaning their level of disability improved, as compared to only 13 percent with Rebif (p=0.0002).

    -- There was a 42 percent reduction in the risk of six-month sustained accumulation (worsening) of disability (SAD) as measured by EDSS in patients treated with alemtuzumab compared to Rebif over two years of study (p=0.0084), as previously reported. This was a highly statistically significant result for this co-primary endpoint.

    Key relapse data from the trial presented at AAN include:

    -- 65 percent of patients treated with alemtuzumab were relapse-free at two years, meaning they did not experience any relapses in the trial, compared to 47 percent with Rebif (47 percent risk reduction; p<0.0001).

    -- A 49 percent reduction in relapse rate was observed in patients treated with alemtuzumab 12 mg compared to Rebif over two years of study (p<0.0001), a highly significant result for this co-primary endpoint, as previously reported.

    "To date, a key goal for MS treatment has been to delay the worsening of disability," said Jeffrey Cohen, M.D., Director of Experimental Therapeutics, Cleveland Clinic Mellen Center for MS Treatment and Research; and a member of the Steering Committee overseeing the conduct of the study. "Patients in the study whose prior MS treatment was inadequate at preventing relapses and received alemtuzumab in the CARE-MS ll trial experienced a slowing or reversal of their disability."

    In the CARE-MS II trial, alemtuzumab 12 mg was given as an IV administration a total of eight times over the course of the two-year study. The first treatment course of alemtuzumab was administered on five consecutive days, and the second course was administered on three consecutive days 12 months later. Rebif 44 mcg was administered by subcutaneous injection three times per week, each week, throughout the two years of study.

    "Alemtuzumab is the first disease modifying therapy to show a significant effect both on relapse and disability endpoints over and above those of Rebif in a comparative trial," said Professor Alastair Compston, Chair of the Steering Committee overseeing the conduct of the study, principal investigator on the Phase II and III clinical trials of alemtuzumab, and Head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom. "The efficacy data from the CARE-MS trial program suggest that, if approved, alemtuzumab will be an important new treatment for relapsing MS patients with active disease."

    Additional new data from the CARE-MS II study suggest that alemtuzumab provided significant improvement over Rebif across a number of imaging endpoints, consistent with the effects observed in the clinical endpoints. In MS, imaging can be used to track the development of lesions, or patches of inflammation in the central nervous system (CNS). Statistically significant improvement was observed for alemtuzumab over Rebif in the percentage of patients with new or enlarging T2-hyperintense lesions (46 vs. 68; p<0.0001) and with gadolinium-enhancing lesions (19 vs. 34; p<0.0001). The change in T2-hyperintense lesion volume from baseline to year two, a secondary endpoint, was not significantly different (p=0.14). In the trial, patients treated with alemtuzumab experienced less change in brain parenchymal fraction (BPF), a measure of brain atrophy or loss of neurons and the connections between them, compared to Rebif (-0.62 vs. -0.81) median percent change from baseline (p=0.012), a significant result.

    "We believe these ground-breaking results from CARE-MS ll, including reversal of disability accumulation in some patients, achieved over the standard therapy Rebif, provide a message of hope for people living with MS," said David Meeker, M.D., President and CEO, Genzyme. "We are on track to submit alemtuzumab for review to U.S. and EU regulatory authorities in the second quarter of this year and are excited about the potential of bringing this important therapy to people living with MS who have unmet treatment needs."

    The most common adverse events associated with alemtuzumab in the CARE-MS Il study were infusion-associated reactions, which were generally mild to moderate. Infections were common in both groups, with a higher incidence in the alemtuzumab group. The most common infections included upper respiratory and urinary tract infections, cutaneous fungal infections and oral herpes. Serious infections occurred in 3.7 percent of the alemtuzumab group as compared to 1.5 percent of the Rebif group. Infections were predominantly mild to moderate in severity and none were fatal.

    In the trial, 15.9 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event compared to 5.0 percent with Rebif, and 0.9 percent of alemtuzumab-treated patients developed immune thrombocytopenia (ITP) during the two-year study period. These cases were detected early through a monitoring program and managed using conventional therapies. Patient monitoring for ITP and thyroid or renal disorders is incorporated in all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS. All data reported above pertain to patients in the trial who received alemtuzumab 12 mg or Rebif 44 mcg.

    Alemtuzumab is a monoclonal antibody that selectively targets CD52, a protein abundant on T and B cells. Treatment with alemtuzumab results in the depletion of circulating T and B cells thought to be responsible for the damaging inflammatory process in MS. Alemtuzumab has minimal impact on other immune cells. The acute anti-inflammatory effect of alemtuzumab is immediately followed by the onset of a distinctive pattern of T and B cell repopulation that continues over time, rebalancing the immune system in a way that potentially reduces MS disease activity.

    The company is on track to file for U.S. and EU approval of alemtuzumab in relapsing MS in the second quarter of 2012. Since it is not yet approved for the treatment of MS, alemtuzumab must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

    Source: MarketWatch Copyright © 2012 MarketWatch, Inc(25/04/12)

    Sanofi is looking at new compounds to expand MS business

    Oral MS DrugsSanofi, which bought Genzyme Corp. last year, is seeking new treatments to expand its multiple sclerosis business, said Michael Panzara, Genzyme’s therapeutic area head for multiple sclerosis, immune diseases and neurology.

    The drugmaker said today its experimental medicine Lemtrada, which it gained through Genzyme, led to an improvement in disability scores in patients suffering from multiple sclerosis compared with an older treatment in a late-stage trial. The company has another experimental MS therapy, Aubagio, which was under development before the Genzyme purchase.

    Beyond Lemtrada and Aubagio, Paris-based Sanofi has other experimental MS compounds in its pipeline “that we are actively starting to look at, and we’re always looking externally for good opportunities,” Panzara said in a phone interview today.

    Sanofi Chief Executive Officer Chris Viehbacher spent $20.1 billion last year to acquire Cambridge, Massachusetts-based Genzyme, the largest maker of medicines for rare genetic diseases. After the purchase, he folded Aubagio, Sanofi’s own MS therapy, into Genzyme to build up a multiple sclerosis business.

    Aubagio, whose chemical name is teriflunomide, is an oral therapy. Lemtrada, also known as alemtuzumab, is a so-called monoclonal antibody administered to patients through infusions for five consecutive days when they begin the treatment and for another three days 12 months later.

    “Alemtuzumab and teriflunomide we view as a beginning,” Panzara said. “You can’t have a world-class MS organization if you don’t fill up the pipeline at all stages of development.”

    Source: Bloomberg ©2012 BLOOMBERG L.P.(25/04/12)

    Alemtuzumab more effective than interferon β-1a at 5-year follow-up

    CampathSummary: The authors present 5-year follow-up data from the CAMMS223 study, reporting on the long-term safety and efficacy of alemtuzumab treatment compared with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72%. The annualised relapse rate over the 5 years was 0.11 for alemtuzumab and 0.35 for IFNβ-1a.

    Most commonly occurring serious side effects were serious infections occurring in 7% of alemtuzumab treated patients, with 30% developing thyroid problems (compared to only 4% in IFNβ-1a group).

    The study shows good evidence for the efficacy in reducing progression of disability and relapse rate reduction in patients with RRMS compared with IFNβ-1a and side effect profile in line with previously published data.

    Abstract
    OBJECTIVE:
    To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon β-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon β-1a (IFNβ-1a) through extended follow-up (up to 60 months from baseline).

    METHODS:
    Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNβ-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months.

    RESULTS:
    Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNβ-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNβ-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNβ-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNβ-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNβ-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFNβ-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab.

    CONCLUSIONS:
    Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNβ-1a, with a safety profile consistent with previous reports.Classification of Evidence:This study provides Class III evidence that alemtuzumab is more effective than interferon β-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period.

    Authors: Coles AJ, Fox E, Vladic A, Gazda SK, Brinar V, Selmaj KW, Skoromets A, Stolyarov I, Bass A, Sullivan H, Margolin DH, Lake SL, Moran S, Palmer J, Smith MS, Compston DA.

    Source: Neurology. 2012 Mar 21. and Pubmed PMID: 22442431 (28/03/12)

    Sanofi faces uphill struggle in MS drug market

    Lemtrada (Campath)Sanofi SA risks falling behind in the battle for share of the fast-growing multi-billion euro multiple sclerosis (MS) market, as rivals push ahead with revolutionary treatments while doubts remain over the French drugmaker's own drug candidates.

    Sanofi, which has relied on blood thinners and cancer therapies to drive sales but faces increased competition from generic drug versions, is preparing to submit two MS treatments for approval this year.

    But it faces an uphill battle to catch Novartis AG's Gilenya and Biogen Idec Inc's BG-12, set to dominate a market that JPMorgan analysts see growing to $14 billion (8 billion pound) in 2015 from $9.6 billion last year.

    "Sanofi will remain a small player compared with Biogen or Novartis, but it will still remain on the radar screen," said Beatrice Muzard, an analyst at brokerage Natixis.

    MS, which has no cure, affects 2.5 million people worldwide. It is a chronic, often disabling disease that attacks the central nervous system and can lead to numbness, paralysis and loss of vision.

    Standard treatment has involved injected drugs such as Teva Pharmaceutical Industries Ltd's Copaxone, Tysabri - sold by Biogen and Elan Ltd - and interferons. But the approval of Gilenya in 2010 introduced a potent new option in pill form.

    Gilenya and other oral MS treatments in late-stage development such as BG-12 are expected to drive growth in the sector.

    But analysts estimate Sanofi will grab only a modest share, given question marks over its drug candidates Aubagio and Lemtrada. Natixis' Muzard predicts the French firm's MS drugs could have peak sales of just 1 billion euros - not enough to plug the gap left by loss of earnings from the arrival of generic competition to its top blood thinner, Plavix.

    STICKING POINT

    Sanofi acquired Lemtrada through its $20.1 billion takeover of U.S. biotech group Genzyme last year, when it was already developing MS pill Aubagio. If approved, both drugs could end up reaching the U.S. and European markets by the end of the year.

    "It's pretty unusual for a company to come out with two new products at once, and actually cover the spectrum of the disease," Sanofi Chief Executive Chris Viehbacher told Reuters.

    Trouble is, there are doubts about both medicines.

    Lemtrada was the main sticking point in the protracted merger talks between Sanofi and Genzyme and, at the time, Viehbacher's team was keen to talk down its prospects. Genzyme had projected peak Lemtrada sales of $3.5 billion a year, while Sanofi pitched the number at around $700 million.

    The final deal between the two companies included a "contingent value right", a tradeable security that gives payouts to Genzyme investors if certain revenue targets are met, to bridge their differences.

    "When we were acquiring Genzyme, we were rightly sceptical of Lemtrada, because I am not keen on paying for things that are not proven," Viehbacher said.

    "Now that we have seen the clinical trial results - I have seen them but I cannot say more because we are going to publish them in April - we are very excited about this multiple sclerosis franchise."

    Unlike older MS drugs that have to be injected daily or weekly, Lemtrada is given just once a year.

    "I think Lemtrada is going to be completely different than everything else, which makes it difficult for the market to assess," said Viehbacher.

    Certainly analyst views vary widely. Morgan Stanley is forecasting 1 billion euros in peak sales for Lemtrada, while Nomura only sees $360 million.

    Medical experts back Viehbacher's view that a wider choice of treatments is needed given the unpredictable nature of MS.

    "Doctors and patients are looking for multiple options because the disease is so variable," said Tim Coetzee, chief research officer of the U.S.-based National Multiple Sclerosis Society. "A drug that is effective in some patients may not be effective in other patients."

    LATER STAGE

    Yet Lemtrada's prospects remain far from certain. During mid-stage tests the drug showed an unprecedented level of efficacy in reducing relapses over a three-year period, but this outcome was not repeated in a later-stage trial.

    It can also have serious side effects, which make it likely to be prescribed only to treat more severe forms of the disease.

    Compared with older therapies, Aubagio has the advantage of being an oral drug. But it has produced less impressive results in clinical tests than BG-12 and Gilenya - though heart issues have recently cast a shadow over Gilenya.

    In one recent study, Aubagio failed to show it was better than Rebif, a commonly used injectable interferon from Germany's Merck KGaA, although it did have milder side effects.

    "Aubagio won't take a lot of market share ... but it could find a niche on the basis of its safety profile," said Muzard, who is forecasting sales of around 400 million euros in 2018, compared with 2.6 billion for Gilenya.

    That niche could be found among newly diagnosed patients, since around 35 to 40 percent prefer to take no medication rather than face unwanted side effects.

    "Here's the challenge: convincing patients to start therapy," said Kevin Richard, co-founder of U.S. consultancy ClearView Healthcare Partners. "In this case Aubagio could be prescribed to patients who are not on interferons yet and who are hesitant to start injections."

    Sanofi filed Aubagio with the U.S. Food and Drug Administration in October and aims to submit it for approval in Europe in the first quarter of 2012, when it also expects to file Lemtrada with both regulators.

    Source: Reuters © 2012 Thomson Reuters (06/02/12)

    Successful phase III results for Alemtuzumab (Lemtrada(TM*)) in Multiple Sclerosis

    CampathGenzyme, a Sanofi company , reports today that the Phase lll CARE-MS ll trial met both of its co-primary endpoints.

    Relapse rate and sustained accumulation (worsening) of disability (SAD) were significantly reduced in multiple sclerosis patients receiving alemtuzumab (Lemtrada(TM)) as compared with Rebif(R) (44 mcg subcutaneous interferon beta-1a).

    Results for both of these co-primary endpoints were highly statistically significant. CARE-MS II is the randomized Phase III clinical trial comparing the investigational drug alemtuzumab to interferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS). Patients were required to have experienced a relapse while on a prior therapy to be eligible for CARE-MS II. Genzyme is developing alemtuzumab in MS in collaboration with Bayer HealthCare.

    In this randomized trial involving 840 patients, a 49 percent reduction in relapse rate was observed in patients treated with alemtuzumab 12 mg compared to interferon beta-1a over two years of study (p<0.0001). Importantly, there was also a 42 percent reduction in the risk of sustained accumulation (worsening) of disability as measured by the Expanded Disability Status Scale (EDSS) (p=0.0084). Analysis of the full CARE-MS II data is ongoing and results will be presented at a forthcoming scientific meeting.

    "CARE-MS ll represents the culmination of many years of clinical and laboratory research aimed at demonstrating the potential for alemtuzumab as a highly effective treatment for MS and understanding mechanisms involved in the complex natural history of the disease," said Professor Alastair Compston, Chair of the Steering Committee overseeing the conduct of the study and head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom. "Taken together, the Phase ll and lll clinical trial data illustrate the promise that alemtuzumab holds as a transformative treatment for people with relapsing MS."

    The CARE-MS II trial compared treatment with alemtuzumab 12 mg given daily as an IV administration for 5 days, and then again for 3 days one year later, to treatment with interferon beta-1a 44 mcg administered by injection three times per week throughout the two years of study.

    "The superior efficacy results for alemtuzumab, particularly the slowing of disability, are very promising since this was a head-to-head comparison trial with high dose subcutaneous interferon beta-1a," said Dr. Jeffrey Cohen, Professor of Medicine (Neurology), Cleveland Clinic Lerner College of Medicine; Director of Experimental Therapeutics, Mellen Center for MS Treatment and Research; and a member of the Steering Committee overseeing the conduct of the study. "These results suggest alemtuzumab's potential to offer patients with MS a new and effective treatment option."

    The safety profile observed in the trial was consistent with previous alemtuzumab use in MS and adverse events continued to be manageable. The most common types of adverse events associated with alemtuzumab in the CARE-MS II study were infusion-associated reactions, the symptoms of which most commonly included headache, rash, nausea, hives, fever, itching, insomnia, and fatigue. Infections were common in both groups with a higher incidence in the alemtuzumab group. The most common infections in patients receiving alemtuzumab included upper respiratory and urinary tract infections, sinusitis and herpes simplex infections. Infections were predominantly mild to moderate in severity and there were no treatment-related life-threatening or fatal infections.

    Approximately 16 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event and approximately one percent developed immune thrombocytopenia during the two-year study period. These cases were detected early through a monitoring program and managed using conventional therapies. Patient monitoring for immune cytopenias and thyroid or renal disorders is incorporated in all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

    "We are very pleased with the results of the CARE-MS II study which are unprecedented," said David Meeker, M.D., President and Chief Executive Officer, Genzyme. "We believe that Lemtrada(TM), with its impressive efficacy, novel dosing regimen and manageable safety profile, could make a very important contribution to the MS treatment landscape, where a significant unmet need still exists for many patients. Based on these positive results, we are on track to submit Lemtrada(TM) for review to US and EU regulatory authorities in the first quarter of 2012."

    Alemtuzumab has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA). The FDA's Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Under Fast Track designation, alemtuzumab for MS is eligible for Priority Review. Since it is not yet approved for the treatment of MS, alemtuzumab must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

    *Lemtrada(TM) is the proprietary name submitted to health authorities for the company's investigational multiple sclerosis agent alemtuzumab.

    About the CARE-MS II Trial

    CARE-MS II (The Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis) trial was designed to evaluate whether the investigational MS therapy alemtuzumab could achieve meaningful efficacy and safety improvements over the approved, active comparator interferon beta-1a, a standard treatment for relapsing MS.

    CARE-MS II was a Phase III, global, randomized clinical trial comparing treatment with alemtuzumab to treatment with subcutaneous interferon beta-1a (44 mcg administered by injection three times per week) in 840 patients who relapsed despite receiving prior MS treatment. Patients enrolled in the trial had to have experienced at least two relapses within the two years prior to entering the trial, with at least one of these relapses occurring within one year prior to enrollment and at least one relapse occurring while on MS therapy.

    The CARE-MS II trial had two co-primary endpoints: reduction in relapse rate and six months sustained accumulation of disability (SAD)**. Secondary outcome measures include: Percentage of relapse-free patients at year two; Expanded Disability Status Scale (EDSS) change from baseline; percent change in magnetic/resonance imaging (MRI)-T2-hyperintense lesion volume at year two; and Multiple Sclerosis Functional Composite (MSFC) change from baseline. Disability assessments were performed at regularly scheduled visits by independent, evaluating neurologists who were blinded to the patients' treatment assignments. Relapse was determined by a blinded committee.

    **Sustained Accumulation of Disability -- Clinical representation of the worsening of a patient's level of disability; CARE-MS ll monitored this endpoint over the course of six months.

    Source: Genzyme (14/11/11)

    Alemtuzumab offers hope for Multiple Sclerosis treatment

    CampathThe first drug to show signs of not just halting multiple sclerosis (MS), but actually reversing the nerve damage caused by the condition, has taken a significant step towards clinical approval.

    The results of a phase III trial, presented on 22 October at the 5th Joint Triennial Congress of the European and Americas Committees for Treatment and Research in Multiple Sclerosis, in Amsterdam, found that 78% of patients treated with the monoclonal antibody alemtuzumab remained free from relapse after two years -- and half the relapse rate of one of the standard therapies, interferon beta-1a (marketed as Rebif, among other names).

    However, alemtuzumab did not perform quite as well as it had in earlier trials. There was some evidence that it had reversed damage to nerves, but the result was not statistically significant, says Alasdair Coles, a neuroscientist at the University of Cambridge, UK, and the UK chief investigator of the Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) I trial.

    Coles told the meeting that magnetic resonance imaging showed that subjects taking alemtuzumab had also lost less brain volume than those taking Rebif, a proxy measure for overall tissue damage. "Alemtuzumab has eliminated the loss of brain tissue," he says.

    Just 8% of patients taking alemtuzumab experienced a worsening in disability according to standard measures, in comparison with 11% taking Rebif. There was no statistical difference between the two groups, but Coles puts this down to Rebif performing better than expected. "The patients recruited in this trial showed very little worsening of disability," he says.

    Significant promise?

    Ludwig Kappos, chair of neurology at the University Hospital of Basel in Switzerland, who has been involved in several MS drug trials, says he is disappointed that there was no significant effect on disability progression. "This is in contrast to what the phase II study has shown," he says. But he expects this effect to show up in another ongoing phase III trial: CARE-MS II, the preliminary results of which should be available later this year.

    There is no cure for MS, a condition caused by the body's own immune system attacking the myelin sheath that normally protects the nerves and speeds up neurological signals in the brain and spinal cord. At the moment, the only treatments are drugs such as interferon beta-1a and glatiramer acetate (Copaxone), both of which merely slow the progression of the disease.

    But alemtuzumab has the potential to reverse it: the drug tackles the mechanisms that cause damage to cells by effectively resetting the immune system. It targets the CD52 glycoproteins on the surface of mature immune cells, or lymphocytes, depleting levels of the aggressive T and B cells without affecting other lymphocytes. For reasons still not quite understood, when the lymphocytes repopulate, those involved in attacking the myelin sheath seem less likely to recover.

    Immune response

    Although the efficacy of alemtuzumab is impressive, performance was never really the issue, says Les Funtleyder, a health-care strategist at trading firm Miller Tabak + Co in New York. "With alemtuzumab the issue is safety," he says.

    The drug brings an increased risk of autoimmune diseases. In the trial, 18.1% of people taking alemtuzumab experienced thyroid-related autoimmune responses, and 0.8% developed the potentially life-threatening condition immune thrombocytopenia. But, says Coles, these findings mirror those from earlier trials, and it is possible to identify those patients most at risk by screening for certain biomarkers. "What's reassuring with this trial is that there are no new safety issues," he says.

    Some patients and clinicians who have already got wind of the alemtuzumab's efficacy seem unwilling to wait for clinical approval, says Coles. The drug is already approved in many countries as a treatment for some forms of leukemia and lymphoma, under the name Campath. In some countries, including the United Kingdom, it is legal to prescribe any drug for off-label use, and so patients have already started using it to treat MS, he says.

    But it is not just MS patients who have been holding their breath over this drug, says Funtleyder. Earlier this year, Genzyme, a drug company based in Cambridge, Massachusetts, that makes alemtuzumab and a range of other therapies, was acquired by Paris-based drug-maker Sanofi. The value of the deal for Genzyme's shareholders is contingent on the success of alemtuzumab in treating MS; the first milestone is for the drug to gain approval from the US Food and Drug Administration before the end of March 2014.

    This article is reproduced with permission from the magazine Nature. The article was first published on October 24, 2011.

    Source: Scientific American © 2011 Scientific American (25/10/11)

    Lemtrada (Campath) appears to help MS patients in study

    CampathNew data from a late-stage trial showed that 78 percent of patients treated with Lemtrada remained relapse-free for two years, compared with 59 percent using Rebif, an older multiple sclerosis drug sold by Germany's Merck.

    Lemtrada is a key experimental product at Sanofi's Genzyme unit. The fortunes of the drug are closely watched by holders of Genzyme Contingent Value Rights certificates issued to shareholders as part of the U.S. company's takeover deal.

    CVRs represent an extra fee holders will receive if Lemtrada hits certain targets or when Genzyme meets other milestones.

    The commercial potential of the drug, already sold under the brand name Campath as a leukemia treatment, was a key bone of contention between Sanofi and Genzyme during takeover talks.

    Multiple sclerosis, which affects 2.5 million people worldwide, is a chronic and progressive disease that attacks the central nervous system.

    Previously published data from the same late-stage study were mixed. Although Lemtrada was found more effective than Rebif at preventing relapses, it did not prevent the disease from becoming disabling, as it had in earlier trials.

    The results of the latest late-stage trial showed that side-effects, including respiratory and urinary tract infections, were mild to moderate, Sanofi said.

    Serious adverse events were similar between Lemtrada and Rebif, Sanofi said, with 18.4 percent of patients on Lemtrada suffering from side effects that included autoimmune disorders compared to 14.4 percent in patients taking Rebif.

    The drug's prospects should become clearer once the results of another late-stage trial are published by year-end. The study is comparing Lemtrada with Rebif in multiple sclerosis patients who have relapsed while on therapy.

    Sanofi plans to submit Lemtrada for U.S. and European Union marketing approval in the first quarter of 2012. The drug, if approved, will face competition from Novartis's Gilenya.

    Source: Reuters Copyright (c) Thomson Reuters 2011 (24/10/11)

    Autoimmune disease after alemtuzumab treatment for MS

    CampathSummary: Alemtuzumab is a monoclonal antibody, which is a candidate treatment for MS. One of the potential side effects of this medication was the development of autoimmune disease.

    In this study the authors prospectively analyse both clinical and serological data of patients with MS treated with alemtuzumab. It was found that autoimmune disease developed in 22.2% of those treated with a range of different systems affected, with thyroid autoimmune disease being seen most commonly (15.7%). It was found that sex and age did not have an influence on the frequency of disease; however smoking and a family history of autoimmune disease did increase its frequency.

    This study provides information on the development of autoimmune disease, which could be presented to patients being counseled prior to treatment with alemtuzumab.

    Abstract
    OBJECTIVE:
    To define the rate, timing, and clinical risk factors for the development of autoimmune disease (AID) after alemtuzumab treatment for multiple sclerosis (MS).

    METHODS:
    We analyzed prospective clinical and serologic data from 248 patients with MS treated with alemtuzumab, with median follow-up of 34.3 months (range 6.7-107.3).

    RESULTS:
    Novel AID developed in 22.2%. Thyroid AID was most frequent (15.7%). A range of hematologic, renal, and dermatologic AID were also observed as was asymptomatic development of novel autoantibodies. AID was seen from 2 weeks after initial treatment and was most frequent 12-18 months after first treatment. No new cases of AID were identified 60 months or more after initial treatment and risk of AID was independent of total alemtuzumab dose or interval of dosage. While established risk factors for AID including sex and age had no impact on AID frequency, both family history (odds ratio = 7.31, 95% confidence interval 3.02-17.68) of AID and a personal smoking history (odds ratio = 3.05, 95% confidence interval 1.50-6.19) were predictive of AID expression.

    CONCLUSIONS:
    Cumulative risk for AID in MS following alemtuzumab is 22.2%, most frequent between 12 and 18 months following first dose and evident for up to 5 years. Individual risk is modified by smoking and family history, which should be incorporated within the counseling process prior to treatment. Classification of evidence: This study provides Class IV evidence that the risk of AID after alemtuzumab treatment for MS is time-limited and modified by external factors.

    Authors: M. Cossburn, MD, MRCP, A.A. Pace, MD, J. Jones, PhD, R. Ali, MRCP, G. Ingram, MRCP, K. Baker, MRCP, C. Hirst, MD, J. Zajicek, PhD, N. Scolding, PhD, M. Boggild, MD, T. Pickersgill, MRCP, Y. Ben-Shlomo, PhD, A. Coles, PhD and N.P. Robertson, MD

    Sources: Neurology. 2011 Aug 9;77(6):573-9. and Pubmed PMID: 21795656 (14/09/11)

    Positive top-line results for first phase 3 study of Alemtuzumab (Lemtrada(TM)* in MS

    LemtradaSanofi and its subsidiary Genzyme announced today positive top-line results from CARE-MS I, the first of two randomized, Phase 3 clinical trials comparing the investigational drug alemtuzumab to the approved multiple sclerosis therapy Rebif(R) (high dose subcutaneous interferon beta-1a) in patients with relapsing-remitting multiple sclerosis (RRMS). Genzyme is developing alemtuzumab in MS in collaboration with Bayer HealthCare.

    In the CARE-MS I trial, 2 annual cycles of alemtuzumab treatment resulted in a 55 percent reduction in relapse rate compared to Rebif(R) over the two years of the study (p<0.0001), hence satisfying the first primary endpoint, and therefore meeting the predefined protocol criteria for declaring the study a success. Statistical significance was not achieved for the second primary endpoint, time to six month sustained accumulation of disability, as compared to Rebif(R). At the two year time point, 8 percent of alemtuzumab treated patients had a sustained increase in their Expanded Disability Status Scale (EDSS) score (or worsening) as compared to 11 percent of those who received Rebif(R) (Hazard Ratio=0.70, p=0.22). The patients will have the option to be evaluated over the next 3 years as part of a separate protocol.

    "The substantial effect of alemtuzumab on reduction of relapse rate over and above that seen with Rebif(R) confirms our experience gathered over many years and demonstrated in the Phase 2 study," said Professor Alastair Compston, Chair of the Steering Committee overseeing the conduct of the study, and head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom. "We treated patients in CARE-MS I at a very early stage in the course of their illness when the natural history may be relatively quiet, and both groups were remarkably stable over the two years of observation. Very few patients accumulated disability at the rate expected from previous clinical trials, including our Phase 2 experience. Whilst welcome from the clinical perspective, this much reduced our ability to detect a significant treatment effect on the disability endpoint."

    "In this 2-year comparative study, the effect of alemtuzumab on reducing relapses versus Rebif, a leading drug for the treatment of Multiple Sclerosis, is impressive, and the safety profile is consistent with the Phase 2 clinical trial experience," said Christopher A. Viehbacher, Chief Executive Officer, Sanofi. "We look forward to the results from CARE-MS II, which will provide clinical data in patients whose disease was not adequately controlled on other multiple sclerosis therapies. Today's results are an important step forward in the development of alemtuzumab to address the substantial unmet needs for multiple sclerosis patients."

    The most common adverse events associated with alemtuzumab in the CARE-MS I study included infusion-associated reactions, the symptoms of which most commonly included headache, rash, fever, nausea, flushing, hives and chills. The incidence of infections was also increased, the most common infections involving the upper respiratory and urinary tract and oral herpes. Infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections.

    No alemtuzumab patient discontinued from the study due to an adverse event. Less than 20 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event and less than 1 percent developed immune thrombocytopenia during the 2 year study period. There were no cases of anti-GBM disease. Cases of autoimmunity were detected and managed using conventional therapies. Patient monitoring for immune cytopenias and thyroid or renal disorders is incorporated in all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS. Analysis of the full CARE-MS I data is ongoing.

    CARE-MS I, which enrolled 581 early, active RRMS patients who had received no prior MS therapy, was a global, randomized, rater-blinded clinical trial to determine the efficacy and safety of alemtuzumab in this population. The company anticipates presenting detailed CARE-MS I study findings at a medical meeting later this year.

    Another Phase 3 clinical trial, CARE-MS II, is currently underway, evaluating alemtuzumab against Rebif(R) in relapsing-remitting multiple sclerosis patients who have relapsed while on therapy. Top-line results from that trial are expected to be available in the fourth quarter of 2011. Since it is not yet approved for the treatment of MS, alemtuzumab must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

    The company expects to file for U.S. and E.U. approval of alemtuzumab in MS in early 2012, and has been granted fast track designation by the FDA.

    *Lemtrada(TM) is the registered name submitted to health authorities for the investigational agent alemtuzumab.

    About the CARE-MS I Trial

    CARE-MS I (Comparison of Alemtuzumab and Rebif(R) Efficacy in Multiple Sclerosis, Study One) was a global, randomized, rater-blinded clinical trial comparing two annual cycles of intravenous alemtuzumab, 12 mg/day for 5 days initially and for 3 days a year later, to three-times weekly subcutaneous interferon beta-1a (Rebif(R)) in treatment-naive patients with RRMS. The study enrolled 581 patients who had not previously received treatment to suppress MS, except steroids. The study's primary outcome measures were reduction in relapse rate and time to sustained accumulation of disability. Secondary outcome measures include: Proportion of patients who are relapse-free at year two; Change from baseline in Expanded Disability Status Scale; Acquisition of disability as measured by change from baseline in Multiple Sclerosis Functional Composite; and Percent change from baseline in magnetic*/ resonance imaging (MRI)-T2 hyperintense lesion volume at year two. Additional endpoints included the safety and tolerability of alemtuzumab.

    About Alemtuzumab

    Alemtuzumab is a humanized monoclonal antibody being studied as a potential therapy for relapsing forms of multiple sclerosis. Alemtuzumab targets the cell-surface glycoprotein CD52, which is highly expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in MS, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte repopulation following alemtuzumab treatment.

    Source: Genzyme (11/07/11)

    Genzyme/Sanofi merger positions firms with two leading drugs in MS

    CampathGenzyme which plans to announce pivotal results from its program evaluating Campath in multiple sclerosis later this year, is also interested in broadening its portfolio in this indication, said Dr Michael Panzara.

    The company remains committed to researching the drug’s effect on the autoimmune system in light of certain side-effects seen in trials, said Panzara, who is group vice president of multiple sclerosis and immune diseases at Genzyme.

    Campath (alemtuzumab) is a chemotherapy drug that is currently used to treat B-cell chronic lymphocytic leukemia.

    Competition in the multiple sclerosis space is intensifying, as Novartis’ Gilenya, the first oral therapy was both approved and entered clinics last year. Competing drug, Biogen’s BG-12 recently reported a reduction in annualized relapses by 49% at two years, compared to the 23% reduction reported by Teva’s laquinimod in the same period. Biogen shares spiked more than 22% on the news, and if approved, it will be positioned as a new therapy alongside its current MS franchise, Tysabri and Avonex, which also reported increased sales.

    As multiple sclerosis treatment transitions towards a personalized approach and tailored therapy, Genzyme also has an active biomarker program in development to analyze predictors of safety for patients on the drug, noted Panzara. “Our company is currently evaluating when it is appropriate to switch patients. We’re constantly thinking about the most appropriate treatment algorithm,” he added.

    Panzara, who oversees Genzyme’s clinical development program for Campath, was previously chief medical officer of neurology at Biogen Idec, which manufactures Tysabri, a drug currently marketed for use in multiple sclerosis. Joining Genzyme approximately 18 months ago, Panzara said he has a mandate to build out Genzyme’s multiple sclerosis franchise. He was also the product leader for Tysabri and was heavily involved with the drug’s successful re-entry into the market after it was voluntarily withdrawn in 2005 due to concerns with brain inflammation. Tysabri was successfully re-launched into the market in 2006 with a risk management program.

    Campath will also need a risk management program for physicians to effectively manage the side effects with this compound, according to neurologists.

    Genzyme plans to submit data from three trials for FDA approval later this year. If reviewed favorably, Campath could be approved for the treatment of relapsing-remitting MS, the most common form of this neurodegenerative disorder, as early as next year, Panzara noted. The Phase III program will demonstrate the most appropriate place for Campath in MS, and determine how the drug will ultimately be used by physicians. The drug showed a very strong effect based on data from the Phase II trial in patients with active disease, he added.

    Genzyme expects to submit a complete package to the FDA that will include three studies: the Phase II trial, and the two Phase III trials: CARE-MS-1, CARE-MS-2. Results from the CARE-MS-1 trial are expected in 3Q11. CARE-MS-2 results are expected 4Q11. “From these studies, if the second study is also positive, Campath’s use may be for all patients across the MS spectrum,” Panzara said.

    Campath has received mixed reviews from the neurology community despite its efficacy, as it has been shown to cause idiopathic thrombocytopenic purpura (ITP), a blood disorder, in trials. The current label for Campath contains a label warning regarding the potential for developing serious blood complications with use.

    In the Phase II trials, 20% of Campath-treated patients developed thyroid disorders compared to 3% on Pfizer and Merck KgaA’s Rebif. However, data from a new study reported that Campath cut the risk of relapse in multiple sclerosis patients by 69% compared with Rebif after five years.

    Dr Samuel Hunter, a neurologist based in Tennessee who frequently prescribes Campath off-label in MS, said the drug will most likely be used as a second-line treatment. Hunter presented a study at the American Academy of Neurology (AAN) meeting highlighting Campath’s use as rescue immunotherapy for treatment-refractory MS patients.

    Aside from the Campath program, the company also has an active business development and research team in MS, said Panzara. The closest compound after Campath is a next-generation anti-CD52 compound which is in pre-clinical development. There are also small molecule compounds in development that target elements of inflammation, but the company could not discuss specifics.

    Merger yields pipeline synergies

    French-based pharmaceutical giant Sanofi-aventis closed its USD 20bn acquisition of Genzyme on April 8.

    The merger integration with Sanofi will not stop any in-licensing and external business development plans. “If it’s the right fit, the merger will not stand in the way. It’s business as usual at Genzyme,” Panzara said.

    The Sanofi merger also gives Genzyme access to its pipeline - in particular teriflunomide, an oral drug for relapsing-remitting multiple sclerosis that is currently in Phase III development. “We’re looking at how these drugs work together,” he said. The merger gives the companies combined resources, and unlocks a lot of synergy, he added.

    Top-line teriflunomide data was released in late 2010 with a 31% reduction in relapse rate and a 30% reduction in disability progression for the higher 14 mg dose.

    “There will be complementary synergies, and not a lot of redundancies,” he said.

    As for the current misunderstandings by the public and the divide within the neurology community regarding Campath’s safety profile and use, Panzara said that the company is limited in terms of how much medical education it can offer for Campath since it has not yet received approval in MS.

    However, he said, investigators who have used Campath have had the chance to better understand how the drug works, and “views change once there is better knowledge about what the Phase II data means”, he noted. “Neurologists will have to understand how to manage these side effects, similar to any drug.”

    Side effects have included ITP, thyroid disorders, and one case of anti-GBM, which affected the kidneys, said Panzara. The major side effects all fall under the category of autoimmune disorders, and the company is actively investigating the cause and mechanism of action behind these effects, he added.

    “We are looking at new animal models, evaluating autoimmune diseases and preventative therapies including blood-based biomarkers to help patients detect potential symptoms before they occur,” he said. “We are committed to minimize those risks.”

    There are currently more than 1,500 patients who have been treated with Campath in MS, Panzara said.

    Source: FT.com © Copyright The Financial Times Ltd 2011 (27/04/11)

    Alemtuzumab phase 2 data shows large percentage of MS patients remain Free of clinically-active disease

    CampathGenzyme Corp., a subsidiary of sanofi-aventis Group, today reported additional five-year patient data from its completed Phase 2 multiple sclerosis (MS) trial showing that nearly two-thirds of alemtuzumab treated patients remained free of clinically-active disease as much as four years after most patients received their last course of the investigational drug. The data were presented at the American Academy of Neurology's 63rd Annual Meeting.

    The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif® (high dose interferon beta-1a) in early, active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy. In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years. The study included an extended phase for collection of long-term efficacy and safety data.

    Results of the five-year review showed:

    An estimated 65 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 27 percent of patients taking Rebif (p<0.0001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without a sustained increase in disability as measured by the Expanded Disability Status Scale (EDSS) through five years;

    An estimated 72 percent of alemtuzumab-treated patients were relapse-free compared to 41 percent of patients taking Rebif; and
    an estimated 87 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 62 percent of patients taking Rebif (previously reported).

    "These data suggest that alemtuzumab may have great potential for MS patients," said abstract author Cary Twyman, MD, principal Investigator, Associates in Neurology, Lexington, KY.

    Two pivotal Phase 3 studies investigating alemtuzumab, CARE-MS I and II, are currently ongoing. Top-line results from these trials are expected to be available respectively early in the third quarter of 2011 and in the fourth quarter of 2011. The company expects to file for U.S. and E.U. approval in early 2012, and has been granted fast track status by the FDA for this submission.

    Alemtuzumab Seen to Improve Low-Contrast Vision

    Visual impairment is a common complication of multiple sclerosis. A second abstract presented at AAN reported that sustained improvement in visual contrast sensitivity, as measured by low-contrast letter testing, was more than twice as likely for those patients in the Phase 2 trial receiving the investigational drug alemtuzumab compared to patients receiving the active comparator Rebif.

    "Low-contrast letter acuity exams are a sensitive way of measuring visual function in MS clinical trials, and can correlate well with structural markers of the disease," said abstract author Laura Balcer, MD, Associate Professor of Neurology, University of Pennsylvania School of Medicine. "The improvements seen with alemtuzumab treatment as compared with interferon beta are encouraging."

    During the trial, patients were asked to identify letters on low-contrast letter charts, which capture the minimum size at which individuals can perceive letters of a particular contrast level (shade of gray on white background). Low-contrast sensitivity was measured for each eye at baseline and quarterly thereafter by masked raters.

    The analysis found that alemtuzumab patients were more than twice as likely to experience sustained improvement in vision as compared to Rebif patients (p=0.012). Alemtuzumab patients also realized a 46 percent reduction in the risk of sustained worsening in vision as compared to Rebif treated patients (p=0.0028).

    These data expand upon disability improvements as measured by the Expanded Disability Status Scale. The EDSS is a 10-point scale in which every 0.5-point step marks a notable deterioration in neurological capabilities. In the Phase 2 trial, as previously reported at month 36 and 60 the mean EDSS disability score of patients receiving alemtuzumab improved, while the mean disability worsened in the comparator group.

    About Alemtuzumab

    Alemtuzumab is a humanized monoclonal antibody being studied as a potential therapy for relapsing-remitting multiple sclerosis. Alemtuzumab targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in MS, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.

    About CAMMS223 Phase 2 Study

    In the Phase 2 trial, 334 patients with early active relapsing-remitting multiple sclerosis were randomized to treatment with alemtuzumab at one of two dose levels, or to the approved MS therapy Rebif® (high dose interferon beta-1a). Alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years. The majority of alemtuzumab treated patients last received the investigational drug at Month 12.

    The trial successfully met its two primary endpoints, reduction in relapse rate and reduction in the rate of sustained accumulation of disability.

    Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Sixty-eight percent of alemtuzumab patients participated in the follow-up program, and 60 percent were evaluated at 60 months. Forty-two percent of Rebif patients participated in the follow-up program, and 35 percent were evaluated at 60 months. Rater-blinded disability scores were assessed quarterly and relapses as-needed. A sensitivity analysis adjusted for patients receiving alternative disease-modifying therapy during the follow-up period, as well as for retreatment with alemtuzumab.

    Source: Genzyme © Business Wire 2011 (15/04/11)

    New data from Alemtuzumab phase 2 MS trial released

    CampathGenzyme, a subsidiary of sanofi-aventis Group announced today that it will present new data from its completed Phase 2 trial of the investigational drug alemtuzumab for multiple sclerosis (MS) at the American Academy of Neurology's (AAN) 63rd Annual Meeting in Hawaii, April 9 - 16, 2011.

    Included among the additional Phase 2 trial safety and efficacy data at AAN will be presentations on the clinically-active disease status of patients through five-years of patient follow-up as well as data describing a measure of vision improvement.

    "We are excited to present new alemtuzumab data at AAN that further reflects alemtuzumab's potential as an MS treatment," said Michael Panzara, Genzyme Group Vice President and Therapeutic Area Head for Multiple Sclerosis and Immune Diseases. "We look forward to the availability of Phase 3 results in the middle of this year."

    Alemtuzumab is a humanized monoclonal antibody being studied as a potential therapy for relapsing-remitting multiple sclerosis (RRMS). Genzyme is currently conducting two pivotal Phase 3 trials to evaluate alemtuzumab in the treatment of MS. CARE-MS I is a randomized trial comparing alemtuzumab to the approved MS therapy Rebif® (high dose interferon beta-1a) in early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other MS therapies. Data from these trials are expected to be available beginning in mid-2011.

    Genzyme's CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to Rebif in early, active, RRMS patients who had received no prior therapy. In the trial, which was larger and longer than most Phase 2 MS clinical trials, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years. The study included an extended phase for collection of long-term efficacy and safety data.

    Alemtuzumab data to be presented at AAN:

    Abstract titles

    - More Alemtuzumab Relapsing-Remitting Multiple Sclerosis Patients Are Free of Clinical Disease Activity at Five Years (Poster PD6.003, April 14)

    - Alemtuzumab Improves Contrast Sensitivity in Relapsing-Remitting Multiple Sclerosis Patients (Presentation S31.001, April 13)

    - Alemtuzumab Positively Affects Disability Outcomes Using a One-Year-Sustained Criterion for Relapsing-Remitting Multiple Sclerosis Patients in CAMMS223 (Poster P01.216, April 11)

    - Effect of Alemtuzumab vs. Interferon beta-1a on Brain Atrophy in Patients with Early, Active Relapsing-Remitting Multiple Sclerosis (Poster P05.042, April 13)

    About Alemtuzumab

    Alemtuzumab is a humanized monoclonal antibody being studied as a potential therapy for relapsing-remitting multiple sclerosis. Alemtuzumab targets the cell-surface glycoprotein CD52, which is often expressed on T- and B-lymphocytes. Preliminary research suggests that alemtuzumab depletes the T- and B-cells that may be responsible for the cellular damage in MS, while potentially sparing other cells of the immune system. Early alemtuzumab research has also suggested a distinctive pattern of lymphocyte reconstitution in patients following treatment.

    About CAMMS223 Phase 2 Study

    In the Phase 2 trial, 334 patients with early active relapsing-remitting multiple sclerosis were randomized to treatment with alemtuzumab at one of two dose levels, or to the approved MS therapy Rebif® (high dose interferon beta-1a). Alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years. The majority of alemtuzumab treated patients last received the investigational drug at Month 12.

    The trial successfully met its two primary endpoints, reduction in relapse rate and reduction in the rate of sustained accumulation of disability.

    Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Sixty-eight percent of alemtuzumab patients participated in the follow-up program, and 60 percent were evaluated at 60 months. Forty-two percent of Rebif patients participated in the follow-up program, and 35 percent were evaluated at 60 months. Rater-blinded disability scores were assessed quarterly and relapses as-needed. A sensitivity analysis adjusted for patients receiving alternative disease-modifying therapy during the follow-up period, as well as for retreatment with alemtuzumab.

    Source: Medical News Today MediLexicon International Ltd © 2004-2011 (09/04/11)

    Campath cuts MS relapse rates in patients at 5 years

    CampathCampath cut the risk of relapse in multiple sclerosis patients by 69 percent compared with Merck KGaA’s Rebif after five years, according to a study.

    Patients on Campath had an annualized relapse rate of 0.11, while for those getting Rebif the rate was 0.35 at the end of five years, according to data presented today at the European Committee for Treatment and Research in Multiple Sclerosis meeting in Sweden. Campath is currently used to treat a type of blood cancer.

    The study, from the second of three phases of clinical tests generally required for U.S. approval, is a five-year follow-up to data published in 2008 in the New England Journal of Medicine. Genzyme, based in Cambridge, Massachusetts, is now in the final stage of testing Campath, also known as alemtuzumab, for multiple sclerosis and expects data from those trials in 2011.

    “These long-term patient follow-up data suggest that alemtuzumab may have a significant disease-modifying effect in patients with early, active, relapsing-remitting multiple sclerosis,” said Alasdair Coles, a senior lecturer in the Department of Clinical Neurosciences at the University of Cambridge and a lead investigator of the trial, in a statement.

    Relapsing-remitting MS, the most common form of the chronic nerve disorder, is characterized by flare-ups of symptoms with some recovery in between relapses.

    Genzyme rose 8 cents to $72.68 at 9:41 a.m. New York time in Nasdaq Stock Market composite trading. Before today, the shares gained 48 percent this year, boosted by an unsolicited takeover bid for the company by French drugmaker Sanofi-Aventis SA.

    Once Yearly Dosing

    In the study, patients on Campath received a course of the medication once annually for two or three years. Campath is given by infusion in a cycle of about five days. Patients on Rebif were given the drug three times weekly for three years.

    The research found that 13 percent of patients taking Campath experienced an increase in disabilities compared with 38 percent of those taking Rebif, Genzyme said.

    Genzyme’s drug was associated with a 30 percent risk of developing an autoimmune thyroid problem, and six patients taking the drug developed a bleeding disorder called immune thrombocytopenic purpura, or ITP. The first ITP patient’s symptoms weren’t recognized and the disorder led to a fatal cerebral hemorrhage, the company said. One patient in the Rebif arm developed ITP.

    Safety, Side Effects

    “We’re not convinced that Campath is going to be a big product in multiple sclerosis,” said Phil Nadeau, an analyst with Cowen & Co., in a Sept. 30 telephone interview. “Efficacy looked great, but what will really determine how successful it is will be safety and side effects. In Phase 2 it had some issues.”

    Nadeau estimates that Campath could bring in about $500 million in annual revenue with added approval for multiple sclerosis. The drug had less than $150 million in 2009 revenue, according to Genzyme.

    Patients are monitored with blood and urine tests to detect such disorders, and most are remedied with treatment, said Michael Panzara, head of Genzyme’s multiple sclerosis and immune diseases unit.

    “What we’ve learned, in general, of potent treatments for MS is that you’re going to have a risk of various side effects,” Panzara said in a telephone interview yesterday. “The good news about our profile is we can detect these things.”

    2.5 Million People

    Multiple sclerosis, which affects about 2.5 million people worldwide including 400,000 in the U.S., is a disease in which the immune system attacks nerve coverings, damaging the brain’s ability to communicate with the rest of the body. The disease can cause blurred vision, loss of balance, slurred speech and tremors among other symptoms, according to the National Multiple Sclerosis Society.

    The first pill for the disease on the U.S. market, Gilenya from Novartis AG in Basel, Switzerland, was approved by the U.S. Food and Drug Administration in September. The medicine will compete with drugs given by injection, including Rebif from Darmstadt, Germany-based Merck KGaA, Avonex from Biogen Idec Inc. in Weston, Massachusetts, and Copaxone from Teva Pharmaceutical Industries Ltd. in Petah Tikva, Israel.

    Even compared with taking a pill every day, Genzyme’s Campath could be appealing to some patients who prefer to have treatment just once a year, said Nicholas LaRocca, vice president of healthcare delivery and policy research at the Multiple Sclerosis Society.

    “Compared to having to do any kind of daily dosing, whether it’s an injection or a capsule, the idea of only having to have a treatment once a year could be very convenient,” LaRocca said in an Oct. 1 telephone interview. “The more options that we can have available for people, the more likely it is that patients will find a therapy that works best for them.”

    Source: Bloomberg © 2010 BLOOMBERG L.P (15/10/10)

    Multiple Sclerosis treatment Campath granted fast track status by FDA

    CampathGenzyme Corporation announced that its alemtuzumab for multiple sclerosis development program has been granted Fast Track status by the U.S. Food and Drug Administration (FDA).

    This designation covers patients with relapsing-remitting forms of the disease.

    The FDA's Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Under Fast Track designation, alemtuzumab for MS is eligible for Priority Review and the FDA may consider for review portions of the marketing application before the submission of a New Drug Application (NDA) is completed.

    "We are extremely pleased that our alemtuzumab development program has been assigned Fast Track status, and look forward to working closely with the FDA to expedite the program's review process," said Henri Termeer, Genzyme's chairman and chief executive officer. "Alemtuzumab is a potentially transformative therapy for the treatment of multiple sclerosis, and an important part of our future."

    Alemtuzumab for the treatment of MS is currently being evaluated in two pivotal multi-center, multi-national trials, known as CARE-MS SM (Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis). The company's CARE-MS I Phase 3 trial is a randomized study comparing alemtuzumab to the approved therapy Rebif (high-dose interferon beta-1a) in early, relapsing-remitting multiple sclerosis (RRMS) patients who have received no prior therapy. The second Phase 3 trial, CARE-MS II, is comparing alemtuzumab to Rebif in RRMS patients who had active disease while on other MS therapies.

    Both trials are fully enrolled and data are expected to be available in 2011.

    About Campath® (alemtuzumab)
    Campath® is licensed in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the treatment of B-CLL in patients who have been treated with alkylating agents and for whom fludarabine combination therapy is not appropriate. The product was launched in its oncology indication in 2001 in the US, where it is marketed as Campath®, and in Europe, where it is named MabCampath®.

    Campath for B-CLL has a boxed warning that includes information on cytopenias, infusion reactions, and infections. The most commonly reported adverse reactions in patients with B-CLL were infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

    Source: World Pharma News © World Pharma News (15/06/10)

    Significant percentage of MS patients receiving Alemtuzumab in Genzyme's phase 2 trial remain free of clinically-active disease

    CampathGenzyme Corporation reported four-year follow-up data from its completed Phase 2 multiple sclerosis (MS) trial showing an estimated 71 percent of alemtuzumab treated patients remain free of clinically-active disease as much as three years after most patients received their last course of the investigational compound. The data were presented at the American Academy of Neurology annual meeting.

    The CAMMS223 Phase 2 trial, first reported in the New England Journal of Medicine in 2008, compared alemtuzumab to the approved MS therapy Rebif(R) (interferon beta-1a) in early, active, relapsing-remitting multiple sclerosis (RRMS) patients who had received no prior therapy. In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three times per week, every week for three years.

    Results of the four-year review found:

    -- an estimated 71 percent of alemtuzumab-treated patients were free of clinically-active disease, compared to 35 percent of patients taking Rebif (p<0.001). To be free of clinically-active disease, MS patients in the trial were both relapse-free and without progression of disability as measured by the Expanded Disability Status Scale (EDSS) throughout the course of the study;

    -- an estimated 91 percent of alemtuzumab-treated patients were free of sustained accumulation of disability compared to 68 percent of patients taking Rebif; and

    -- an estimated 77 percent of alemtuzumab-treated patients were relapse-free compared to 49 percent of patients taking Rebif.

    "These early data may set a new bar for clinical outcomes in multiple sclerosis," said Omar Khan, MD, Professor of Neurology, Wayne State University School of Medicine, site principal investigator in the CAMMS223 Phase 2 trial.

    Post-hoc analyses of the patients free from clinically-active disease were performed using data obtained from patients participating in CAMMS223. The dataset analyzed consists of the originally-planned three years of patient follow-up, additional continuous post-three-year follow-up, and prospective follow-up of patients who initially discontinued but returned to the study to participate in the risk management program. Roughly 15 percent of patients participating in the post-three-year follow-up used non-study MS disease modifying therapies. A sensitivity analysis that censored these patients found that the risk of relapse, sustained accumulation of disability, and free from clinically-active disease status favored alemtuzumab.

    Alemtuzumab Mechanism of Action Data

    Research suggests that in multiple sclerosis, T- and B-lymphocytes mistakenly attack the myelin sheath that protects nerve cells. These attacks can lead to disease progression and irreversible disability. The first detailed depiction of pharmacodynamic data from a large cohort of alemtuzumab treated relapsing-remitting MS patients (n=216) provided at AAN showed that alemtuzumab, in a selective fashion, targets T- and B-lymphocytes while largely sparing other immune system elements. The analysis also found that the targeted immune system cells begin to repopulate following treatment.

    "We believe that alemtuzumab targets the immune system cells responsible for the cellular damage found in multiple sclerosis, while sparing other immune system elements," said Alasdair Coles, MD, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge, a lead investigator of the Phase 2 clinical trial and author of the leukocyte dynamics abstract.

    Updated Safety Findings

    Immune thrombocytopenic purpura (ITP), an autoimmune disease, was identified in six alemtuzumab treated patients and one Rebif patient in the Phase 2 trial. Symptoms of ITP went unrecognized in the first alemtuzumab case and led to the onset of a fatal cerebral hemorrhage. Five other alemtuzumab-related cases were subsequently diagnosed and all five patients achieved durable remission, both with and without treatment during the Phase 2 study. New follow-up data presented at AAN show that these five patients continue to have normal platelet counts, and ITP has not been identified more than 16 months following the last alemtuzumab cycle. There have been no additional or recurrent events of ITP reported in the Phase 2 trial to-date.

    "In this study, alemtuzumab treated patients who experienced an ITP event and achieved remission have had no recurring episodes of ITP. The remissions were complete and durable," said abstract author Edward Fox, MD, PhD, Director of the Multiple Sclerosis Clinic of Central Texas, and a clinical site director for the Phase 2 and 3 trials.

    Additional new follow-up data presented at AAN show that the alemtuzumab-treated patients who experienced an autoimmune adverse event still experienced clinical benefits. Alemtuzumab patients with autoimmune adverse events had a 78 percent reduced rate of relapse, and 66 percent reduced risk for sustained accumulation of disability, compared to Rebif patients. Updated four-year data from the Phase 2 trial found that approximately 28 percent of alemtuzumab-treated patients developed an autoimmune thyroid-related adverse event. These events either normalized spontaneously or were managed using conventional therapies.

    Genzyme is conducting two Phase 3 pivotal trials to evaluate alemtuzumab in the treatment of MS. Both trials completed enrollment in 2009. CARE-MS I, a randomized trial comparing alemtuzumab to Rebif, is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other MS therapies. Patients who enrolled in those trials beginning in 2007 have completed the protocol-specified two years of follow-up and have begun to transfer into an extension trial. Data from the Phase 3 trials are expected to be available in 2011.

    About CAMMS223 Phase 2 Study

    In the Phase 2 trial, 334 patients with active RRMS were randomized to treatment with alemtuzumab at one of two dose levels, or Rebif. Patients were strongly encouraged to continue for two additional years of follow-up beyond the original three years of the study. Of the original sample, 158 patients completed a month 48 study visit (alemtuzumab n=122; interferon beta-1a: n=36). Alemtuzumab and Rebif were not provided by the study after the third year. Patients were allowed to continue Rebif or to receive other disease-modifying therapies during this follow-up period. The majority of patients last received alemtuzumab at Month 12.

    Common adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, particularly of the upper respiratory tract; infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections. Patient monitoring for thyroid disorders, ITP, and anti-GBM disease is incorporated into all Genzyme-sponsored trials of alemtuzumab for the investigational treatment of MS.

    Alemtuzumab is an investigational drug for the treatment of MS and must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

    Source: Genzyme Corporation (14/04/10)

    Follow-up data from Alemtuzumab phase 2 trial continues to show lasting benefits

    CampathGenzyme Corp. said that four-year follow-up data from its completed Phase 2 multiple sclerosis trial continued to show durable reductions in relapse rate and sustained accumulation of disability three years after the majority of patients received their last course of the investigational compound alemtuzumab.

    The accumulated four-year efficacy and safety data from the Phase 2 trial was presented at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting in Germany.

    The Phase 2 trial compared alemtuzumab to an approved multiple sclerosis therapy Rebif in early, relapsing-remitting multiple sclerosis or RRMS patients who had received no prior therapy. Three-year trial data were reported in the New England Journal of Medicine in last October.

    In the trial, alemtuzumab was given to patients in two or three annual cycles of not more than five days per cycle, while Rebif was given to patients three-times per week, every week for three years.

    The four-year analysis of early RRMS patients from the trial found that patients taking once-yearly cycles of alemtuzumab reduced their risk of relapse by 72% and the risk of sustained accumulation of disability by 73% compared to patients treated with the active comparator Rebif. These data closely mirror the three-year findings reported in the NEJM manuscript. Further, the annualized relapse rate and disability risk measured from year three to four remained at the same low level observed in prior years of the study.
     
    Genzyme also announced that its CARE-MS II Phase 3 trial, one of two pivotal trials of alemtuzumab in the treatment of multiple sclerosis, has completed enrollment. CARE-MS I Phase 3 trial, a randomized trial comparing alemtuzumab to Rebif, completed enrollment earlier this year. CARE-MS I is studying early, active RRMS patients who have received no prior therapy. CARE-MS II, which also compares alemtuzumab to Rebif, is studying RRMS patients who relapsed while on other multiple sclerosis therapies.

    Patients who enrolled at the start of both trials in 2007 will soon complete the protocol-specified two years of follow-up and begin to move into an extension trial which allows patients previously treated with Rebif to receive alemtuzumab. Patients previously treated with alemtuzumab will be allowed to take another treatment cycle as needed, said Genzyme.

    Source: RTT News © 2009 RTTNews. (12/09/09)

    Genzyme assumes primary responsibility for alemtuzumab in Multiple Sclerosis

    Campath

    Genzyme Corp. announced that it has completed the transaction with Bayer HealthCare to acquire the worldwide rights to Campath®/MabCampath® (alemtuzumab), giving Genzyme primary responsibility for the development and commercialisation of this promising multiple sclerosis (MS) therapeutic candidate. Genzyme is conducting two rapidly progressing phase 3 studies of alemtuzumab in relapsing-remitting MS patients.

    "Alemtuzumab for multiple sclerosis is a potential significant therapeutic advance for patients, and we are pleased to be leading this program that we expect will provide an important catalyst for the company’s long-term growth.”

    Under the terms of the transaction, Genzyme will make no upfront payment to Bayer. In exchange for the rights to alemtuzumab, Genzyme will make payments to Bayer following product approval under an earn-out arrangement that is based on product revenue. Similarly, in exchange for the rights to Campath, Genzyme will make future payments based upon revenue. 

    MS Development

    Genzyme is now leading the development program for alemtuzumab in MS, and following approval, will have primary responsibility for its commercialization.

    Alemtuzumab in MS is in two phase 3 trials. The first trial, for which enrollment is complete, treats early, active relapsing-remitting patients who have received no prior therapy. The second study, which is expected to complete enrollment before the end of this year, is studying relapsing-remitting patients who had active disease while on other MS therapies. Data from the trials are expected to be available in 2011, and approval is anticipated in 2012.

    Bayer, which has been co-developing alemtuzumab in MS with Genzyme, will continue to fund development at current levels until the investigational compound is approved for this indication.

    Source: Genzyme Corp. (02/06/09)

    Genzyme acquires worldwide rights to multiple sclerosis drug Campath

    Campath

    Genzyme Corp. has announced an agreement with Bayer HealthCare to acquire the worldwide rights of Campath, or alemtuzumab. The deal will give Genzyme primary responsibility for the development and commercialisation of Campath for the treatment of multiple sclerosis, or MS.

    Bayer will continue to fund a portion of the drug's development in MS and will retain an option to co-promote the product in MS upon approval. The deal is structured as an earn-out arrangement. Bayer will receive payments based on revenues and potential milestone payments if cumulative revenue targets are achieved. There are no upfront payments for the rights of these three drugs.

    In addition, Genzyme will assume sole responsibility for the worldwide sales and marketing of Campath in B-cell chronic lymphocytic leukemia, or CLL. Meanwhile, Bayer will retain the right to develop and commercialise alemtuzumab in solid organ transplant indications.

    Genzyme said the transaction is accretive and has already reflected in the company's 2009 revenue and non-GAAP earnings per share guidance. The deal also supports the company's goal of 20% compound average non-GAAP earnings growth from 2006 to 2011.

    Source: RTT News © 2009 RTTNews(01/04/09)

    Buzz around Campath proof-of-concept trial in MS

    Campath

    When news broke in October that an approved cancer therapy had, for the first time, halted the progress of multiple sclerosis (MS), excitement was tangible among clinicians and patient groups. The phase 2 study's results are certainly unprecedented in MS. But whether Campath (alemtuzumab), a monoclonal antibody (mAb) already approved to treat leukemia, actually 'reverses' MS, as some news stories in the mainstream media trumpeted, and how it works remain unresolved. The next two years are expected to reveal much about not only Campath in MS, but also the competitive landscape for this indication where the tradeoff between efficacy and safety remains a tough hurdle for drug developers.

    Campath was the first humanized mAb to be developed as a therapy. It has a long, illustrious history, dating back over two decades to anti-lymphocyte rat antibodies first raised by Herman Waldman and Geoffrey Hale (Mol. Biol. Med. 3, 305–319, 1983). The name Campath derives from the pathology department at Cambridge University, UK, where the academics worked.

    The monoclonal was raised to target B and T cells and was initially pursued as treatment for graft-versus-host disease. However, Campath took off as a therapeutic only when Greg Winter and colleagues, also at Cambridge University, humanized the recombinant DNA-derived antibody, which became known as alemtuzumab.

    Campath targets the cell surface glycoprotein CD52 present on all mature lymphocytes and has been used to treat B-cell chronic lymphocytic leukemia since 2001 when it was approved. The notion that Campath might also work as a treatment for MS was pioneered in 1991 by Alistair Compston, at Cambridge University, UK, also the lead investigator in the recent New England Journal of Medicine study (N. Engl. J. Med. 359, 1786, 2008). He speculated that the antibody might work by destroying the mature T and B lymphocytes that drive the autoimmune attack against nerves and brain tissue in MS patients. After treatment, the immune system would be replenished, but this time, without the auto-reactive lymphocytes.

    The strategy is indeed promising. Results from the latest study, funded by Cambridge, Massachusetts–based Genzyme and partner Bayer Schering, of Leverkusen, Germany, look "extremely attractive," says Jerry Wolinsky, who directs the Multiple Sclerosis Research Group at the University of Texas Health Science Center in Houston.

    In the phase 2 trial, known as CAMMS223, Campath was administered once yearly to 334 previously untreated individuals with early relapsing-remitting MS. This regime cut patients' risk of relapse by 74% and reduced the rate of sustained accumulation of disability by 71%, compared with patients treated with the standard treatment Rebif, a high-dose interferon -1a from Merck Serono. Patients were followed for three years; those on Campath scored higher on a standard disability scale than before starting the treatment, whereas patients on Rebif deteriorated. The benefits were long lived, lasting at least three years.

    Even more striking, perhaps, are the magnetic resonance imaging scans that suggest the drug may be reversing the symptoms of the disease. Imaging data revealed that people in the Campath arm increased brain volume after a year, whereas the brain volume in the group receiving standard interferon experienced a decline.

    "We're not saying people are cured," cautions neurologist David Margolin, Genzyme's lead medical monitor in the phase 2 and ongoing phase 3 program. But Campath patients' disability scores improved dramatically "within a few months, and this is not driven by just a few individuals," adds Margolin, who has an MS specialty practice at Massachusetts General Hospital and the Brigham and Women's Hospital in Boston. "Clearly, there is some recovery occurring, only in the [Campath] population as a group. Thirty percent of Rebif patients improved, but more of them worsened," whereas Campath achieved "remarkable stabilization" of disease. The other benefit of Campath is its once-yearly administration.

    "It's not reversing MS," says Lauren Krupp, neurologist at Stony Brook University Hospital in New York and director of the Pediatric Multiple Sclerosis Comprehensive Care Center, who is nonetheless guardedly optimistic. "You have patients with relapses and remissions. If you get rid of the relapses, then over time, it's going to look like there is less [of a] persistent neurologic deficit. It's just a function of the drug's effects on the relapses, rather than turning the disease around."

    The claims of disease reversal regarding Campath are still "a big stretch," says Wolinksy, who points out that the extrapolations are made by hopeful onlookers and boosters and not by the drug makers Genzyme and Bayer Schering. "The absolute good news is, if we treat early and aggressively, we can expect remarkable outcomes, but at a cost for a fair percentage of patients."

    Clinicians and regulators worry over side effects, particularly the risk of developing a rare neurological condition progressive multifocal leukoencephalopathy (PML), the brain infection that bedevils the -4 integrin antagonist Tysabri (natalizumab), co-marketed by Biogen Idec, of Cambridge, Massachusetts, and Dublin-based Elan. Thus far, no cases of PML have shown up in MS patients exposed to Campath. Years of experience using Campath for chronic lymphocytic leukemia treatment may not be informative as patients with this form of leukemia can develop PML, independently of Campath.

    Despite the troubles associated with Tysabri, people with MS may still retain "an overall positive view" toward the treatment, says David Williams, head of business development for PatientsLikeMe, an online health community for patients with life-changing conditions including MS. "Campath will be the same way, if it's approved," Williams predicts, though the risks as known so far are hardly identical.

    With Campath, safety issues could arise over a potentially fatal autoimmune disorder. In the phase 2 trials, 20% of Campath-treated patients developed thyroid disorders compared to 3% on Rebif. Krupp notes, however, that thyroid trouble seems to occur with MS anyway, for reasons that are not well understood. More serious is the development of immune thrombocytopenic purpura (ITP). Three patients in the Campath group developed this complication and one of them died. "Some people would suggest management of ITP is easy, but if it were straightforward and easy, they wouldn't have had the first one die," Wolinsky says. Margolin notes that the fatal case of ITP—the first to arise —"took everyone by surprise," whereas the others fully recovered with treatment, and one did so spontaneously. Krupp, for her patients, "would consider [Campath] in patients where all of those things, as bad as they sound, are 'not as bad' as what's happening with their MS."

    Other promising mAbs in late-stage development for MS include Rituxan (rituximab), an approved therapy for rheumatoid arthritis and non-Hodgkin's lymphoma from Biogen and S. San Francisco, California–based Genentech, in phase 3 trials. Another drug currently in phase 2 studies is Zenapax (daclizumab), an immunosuppressant mAb for organ transplants from Biogen and PDL Biopharma of Fremont, California. Leerink Swann analyst William Tanner wrote in a September research report that consultants were "not overly impressed" with Zenapax, holding out hopes for other compounds, though the safety profile of Campath may be of concern. Still in the game, but just barely, is Basel–based Novartis' S1P1 modulator FTY720 (fingolimod), which has run into serious safety issues in pivotal testing.

    For Campath, efficacy could win over safety concerns. One phase 3 trial aims to enroll 525 patients like those in phase 2 with early, relapsing, remitting disease; the other will test relapsing MS patients and intends to enroll 1,200. Campath could be filed for approval with the FDA as early as 2011, probably as a monotherapy. "With the findings to date, I don't see any reason to add another drug," Margolin says, though some neurologists speculate that Campath might be used as induction therapy, to be followed by interferon or Copaxone (glatiramer).

    An ongoing debate in MS therapy is how the disease's inflammatory and neurodegenerative aspects overlap and what this means for drug developers. "None of these drugs are going to fix neurons that are dead and gone, but some probably will help to slow the neurodegenerative processes," Margolin says. "We hope our trials will establish Campath as the treatment of choice, if patients are relapsing."

    Source: nature biotechnology © 2009 Nature Publishing Group (16/01/09)

    Campath may benefit Multiple Sclerosis patients

    Campath

    Multiple Sclerosis patients have significant and sustained reduction in disability and risk of relapse on Alemtuzumab versus Rebif(R).

    Genzyme Corporation and Bayer HealthCare Pharmaceuticals Inc. today announced study results showing that patients with early relapsing-remitting multiple sclerosis (RRMS) taking once-yearly cycles of alemtuzumab reduced their risk of relapse by 74 percent and the risk of sustained accumulation of disability by 71 percent compared to patients treated with the active comparator Rebif® (high-dose interferon beta-1a).

    Importantly, the mean disability of patients on alemtuzumab improved from baseline, whereas the mean disability of those on Rebif worsened. The treatment benefits of alemtuzumab were sustained for at least three years, even though the majority of alemtuzumab-treated patients were last dosed two years earlier. These results come from the final three-year analysis of a Phase 2 clinical study (CAMMS223) reported in the Oct. 23 issue of the New England Journal of Medicine. The study involved 334 patients who had not previously been treated for their disease.

    “The alemtuzumab trial data continue to suggest a potentially new and exciting treatment for patients with early, active multiple sclerosis,” says Alastair Compston, Professor of Neurology and the head of the Department of Clinical Neurosciences at the University of Cambridge, United Kingdom, and the study’s principal investigator. “This randomized study confirms findings from prior studies demonstrating that treatment with alemtuzumab can have a profound and durable impact on patients with relapsing-remitting multiple sclerosis, including restoring some lost function in many patients.”

    Symptoms of multiple sclerosis result from an immune system attack on the protective insulation surrounding nerve fibers of the central nervous system. We believe alemtuzumab shuts down this immune system attack, treating the disease at its root cause,” says Alasdair Coles, Senior Lecturer, Department of Clinical Neurosciences, University of Cambridge and a lead investigator in the study.

    Common non-serious adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, which were predominantly mild to moderate in severity, as well as autoimmune thyroid disease. Three percent of alemtuzumab-treated patients developed the potentially serious autoimmune adverse event immune thrombocytopenic purpura (ITP), a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. Additional study and trial safety information is below.

    “The trial was larger and follow-up was longer than the typical Phase 2 trial in multiple sclerosis. It is important to note that we compared the investigative drug directly against a widely used therapy rather than against placebo. The trial did not show an increased risk of life-threatening or opportunistic infections, but a proportion of alemtuzumab patients experienced new autoimmune disease. We have been able to create a robust patient monitoring program that allows us to proceed into our two international Phase 3 trials with greater assurance on safety associated with patient management,” says Dr. Richard Moscicki, chief medical officer for Genzyme.

    According to the National Multiple Sclerosis Society, approximately 400,000 Americans acknowledge having MS, and every week about 200 people are diagnosed. Worldwide, multiple sclerosis may affect 2.5 million individuals. The disease causes a wide range of symptoms including difficulty with walking, numbness, fatigue and impairment of vision, and progresses to permanent, severe disability in the majority of patients. Relapsing-remitting MS is the most common presenting form of the disease.

    “We are pleased to see potential new treatment options move positively through the MS pipeline,” says Dr. John Richert, executive vice president for research and clinical programs at the National Multiple Sclerosis Society, “and as alemtuzumab is moved into Phase 3 studies, we hope that individuals with MS will consult with their physicians to assess whether they are appropriate patients and if so will consider the pros and cons of participating in these important clinical trials.”

    Helen Yates of the MSRC said: "The work that Professor Alastair Compston and his team have been doing with Alemtuzumab has looked interesting for some time.  This latest news is very exciting indeed and has huge significance in the treatment of relapsing remitting MS. 

    Although there are some significant potential side effects the clinicians seem to have learned to control or treat these and the potential benefits do seem to outweigh the risks."

    Additional New Top-Line Data

    New and previously unreported top-line data from secondary analyses of the CAMMS223 Phase 2 clinical trial, presented last month at the World Congress on Treatment and Research in Multiple Sclerosis (WCTRIMS), revealed that the proportion of clinically disease-free patients was significantly higher in the alemtuzumab group than in the Rebif group at year one (86 percent vs. 63 percent), year two (81 percent vs. 48 percent), and year three (71 percent vs. 39 percent, p-values <0.0001). “Clinically disease-free” was defined as the absence of both relapses and sustained accumulation of disability during the time-period assessed.

    The top-line data from WCTRIMS also showed that the proportion of patients free of sustained accumulation of disability over a six-month period was also significantly greater in the alemtuzumab group than in the Rebif group at year one (97.2 percent vs. 87.0 percent), year two (94.3 percent vs. 82.4 percent), and year three (91.0 percent vs. 73.8 percent, p-values <0.005).

    Further, the proportion of relapse-free patients over time was significantly greater in the alemtuzumab group than in the Rebif group at year one (91.1 percent vs. 69.3 percent), year two (88.2 percent vs. 58.5), and year three (80.2 percent vs. 51.6 percent, p-values <0.0001).

    Phase 2 Extension Trial

    Genzyme with Bayer support has launched an extension of the CAMMS223 trial to examine safety and efficacy outcomes beyond three years, and to compare two distinct retreatment strategies. The results should provide an understanding of the long-term effects of prior alemtuzumab treatment as well as the safety and sustained efficacy of additional alemtuzumab retreatment delivered in fixed annual cycles or as needed for resumed MS disease activity. In the fixed arm, patients will receive two annual cycles of alemtuzumab (12 mg/day for three consecutive days/cycle). In the as-needed arm, retreatment is deferred until a patient relapses or develops two or more new/active brain lesions on MRI.

    Phase 3 Trials

    Genzyme with Bayer support is sponsoring two Phase 3 trials in which patients are now enrolling. The CARE-MS I Phase 3 study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), is a randomized, rater-blinded study that will again compare alemtuzumab to Rebif in patients with relapsing-remitting MS who have not been previously treated for their disease. The CARE-MS II trial is studying patients who have continued to relapse while using approved MS therapies.

    About Study CAMMS223

    In the Phase 2 trial, 334 patients with active relapsing-remitting multiple sclerosis were enrolled at 49 medical centers in Europe and the United States. Patients in the trial were randomized to treatment with alemtuzumab at one of two dose levels (12 or 24 mg per day intravenously) for five days during the first cycle and three days 12 months later during the second cycle of therapy, or Rebif (44 mcg administered by subcutaneous injection three times per week, as indicated in its product label). A third cycle of alemtuzumab therapy was received by 46 patients at month 24.

    The trial compared the efficacy of alemtuzumab with Rebif using two primary outcome measures: the Relapse Rate and the time to Sustained Accumulation of Disability as evidenced by an increase in the Expanded Disability Status Scale (EDSS) score for six consecutive months. Efficacy assessments were made by independent neurologists blinded to patients’ treatment assignments. The EDSS is a 10-point scale in which every 0.5-point step marks a notable deterioration in neurological capabilities.

    The mean disability score of patients after alemtuzumab actually improved (by 0.39 EDSS points) indicating a recovery of neurologic functions. The median disability score improved to a similar extent after alemtuzumab. In contrast, mean disability worsened in the Rebif group (by 0.38 EDSS points) resulting in a difference of nearly a full EDSS point (0.77 difference, p<0.0001) at three years.

    Safety Data

    A total of six alemtuzumab-treated patients, and one Rebif-treated patient, in this study developed a serious adverse event, immune thrombocytopenic purpura (ITP). ITP is a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. The Rebif patient with ITP was asymptomatic but ITP persisted at the time of study completion. In the previously reported alemtuzumab-related fatal case, symptoms of ITP were experienced but were not recognized in time, thus delaying medical attention. Of the remaining alemtuzumab cases, four patients were diagnosed promptly, responded well to medical treatment, and have been stable without a need for ongoing treatment. The other alemtuzumab-treated case experienced spontaneous remission of ITP. A patient monitoring program was instituted in the trial, and there have been no new cases of ITP reported in CAMMS223 in approximately two years.

    Common non-serious adverse events in the trial included infusion-associated reactions in the alemtuzumab patients and flu-like symptoms in patients using Rebif. Alemtuzumab-treated patients were more likely than Rebif patients to experience infections, particularly of the upper respiratory tract; infections were predominantly mild to moderate in severity and there were no life-threatening or fatal infections. Though alemtuzumab transiently lowers white blood cell counts, the trial did not show an increased risk of opportunistic infections. Serious infections were infrequent in the alemtuzumab-treated patients. Approximately 23 percent of alemtuzumab-treated patients developed autoimmune thyroid-related adverse events, including Graves’ disease, and were managed using conventional therapies.

    Alemtuzumab is an investigational drug for the treatment of MS and must not be used in MS patients outside of a formal, regulated clinical trial setting in which appropriate patient monitoring measures are in place.

    Source: Genzyme Corporation & Multiple Sclerosis Resource Centre (23/10/08)

    Genzyme and Bayer Schering Pharma AG, Germany to Present New Data on Alemtuzumab in Multiple Sclerosis at ECTRIMS
    Genzyme Corporation and Bayer Schering Pharma AG, Germany announce that important, new clinical data will be presented this weekend from two studies regarding alemtuzumab use in patients with multiple sclerosis (MS) at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) underway in Prague.

    Charcot Award Lecture

    Top-line, three-year data from a completed international, multi-center, Phase 2 clinical trial known as CAMMS223 that compared alemtuzumab with Rebif(R) (interferon beta-1a) for the treatment of multiple sclerosis will be presented on Sunday, Oct. 14 at 10 a.m. The data will be presented by Professor Alastair Compston during the prestigious Charcot Award lecture. The study results, taken at 36 months, compare alemtuzumab-treated patients with Rebif(R)-treated patients in the risk for sustained accumulation of disability and the risk for relapse. The data come from a pre-specified analysis conducted after three years of treatment for 334 patients in the study.

    Details on two poster presentations -- Alemtuzumab Improved Multiple Sclerosis Functional Composite Scores and Delayed Time to First Relapse at 2-Year Interim Analysis Compared to Subcutaneous Interferon Beta 1-a. Sat. October 13 from 3:30-5:00 p.m. Alasdair J. Coles, M.D.

    A further analysis of disability in CAMMS223, as measured by the Multiple Sclerosis Functional Composite Scale (MSFC), will be reported at ECTRIMS. Data from this scale, including quantitative tests on ambulation, manual dexterity, and cognition, will be presented along with new analyses of relapse events. These results build on the two-year analyses of the co-primary endpoints presented at the American Academy of Neurology annual meeting in May, 2007, which demonstrated that the risk of sustained accumulation of disability as well as the annualized relapse rate were markedly reduced in alemtuzumab-treated patients compared to Rebif-treated patients. Data from CAMMS223 provide the rationale for the newly initiated Phase 3 CARE-MS I clinical trial in untreated patients with relapsing-remitting multiple sclerosis.

    -- Two-year Results with Alemtuzumab in Patients with Active Relapsing- Remitting Multiple Sclerosis Who Have Failed Licensed Beta-Interferon Therapies. Saturday, October 13 from 3:30-5:00 p.m. Ed Fox, M.D.

    In another poster presentation, data from an investigator-sponsored study demonstrate the benefits of alemtuzumab in previously treated MS patients. Data from this two-year study evaluate the effect of two annual cycles of alemtuzumab on patients with relapsing-remitting MS who had failed prior treatment with licensed beta-interferons. Reported at ECTRIMS will be new data on patient functioning as measured by the Multiple Sclerosis Functional Composite Scale cited above. Data from this study provides the basis for the second Phase 3 clinical trial, CARE-MS II, in patients who have continued to relapse while using a licensed therapy. This study is also open to enrollment.

    Source: Genzyme Corporation and Bayer Schering Pharma AG, Germany (12/10/07)

    Genzyme and Bayer Schering Pharma AG, Germany Announce Start of Phase 3 Program with Alemtuzumab for Treatment of Multiple Sclerosis
    Genzyme Corporation and Bayer Schering Pharma AG, Germany today announced that the first patient has been treated in the first of two planned Phase 3 trials examining the safety and efficacy of alemtuzumab for the treatment of multiple sclerosis (MS).

    The CARE-MS I trial (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis), a randomised, rater-blinded study, will compare alemtuzumab to Rebif(R) (interferon beta-1a) in patients with relapsing- remitting multiple sclerosis (MS). Alemtuzumab will be given in two annual cycles; Rebif will be administered three times per week. The CARE-MS I study will include patients who have been diagnosed with relapsing-remitting MS but who have not yet begun treatment with any MS drug. CARE-MS II is scheduled to begin soon and will enroll patients who have continued to experience relapse episodes while on currently available disease-modifying therapies.

    Initiation of this Phase 3 program follows the successful completion of the initial treatment period in the Phase 2 trial. Interim results from the Phase 2 trial indicated that alemtuzumab-treated patients experienced a statistically significant reduction compared with Rebif-treated patients in the risk for sustained accumulation of disability and the risk for relapse for 24 months. Results of the primary outcomes from this trial at 36 months are expected to be presented on Oct. 14 by Professor Alastair Compston during the Charcot Award lecture at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis, in Prague.

    The CARE-MS I study will enroll up to 525 patients at approximately 60 medical centers throughout North America, Australia, Latin America, and Europe, and will again compare alemtuzumab-treated patients to Rebif-treated patients according to two co-primary endpoints: the time to sustained accumulation of disability, and the annualized relapse rate. Alemtuzumab will be dosed at 12 mg/day for five days by daily IV infusion, with a second dosing 12 months later of 12 mg/day for three days. All patients will be followed from their entry into the trial until two years from the date that the last patient is randomized to treatment. Alemtuzumab-treated patients will continue to have safety evaluations for at least three years after the last course of treatment. The companies anticipate filing for marketing approval of alemtuzumab for the treatment of MS in 2011.

    Alemtuzumab is an investigational drug for the treatment of MS and must not be used outside of a formal clinical trial setting in MS patients. Physicians or patients seeking additional information about the CARE-MS I trial should contact Genzyme Medical Information at 1-800-745-4447, option 2 in the United States, + 31 35 6991499 in Europe

    About Alemtuzumab

    Alemtuzumab is licensed in the United States as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL), and outside of the U.S. for the treatment of B-CLL in patients who have been treated with alkylating agents and who have failed fludarabine therapy. The product was launched in its oncology indication in 2001 in the US, where it is marketed by Bayer HealthCare Pharmaceuticals Inc. as Campath(R), and in Europe, where it is named MabCampath(R).

    Alemtuzumab is a humanized monoclonal antibody that binds to a specific target, CD52, on cell surfaces and directs the body's immune system to destroy those cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-CLL.

    Genzyme and Bayer Schering Pharma AG, Germany are co-developing alemtuzumab in oncology, multiple sclerosis and other indications. Bayer Schering Pharma AG, Germany holds exclusive worldwide marketing and distribution rights to alemtuzumab.

    Campath has a boxed warning which includes information on cytopenias, infusion reactions, and infections. The most commonly reported adverse reactions in patients with B-CLL were infusion reactions (fever, chills, hypotension, urticaria, nausea, rash, tachycardia, dyspnea), cytopenias (neutropenia, lymphopenia, thrombocytopenia, anemia), and infections (CMV viremia, CMV infection, other infections). In clinical trials, the frequency of infusion reactions was highest in the first week of treatment. Other commonly reported adverse reactions include vomiting, abdominal pain, insomnia and anxiety. The most commonly reported serious adverse reactions are cytopenias, infusion reactions, and immunosuppression/infections.

    Source: Genzyme Corporation and Bayer Schering Pharma AG, Germany (26/09/07)

    Genzyme gets OK to resume testing of MS drug
    Patient in trial died of bleeding in the brain.

    The Food and Drug Administration will allow Genzyme Corp. to continue human tests of a new multiple sclerosis drug that caused a fatal bleeding disease in one trial patient, the company said yesterday.

    The drug, Campath , is a cancer treatment that has showed promise as a once-a-year infusion for multiple sclerosis patients.

    Compared to a standard MS drug, Campath sharply reduced the number of disabling relapses suffered by patients in a clinical trial. But in 2005, Genzyme disclosed that one patient on Campath had died of bleeding in the brain. The Cambridge company voluntarily suspended its clinical testing of Campath and put a tight surveillance system in place to watch for symptoms of the bleeding disorder.

    At a meeting of financial analysts in Boston yesterday, a Genyzme executive said the FDA had lifted the suspension. He said the clinical trial so far has yielded five other cases of the bleeding disorder, called immune thrombocytopenic purpura , or ITP. All of those patients were treated and recovered. With early detection and treatment, the problem amounts to a "manageable risk" for Campath patients, said the company.

    Although the trial was effectively complete before the suspension, the lifting of the suspension allows Genzyme to move ahead in discussions with the FDA on two larger trials of Campath. Genzyme expects to launch those trials later this year.

    Source: Boston.com © 2007 The New York Times Company (17/05/07)

    Genzyme and Bayer HealthCare Announce Detailed Interim Two-Year Alemtuzumab in Multiple Sclerosis Data Presented at AAN
    Interim analysis of Phase 2 comparative study showed significant results in favour of alemtuzumab versus Rebif(R).

    Genzyme Corporation and Bayer HealthCare Pharmaceutical today announced detailed interim results from the CAMMS223 Phase 2 study. This interim analysis of all patient data through at least twenty-four months from the start of the study for all patients showed that a once-yearly cycle of alemtuzumab treatment had a statistically significant impact on reducing the frequency of relapses and the sustained accumulation of disability in early active relapsing remitting multiple sclerosis (RRMS) patients compared to Rebif® (interferon beta-1a).

    The data were presented yesterday at the 59th Annual Meeting of the American Academy of Neurology (AAN) in Boston by Dr. Alasdair J. Coles, Ph.D., MRCP, Addenbrooke's Hospital, University of Cambridge, United Kingdom. This is the first time that an analysis of the primary and secondary endpoints has been presented in full.

    Dr. Coles' presentation showed patients taking alemtuzumab at the high dose experienced an 87 percent reduction in the risk for relapse (p<0.0001) and a 66 percent reduction in the risk for progression of clinically significant disability (p<0.0098) when compared to patients treated with Rebif. At the low dose, patients taking alemtuzumab experienced similar results, with a 72 percent reduction in the risk for relapse (p<0.0001) and an 88 percent reduction in the risk for progression of clinically significant disability (p<0.0008) compared with patients treated with Rebif. Patients in both alemtuzumab arms also achieved a statistically significant reduction in disability compared with their pre-treatment baseline, as measured by their Extended Disability Status Scale (EDSS) scores.

    "Although several therapies are already available to treat MS, patients still face an unmet need for more effective treatment that further stabilises disability," said Principal Investigator Professor D. Alastair S. Compston, MBBS, Ph.D., FRCP, FMedSci, Addenbrooke's Hospital, University of Cambridge, United Kingdom. "The large two-year reductions in the risk of relapse and sustained accumulation of disability seen in these interim results are impressive, and potentially very encouraging for the many people worldwide who currently face an uncertain future with this devastating disease and for their treating physicians."

    As previously announced, dosing of alemtuzumab in this study was voluntarily suspended in September 2005 after three cases of immune thrombocytopenic purpura (ITP) were reported, the first of which resulted in a fatality. The U.S. Food and Drug Administration (FDA) subsequently placed the study on clinical hold. To date, six of the 216 (2.8 percent) alemtuzumab- treated patients in the CAMMS223 study have developed ITP. ITP is a disorder characterised by a low platelet count and corresponding increased risk of uncontrolled bleeding. Though potentially serious, ITP can be detected and monitored through blood tests, and is usually treatable.

    At the time of the dosing suspension, most patients had received two cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm continued without interruption. Alemtuzumab re-dosing in the trial remains on clinical hold in the United States, and active discussions are underway with regulatory authorities regarding the clinical development program. Significant progress has been made toward the initiation of two planned Phase 3 clinical trials, one that will include previously untreated patients and one that will involve patients receiving an approved therapy whose disease remains active. These Phase 3 studies are expected to begin this year, following FDA clearance. Alemtuzumab is an investigational drug for the treatment of MS. Alemtuzumab should not be used in MS outside of the formal clinical trial setting so that patient safety, including the risk of ITP, can be monitored.

    Phase 2 Study Details

    The open-label, rater-blinded, randomised study enrolled 334 treatment- naïve patients with early, active, RRMS. The trial compares the safety and efficacy of alemtuzumab to Rebif. This is the first time that a potential new therapy for multiple sclerosis has undergone a prospective, controlled, multi- year, head-to-head comparison to a recommended first-line therapy.

    In the trial, patients with RRMS at 49 medical centers in Europe and in the U.S. were treated with alemtuzumab at one of two doses (12 or 24 mg IV per day for five days at initial treatment, and for three days in the subsequent yearly treatments), or Rebif (44 mcg administered subcutaneously three times per week, as indicated in its product label). Although treating physicians were aware of which treatment patients received, independent (blinded) neurologists assessed the disability efficacy endpoint and performed relapse evaluations.

    Primary endpoints in the trial were the annualised relapse rate and the time to Sustained Accumulation of Disability as measured by an increase in EDSS scores lasting at least six months. The efficacy and safety data analyses were reviewed by an independent Data and Safety Monitoring Board. The final analysis of the primary endpoints in CAMMS223 will be based on data through three years in all patients.

    In addition to the results of the co-primary endpoints outlined above, Dr. Coles presented the interim results of the change from baseline in MRI T2 lesion volume and mean EDSS, which are secondary and tertiary endpoints, respectively. Each of these findings supports the results seen in the primary endpoints.

    Safety Results

    In the comparison of safety parameters of alemtuzumab vs. Rebif, a greater number of serious adverse events (a subset of total adverse events) were reported in patients receiving Rebif than in the two alemtuzumab dose groups combined. Most of these were associated with patients who were hospitalised for treatment of their MS.

    The majority of adverse events (93 percent) in all three arms, including infusion-associated adverse events, were mild-to-moderate in intensity. The total number of adverse events was approximately twice as high in each of the alemtuzumab-treated arms as in the Rebif-treated arm, primarily due to the high number of infusion-associated adverse events. Excluding infusion- associated adverse events (i.e., those occurring within 48 hours of an infusion), the incidence of adverse events was similar across the three arms.

    To date, a total of six of 216 (2.8 percent) alemtuzumab-treated patients in the CAMMS223 study have developed ITP. In the initial case, symptoms of ITP were experienced but not recognised in time to seek prompt medical attention. After that case, the sponsor notified investigators and patients of the risk of ITP, and a Patient Monitoring Program for ITP was implemented in CAMMS223. The other five ITP patients were diagnosed promptly, responded well to medical treatment, and have been stable without ongoing treatment for ITP for between five and thirteen months. No new cases of ITP have been reported in the study since September 2006. A presentation of updated ITP information will be made at the AAN conference by Herman Sullivan, MD on Wednesday, May 2, at 4:30PM EDT.

    Additionally, the proportion of patients with thyroid-related clinical adverse events after alemtuzumab treatment was 16.2 percent vs. 1.9 percent after Rebif treatment. Thyroid adverse experiences were substantially less common in the two years after alemtuzumab treatment than in prior studies of the product in MS patients. A poster presentation of updated thyroid autoimmunity information will be made by Dr. Coles on Thursday, May 3.

    About Alemtuzumab

    Genzyme is conducting the clinical development program of alemtuzumab in multiple sclerosis. Bayer HealthCare holds exclusive worldwide marketing and distribution rights to alemtuzumab and participates with Genzyme in the design of clinical protocols and conduct of activities for the development of alemtuzumab for the treatment of MS. Alemtuzumab is an investigational drug for the treatment of MS, and should not be used outside of the formal clinical trial setting.

    Alemtuzumab was approved in 2001 and is marketed outside the United States as MabCampath® and in the U.S. by Bayer HealthCare Pharmaceuticals Inc., as Campath®. The product is indicated for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Determination of the effectiveness of Campath is based on overall response rates. Comparative, randomised trials demonstrating increased survival or clinical benefit such as improvement in disease-related symptoms have not yet been conducted.

    Alemtuzumab is a humanised monoclonal antibody that binds to a specific target, CD52, on some cells of the immune system, including lymphocytes. When alemtuzumab binds to these cells, it triggers their destruction by the immune system. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-cell Chronic Lymphocytic Leukemia (B-CLL), a malignant disease of B-lymphocytes.

    Campath should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Campath has a boxed warning which includes events of hematologic toxicity, infusion reactions, and infections/opportunistic infections.

    Campath is contraindicated in patients who have active systemic infections, underlying immunodeficiency (e.g., seropositive for HIV), or known Type 1 hypersensitivity or anaphylactic reactions to Campath or to any one of its components.

    The most commonly reported infusion-related adverse events in patients with B-CLL were rigors, drug-related fever, nausea, vomiting, and hypotension. Hematologic toxicities included pancytopenia/marrow hypoplasia, anemia, thrombocytopenia, neutropenia, and profound lymphopenia, and should be monitored. Infections reported included sepsis, pneumonia, and opportunistic infections such as CMV, candidiasis, aspergillosis, and mucormycosis.

    Source: Genzyme Corporation (03/05/07)

    Genzyme Reports Interim Results From Trial of Campath(R) for Multiple Sclerosis
    Genzyme Corporation today announced two-year interim results from a Phase 2 trial comparing Campath(R) (alemtuzumab) with Rebif(R) (interferon beta-1a) for the treatment of multiple sclerosis. The results derive from a pre-specified analysis conducted after two years of treatment for 334 patients in the planned three-year trial. This review was conducted in conjunction with an independent data and safety monitoring board.

    As previously announced, dosing of alemtuzumab in this study was suspended in September 2005 after three patients developed immune thrombocytopenic purpura (ITP), a treatable condition in which patients experience a low platelet count as a result of an immune response directed against the platelets. At that time, most patients had received two cycles of therapy with alemtuzumab. Treatment with Rebif in the control arm has continued without interruption. The trial remains on clinical hold in the United States, and Genzyme is working closely with clinical investigators and regulatory agencies to complete the study and ensure that the risk of ITP is well understood and managed. The company discourages physicians and patients from using alemtuzumab for MS outside of a clinical trial setting in which procedures are in place for managing ITP risk.

    Efficacy Results

    Analysis of the first co-primary endpoint showed that patients taking alemtuzumab at high and low doses experienced at least a 75 percent reduction in the risk for relapse after at least two years of follow up when compared to patients treated with interferon beta-1a. This difference was statistically significant in favor of the alemtuzumab patients at both high and low doses, with a p-value less than the pre-specified value (p=0.00328) assigned for the two-year interim analysis.

    Analysis of the other co-primary endpoint showed that patients taking alemtuzumab at high and low doses experienced at least a 65 percent reduction in the risk for progression of clinically significant disability when compared to patients treated with interferon beta-1a. This difference was statistically significant in favor of the alemtuzumab patients at both high and low doses, with a p-value less than the pre-specified value (p=0.01194) assigned for the two-year interim analysis.

    Results of additional secondary and tertiary efficacy endpoints, including MRI data, functional assessments, and quality of life measures, support the findings seen in the co-primary endpoints.

    "These results continue to demonstrate that alemtuzumab has great potential to make a meaningful impact on the treatment of multiple sclerosis," said Richard A. Moscicki, MD, chief medical officer for Genzyme. "We will work with regulatory agencies in the United States and Europe, as well as our clinical investigators, to successfully complete this important trial and to prepare for the initiation of a Phase 3 trial in the first half of 2007."

    Genzyme has requested a meeting with the U.S. Food and Drug Administration to present these data and to address the next steps in the development of alemtuzumab. The company has already received scientific advice from the European Medicines Agency for moving forward with a Phase 3 study.

    Safety Results and Risk Management

    Dosing of alemtuzumab in this study was suspended in the United States in September 2005 after three patients were diagnosed with ITP. The first patient to present with ITP died from the disease. Genzyme immediately implemented enhanced monitoring for ITP and has since created a comprehensive risk management plan to help physicians and patients participating in the trial detect ITP early and minimise the risk of complications. These efforts have been effective and have enabled the identification of all five additional patients with ITP symptoms. All patients requiring medical treatment for ITP have responded well. To date, a total of six patients have been diagnosed with ITP in this trial.

    Other than ITP, serious adverse events related to treatment occurred among four patients treated with the low dose of alemtuzumab and four treated with the high dose. Two patients treated with interferon beta-1a experienced serious adverse events related to treatment. Common non-serious adverse events included infusion reactions in the alemtuzumab patients and flu-like symptoms in patients using interferon beta-1a. The incidence of all thyroid adverse events, including Graves' disease, was less than expected compared to reports in the literature on the use of Campath in MS. Safety information from the study related both to ITP and thyroid disorders will be presented in two weeks at the annual meeting of the European Committee for Treatment and Research in Multiple Sclerosis.

    Phase 2 Trial Design

    The phase 2 trial randomised 334 patients with active relapsing-remitting multiple sclerosis at 49 medical centers in Europe and the United States. Patients in the trial were treated with alemtuzumab at one of two doses (12 or 24/mg per day for five days at initial treatment, and three days of re-treatment), or interferon beta-1a (44 mcg administered three times per week, as indicated in its product label). The alemtuzumab regimen was administered once per year by intravenous infusion, while the interferon beta-1a regimen was administered three times per week by subcutaneous injection. The randomised trial compares the safety and efficacy of alemtuzumab with interferon beta-1a using two primary endpoints: the rate of relapse of MS symptoms, and the time to progression of clinically significant disability (time to Sustained Accumulated Disability over six months as measured by Expanded Disability Status Scale [EDSS]). Although treating physicians are aware of which treatment patients received, independent (blinded) neurologists assessed the disability efficacy endpoint.

    About Campath

    Campath (alemtuzumab), is indicated in the United States for the treatment of B-cell chronic lymphocytic leukemia (B-CLL) in patients who have been treated with alkylating agents and who have failed fludarabine therapy. Campath continues to be available for its labeled indication in leukemia. Determination of the effectiveness of Campath is based on overall response rates. A randomised, controlled phase 3 trial demonstrating clinical benefits in previously untreated patients with B-CLL has been completed, and final safety and efficacy results have been submitted for presentation at a medical meeting later this year. Campath is a humanised monoclonal antibody that binds to a specific target, CD52, on cell surfaces directing the body's immune system to destroy malignant cells. It is the first and only monoclonal antibody approved by the FDA for the treatment of patients with B-CLL.

    Genzyme is developing alemtuzumab in oncology, multiple sclerosis and other indications. Schering AG holds exclusive worldwide marketing and distribution rights to Campath. The product is marketed in the U.S. by Berlex Laboratories, a U.S. affiliate of Schering AG. Campath was launched in the U.S. in June 2001, and in Europe, where it is named MabCampath(R), in August 2001.

    Source: PRNewswire-FirstCall (14/02/06)

    Uncertainty Dogs Campath for MS
    Sometimes the news about an experimental treatment seems almost too good to be true. That seems to be the case for Campath, the monoclonal antibody drug that, in MS, showed a promising ability to control the immune system and slow down active disease in early relapsing-remitting MS.

    Complications

    A three-year trial comparing Campath (alemtuzumab) with Rebif (interferon beta-Ia) was temporarily suspended after one year when nine people taking Campath developed serious side effects according to a press release from manufacturers Genzyme Corporation and Schering AG Germany. Three people developed severe idiopathic thrombocytopenic purpura (ITP), a condition in which low levels of blood platelets can lead to abnormal bleeding. One person died of ITP and another person died of unknown causes. There also was one case of listeria meningitis (a serious infection of the membrane covering the brain and spinal cord) and two people developed Graves' disease, an autoimmune thyroid condition that requires lifetime maintenance. In fact, in earlier Campath studies involving people with MS, there was a 26% incidence of developing Graves' disease.

    At the start of the trial, 334 people were randomly selected to receive either Campath as a one-time-a year, five-day IV infusion, or Rebif. Campath's developers reported that after one year, the 217 people receiving both high and low doses of Campath had 75% fewer relapses than were experienced by the group taking Rebif.

    Wait and see

    These are strong results. However, there won't be any further Campath treatments for MS until patient safety protocols are established. At present, Campath is used for the treatment of one type of leukemia. The companies emphasize that Campath should not be used for MS at this time. The study will continue to follow participants for a second year. We'll keep you posted on future developments.

    Source: Inside MS Copyright National Multiple Sclerosis Society Feb/Mar 2006 (14/02/06)

    Genzyme gets FDA warning on MS treatment
    Genzyme Corp. suffered another setback to its bid to use its leukemia drug Campath to treat multiple sclerosis.

    The U.S. Food and Drug Administration issued a health alert on Wednesday over use of the drug in a clinical trial to treat multiple sclerosis, according Reuters.

    Genzyme in September already suspended a clinical test after a patient died from abnormal bleeding and two others developed the condition. Genzyme remains in talks with the FDA about how to resume clinical trials that the company hoped to continue in the first half of 2006.

    A Genzyme spokesman cited in the Reuters report said the alert may be intended for doctors who prescribe the treatment even though it isn't approved yet for MS.

    Cambridge, Mass.-based Genzyme is jointly developing the drug with Germany's Schering AG. Campath has been approved since 2001 to treat leukemia but it carries a number of warnings relating to serious and potentially fatal side effects, including the condition that erupted during the multiple sclerosis study.

    Source:  Boston Business Journal (01/12/05)

    Schering shares fall on FDA alert - bad news for Campath

    Shares in German drugmaker Schering fell as much as 1.1 percent on Thursday after U.S. regulators issued a health alert over its Campath drug in a trial to treat multiple sclerosis.

    Campath is approved to treat a type of blood cancer, but in a study on multiple sclerosis, three patients developed a severe blood disorder and one of them died, the FDA said.

    The company initially reported the serious side effect in September and put the trial on hold.

    "This is the official posting on the FDA website that pertains exactly to the announcement we made in September. We are still in discussions with the FDA," said a Schering spokesman.

    Analysts said the FDA warning was anticipated, but the focus would now be on the future of the drug to treat multiple sclerosis.

    "This is the expected official warning," said MM Warburg analyst Ulrich Huwald. "It will now be interesting to see if Schering can go ahead with Phase III trials."

    Another analyst, who declined to be named, said: "The FDA obviously wants to spell out the risks to doctors. It's now a challenge to Schering to minimize the risks in future trials so as to get a line extension for multiple sclerosis.

    "It's difficult to say what impact it will have on the main use in blood cancer -- it will probably be small," he said.

    In its alert, the FDA said patients should talk to their doctors if they were concerned about taking the drug. The agency added it had not reached a final conclusion about the trial's data.

    The patients in question developed idiopathic thrombocytopenic purpura, a disorder that causes the body to attack its own platelets and is already mentioned on the drug's label. (07/12/05)

    Three MS patients in Campath trial get blood disorder

    Genzyme Corp. said yesterday that it has halted an experimental treatment for multiple sclerosis after three patients contracted a rare bleeding disorder and one of them died.

    The company was testing Campath, a drug currently used to treat leukemia, on patients with multiple sclerosis.

    Campath appeared to alleviate MS symptoms and showed signs that it might be able to halt long-term damage from the disease. But in some patients, it also triggered a dangerous drop in blood platelets, the cells that help the body clot and seal wounds.

    Three of 219 MS patients given the drug were diagnosed with the blood condition, called idiopathic thrombocytopenic purpura. Genzyme said it will not give Campath to patients until the safety issue can be resolved.

    ''Multiple sclerosis is a very serious disease, and you don't want any deaths," Dr. Richard Moscicki, the Cambridge company's chief medical officer, said yesterday.

    Moscicki said the patient who died had shown symptoms of the condition for a month without seeking medical care. The other two patients were diagnosed more quickly and are responding to treatment, he said.

    Genzyme said it intends to continue testing the drug after working with regulators to improve the safety of the trials, but it will monitor patients more closely and instruct them to look for symptoms of the blood condition.

    Campath is one of two cancer drugs Genzyme acquired last year when it bought Ilex Oncology Inc., a Texas company, for $1 billion. Ilex had already started the multiple sclerosis trial. Under the deal, Campath is owned by Genzyme but sold by the German drug company Schering AG.

    The test was designed to measure the effectiveness of Campath in comparison with Rebif, a drug now on the market to treat MS symptoms, which can include numbness, vision problems, and disorientation.

    After analyzing data from the first year of the planned three-year trial, Genzyme said patients on Campath were only one-quarter as likely to have a relapse of symptoms as those taking Rebif. It also showed some signs of slowing long-term damage, though not enough to be statistically significant.

    Campath is approved only to treat a rare cancer called B-cell chronic lymphocytic leukemia. If it is approved to treat multiple sclerosis, sales could increase dramatically. The National Multiple Sclerosis Society estimates that approximately 400,000 people in the United States have MS.

    An analyst said yesterday that the news was unlikely to have an immediate effect on the company's financial picture because Campath probably would not receive approval as an MS treatment before 2009.

    ''I think the data are intriguing because the efficacy seemed to be very strong," said Phil Nadeau, a biotechnology analyst for SG Cowen. ''It's now up to the company to better define the safety of the compound."

    © Copyright 2005 Globe Newspaper Company.(17/12/05)

    © Multiple Sclerosis Resource Centre

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