The different classes of Disease Modifying Drugs for Multiple Sclerosis are:

• Beta interferon 1a - known by the trade names AVONEX® and REBIF® and BIFERONEX®
• Beta interferon 1b - known by the trade name  BETASERON®
• Glatiramer acetate  - known by the trade name COPAXONE^®
• Natalizumab - known by the trade name TYSABRI^®

To access the latest ongoing research for each class of drug just click on the links below

• AVONEX^®,REBIF^® and BIFERONEX^®
• BETASERON^® (BETAFERON^®)
• COPAXONE^®
• TYSABRI^®

You can access all the latest general news about Disease Modifying Drugs by going the Disease Modifying Drugs Ongoing News pages.

Beta-interferons in MS: A single centre experience in India

Abstract   

Background: Indian-Asian multiple sclerosis behaves somewhat differently from Western disease. It is not known if the response to β-interferon is also different.

Aim: To demonstrate the decrease in relapses with β-interferon in Indian patients with multiple sclerosis.

Patients and Methods: Patients with relapsing-remitting or secondary progressive multiple sclerosis with at least two relapses were started on β-interferon.

Results: Sixteen patients were followed up for a period of 1-3 years. Fifteen had relapsing-remitting multiple sclerosis (MS). The mean number of relapses in these patients before interferons were started was 3.4. The mean yearly relapse rate was 1.3. The mean Kurtzke Expanded Disability Status Scale (EDSS) at the start of β-interferon therapy in relapsing-remitting MS was 1.7. Ten of these patients were on Avonex® (interferon β1a) and six (including the patient with secondary progressive MS) were on Betaferon® (interferon β1b). On follow-up, three patients (two on Avonex® and one on Betaferon® ) had relapses.

The respective β-interferon being received by these patients was continued, with no further relapses.

The remaining patients had no relapse or clinical or MRI progression after starting the drug.

The side effect profile of the drug in these patients was favourable; although nearly all developed fever on the first day of the injection, only 50% of the patients continued to have fever after 3 months. Two patients developed psychiatric symptoms, requiring discontinuation of the drug.

Conclusion: Our prospective follow-up study shows that β-interferons are safe and effective in Indian patients with relapsing-remitting or secondary progressive MS.

Salil Gupta, R Varadarajulu, RK Ganjoo
Department of Neurology, Command Hospital Air Force, Bangalore, India

Source: Annals of Indian Academy of Neurology © 2006 - 2010 Annals of Indian Academy of Neurology (06/07/10)

New data demonstrated significant impact of access to neutralizing antibody testing on MS treatment management

Teva Neuroscience announced results at the 62nd American Academy of Neurology Annual Meeting which demonstrated that eliminating barriers to neutralizing antibodies (NAbs) testing significantly impacted multiple sclerosis (MS) treatment choices in patients receiving interferon beta (IFNβ) therapies.

"One of the most common barriers for NAbs testing is the current lack of reimbursement for the tests," said lead study investigator, Dr. Barbara Green, Director West County MS Center, St. John's Mercy Medical Center. "Our results indicate that access to NAbs testing may be an important consideration surrounding MS therapy decisions."

IFNβ therapies for MS are associated with the development of NAbs in some patients. NAbs are antibodies produced by the body, which react with a foreign agent and destroy it or inhibit its effect¹. This study explored whether removing barriers to antibody testing impacted treatment decisions for MS patients receiving IFNβ therapies (1-4 years).

Currently, only Europe has guidelines recommending that IFNβ patients be tested at 12 and 24 months for NAbs. The guidelines also recommend that testing should be repeated in patients who test positive for NAbs, and therapy with IFNβ should be discontinued in patients with high titers of NAbs sustained at repeated measurements at three to six month intervals.²

Patients randomized to both arms (regularly scheduled antibody testing, n=651 and usual care, n=565) of this 12-month, open-label study had a mean disease duration of 8.5 years and mean interferon treatment duration of two years. The proportion of therapy change was significantly different between the two arms (p<0.0069). There was also a significant difference between arms on the number of patients starting one or more courses of corticosteroids for relapses (p=0.0022) and starting glatiramer acetate (p=0.0028). While clinical worsening was the most frequent reason for therapy change in both arms, positive NAbs results represented the second most frequent indicated reason in the NAbs testing arm.

This study was sponsored by Teva Neuroscience.

About the Study

MS patients on IFNβs (1-4 years) were enrolled in a 12-month, open-label study. Patients were randomized into either Regularly Scheduled Antibody Testing arm (3 binding antibodies [BAbs] and NAb tests within 9 months) or Usual Care arm (blinded BAbs and NAbs testing at baseline and usual patient care). Both arms had optional testing at 12 months. BAb and NAb levels were measured by ELISA and viral cytopathic effect (CPE) assays, respectively.

Patients in the Antibody Testing arm (n=651) and Usual Care arm (n=565) had a mean disease duration of 8.5 years, and a mean of 2 years on interferons; 71% on IFNβ 1a SC, 28% on IFNβ 1b. At baseline, 37% of IFNβ-1a SC patients and 47% of IFNβ-1b were BAb +; 19% and 22% were NAb+, respectively. Proportion of therapy change was significantly different between the two arms; 19.5% of patients in Antibody Testing arm and 14.2% of patients in Usual Care arm had a therapy change (p<0.0069).

References

¹ Stachowiak, Julie (August 15 2008). Julia Stachowiak "Neutralizing Antibodies and Disease-Modifying Therapies for Multiple Sclerosis". About.com. http://ms.about.com/od/treatments/a/cmp_nabs.htm Julia Stachowiak. Retrieved March 9, 2010.

² Sorensen PS, Deisenhammer F, Duda P, Hohlfeld R, Myhr KM, Palace J, Polman C, Pozzilli C, Ross C, EFNS Task Force on Anti-IFN-beta Antibodies in Multiple Sclerosis. Guidelines on use of anti-IFN-beta antibody measurements in multiple sclerosis: report of an EFNS Task Force on IFN-beta antibodies in multiple sclerosis. Eur J Neurol  2005 Nov;12(11):817-27.

Source: Teva Neuroscience (15/04/10)

Study uses MRI scans to track effectiveness of multiple sclerosis drugs

A long-term brain scan comparison of two leading drug treatments for early-stage multiple sclerosis has found that one, Betaseron, more effectively reduces the formation of "chronic black holes" in the brain.

The study by researchers at the University of Medicine and Dentistry of New Jersey-New Jersey Medical School is the first to use monthly MRI scans to document the progression of brain lesions associated with the disease, according to its authors.

Although the findings still must be confirmed, they do offer provocative insight into early brain changes with MS, according to Patricia O'Looney, vice president of Biomedical Research for the National Multiple Sclerosis Society.

"While we can't be sure about the relationship between black holes and MS symptoms, excellent research such as this contributes to understanding of MS," O'Looney said. "It is an incredibly hopeful time in the treatment of the disease."

The black holes are believed to represent areas where nerve loss -- the most severe and irreversible brain damage in MS -- has occurred. Both Betaseron and Copaxone, the two drugs compared in the study, reduce the number of permanent black holes.

UMDNJ-NJMS researchers found, however, that while 15.2 percent of brain lesions converted to black holes for patients on Copaxone, 9.8 percent did on Betaseron, said neurology professor Stuart D. Cook, an author of the study.

"This is the first and largest head-to-head trial by sensitive monthly MRI technology comparing the two medicines," said Cook, whose findings have been published online by the Journal of Neurology, Neurosurgery & Psychiatry. "It has produced a wealth of information about the natural history of multiple sclerosis during treatment with first line MS therapies."

Multiples sclerosis is an unpredictable, often disabling progressive disease of the central nervous system affecting an estimated 400,000 in the U.S. and 2.5 million worldwide, most of them between the ages of 20 and 50. Symptoms range from numbness and tingling to blindness and paralysis and, in rare cases, death.

Symptoms, which in early stages can come and go, are caused by the destruction of myelin, the protective insulation surrounding nerve fibers of the central nervous system. The nerve fibers are also damaged. Lesions can heal themselves in early stages of the disease, experts say, but are believed to eventually result in scarring and black holes.

The UMDNJ-NJMS study followed 75 patients in northern New Jersey who were either newly diagnosed or in the relapsing-remitting form of MS, where symptoms can come and go. Over a two-year period, the patients were given monthly MRI scans enhanced by dye.

The scans showed patients developed lesions sooner than experts thought and happened more often than expected. Cook said the scans also established that MS patients had an average of 30 new lesions to one clinical symptom.

Previous studies have shown that the four common drug treatments for this MS phase are all effective. Three, Betaseron , Avonex and Rebif, are all interferon based. Copaxone is a different class, glatiramer acetate.

As the UMDNJ study progressed, however, Cook said researchers found that as new lesions developed into black holes, the Betaseron-treated patients had fewer conversions. Avonex and Rebif were not included in the study, which was sponsored by Bayer HealthCare, the distributor of Betaseron.

Cook noted, however, the study was initiated by the university, not Bayer.

Source: NJ.com © 2009 New Jersey On-Line (18/08/09)

NIH deepens investment in combination study Of MS drugs

The first large-scale "CombiRX" clinical trial testing the combined use of FDA-approved interferon beta-1a(Avonex®) and glatiramer acetate (Copaxone®) to treat relapsing-remitting MS has just received a $19-million renewal grant from the National Institutes of Health. This is the largest MS trial ever supported by the NIH, with a cumulative investment of more than $44 million. The long-term trial is led by principal investigator Fred Lublin, MD, (Corinne Goldsmith Dickinson Multiple Sclerosis Center at Mount Sinai School of Medicine, New York, NY).

The study is now fully enrolled, with more than 1,000 participants at 67 medical centers across the United States and Canada. Dr. Lublin is a member of the National Board of Directors of the National MS Society and the Society's National Clinical Advisory Board and the New York City Chapter Clinical Advisory Committee.

Combination therapy is being compared to the use of either agent alone for 36 months. All participants are receiving at least one active medication and there is not a placebo-only treatment arm. Each of these treatments is approved by the U.S. Food and Drug Administration for the treatment of relapsing MS. A previous, smaller pilot trial of the combination therapy suggested it was safe and warranted further study.

An important ancillary study to this trial, the NIH-sponsored biomarker project, is examining genetic and other biological markers at baseline and at a minimum of one additional point during the study. The hope is that these biological markers will provide a means for identifying, in the future, those patients with more aggressive disease as well as those who respond or fail to respond to therapy. Such markers would have considerable value in the management of MS.

Source: Medical News Today © 2009 MediLexicon International Ltd (27/07/09)

Disease-modifying drugs improve cognitive function in Multiple Sclerosis patients

Patients with relapsing-remitting multiple sclerosis (RRMS) who receive glatiramer acetate (GA) or interferon (IFN) beta show a reduction in cognitive impairment and relative stability of cognitive and affective variables at 2 years, according to the results of an observational study presented at the 19th Meeting of the European Neurological Society (ENS).

The aim of the observational study was to evaluate the long-term effects of first-line disease-modifying therapies with GA or IFN beta on cognitive functions, affective status, fatigue and quality of life in patients with RRMS (ITACA study).

"A total of 752 patients with RRMS and a mean age of 36 years were enrolled in 79 Italian centres," explained principal investigator Monica Falautano, PhD, Functional Unit of Psychology, IRCCS H. San Raffaele Milano, Milan, Italy.

Study patients were treated with either GA or IFN beta.

At baseline and 6, 12, 18, and 24 months, a fatigue and physical disability evaluation was performed.

Cognitive and affective assessments were performed at baseline and 12 and 24 months.

A significant reduction [P < .0001] in cognitive impairment was observed at the 24-month follow-up, Dr. Falautano noted. At baseline, 40% of all patients showed mild cognitive impairment, and 16% showed severe cognitive impairment, which the researchers said was reduced to 30% and 11%, respectively, at 2 years.

A higher proportion of GA than IFN patients had been affected by severe cognitive impairment (20% vs 12%). At the 24-month follow-up, the percentage of severe impairment was reduced to similar amounts in both treatment groups (12% and 10%, respectively).

According to the mean Montgomery-Asberg Depression Rating Scale score, significant depressive symptoms were missing both at baseline and at the 24-month follow-up.

Physical and mental health assessed with the Multiple Sclerosis Quality of Life 54 questionnaire correlated highly significantly at baseline and at the 24-month follow-up (P < .001).

Patients did not report any changes in perception of their quality of life after 2 years of treatment. No changes were observed in Kurtzke's Functional Systems Scores.

"The immunomodulatory treatment may have an impact on cognitive function," Dr. Falautano summarised the primary result of the study. "Nevertheless, a longer follow-up is advisable to confirm our results."

Source: European Neurological Society (29/06/09)

MS disease modifying drugs - are they increasing the risk of cancer?

Current CIHR-funded research: In the first study of its kind, researchers from Canada are examining whether beta-interferon, widely used to treat multiple sclerosis (MS), increases the risk of cancer for MS patients.

"Given the increasing popularity of MS drugs, even a moderate increase in the risk of cancer could translate into a substantial number of new cancer cases," says lead researcher Dr. Helen Tremlett at the University of British Columbia. "Our study will also benefit from its independence from the pharmaceutical industry, which manufactures beta-interferon."

Source: Canadian Institutes of Health Research (17/05/09)

The clinical effect of neutralizing antibodies against interferon-beta is independent of the type of interferon-beta used for patients with relapsing-remitting multiple sclerosis

Objective: To establish whether the clinical effect of neutralizing antibodies (NAbs) against interferon-beta (IFNbeta) depends on the type of IFNbeta (1a or 1b) used for treatment of patients with relapsing-remitting multiple sclerosis (MS).

Introduction: NAbs against IFNbeta-1b appear faster and may be more evenly distributed on IgG subclasses, whereas NAbs against IFNbeta-1a develop more slowly and may be devoid of IgG3. This might cause different clinical responses to NAbs.

Design/patients: All Danish MS-patients who had started first-time treatment with IFNbeta-1a 22 microg s.c tiw (Rebif22) or IFNbeta-1b 250 microg s.c. qod (Betaferon) before January 1st 2003 were included. Relapses were recorded at bi-annual visit.

Methods: We measured NAbs every 12 months using a clinically validated cytopathic effect assay. A blood sample with a neutralizing capacity of 20% or more was considered as NAb-positive. We used a mixed logistic regression analysis in which NAb-status (three levels), IFNbeta-preparation, and time since treatment started were included as explanatory variables, and relapse rate as response variable.

Results: In 1,309 patients, who were observed for 21,958 months, 32.3% were classified as NAb-positive. The odds-ratio (OR) for relapses in NAb-positive months compared with NAb-negative months was 1.25; P = 0.02. The risk of relapses was higher with Betaferon than with Rebif22 (OR 1.26; P < 0.01). The effect of NAb-level on relapses was independent of whether the patients were treated with Betaferon or Rebif22 (P = 0.89) and of time (P = 0.80).

Conclusion: NAbs caused by IFNbeta-1a s.c. do not differ from NAbs caused by IFNbeta-1b in their detrimental clinical effect.

Source: PMID: 19299439 (01/04/09)

New Interferon formulations promise to eliminate injections in Multiple Sclerosis treatment

Nerveda Inc. and Aegis Therapeutics LLC today announced preclinical results from their joint collaboration aimed at developing non-injectable formulations of the beta-interferons. The beta interferons, beta-1a (tradename Rebif(R)), and beta 1b (tradenames Betaseron(R) and Betaferon(R)) are closely related injectable protein drugs in the interferon family that are used to treat both the relapsing-remitting and secondary-progressive forms of multiple sclerosis (MS). The beta interferons are currently administered by subcutaneous injection and have been proven clinically to slow the advance of multiple sclerosis and reduce the frequency of attacks. Current worldwide combined annual sales of Rebif(R), Betaseron(R) and Betaferon(R) are approximately $4 Billion.

Because proteins are large and fragile molecules, they cannot be administered orally and are typically administered by injection. They are often subject to instability due to aggregation of the protein molecules -- particularly upon storage and handling at non-refrigerated temperatures. The resulting protein aggregates are more poorly absorbed into the blood stream upon injection due to their increased size, and induce development of circulating antibodies to interferon in patients that reduce the effectiveness of the drug over time.

Leading medical scientists at Johns Hopkins University, expert in the treatment of neurological diseases, in collaboration with Nerveda and Aegis have applied Aegis' Intravail(R) transmucosal absorption enhancement, and ProTek(R) protein stabilization technologies to address these problems and have demonstrated for the first time that the beta interferons can be administered intranasally to prevent nerve damage in preclinical animal models of multiple sclerosis. In addition, the new formulations were shown to reduce or eliminate the immunogenicity of Betaseron(R) and Rebif(R), administered either by injection or intranasally, while substantially increasing stability in a stress test involving constant agitation at elevated temperatures for extended periods of time.

Dr. Edward Maggio, Ph.D., CEO of Aegis Therapeutics, who participated in the research, said, "since interferons will continue to be the foundation of MS therapy, it is critical that non-invasive delivery options for patients be developed." Maggio also indicated, "the reduction in immunogenicity and the increase in stability also address a significant unmet need of the currently available beta-interferon therapies."

Nerveda plans to begin testing the new formulation in clinical trials in early 2009 in collaboration with clinicians and scientists at John Hopkins University Medical Center and other sites.

* Rebif(R) is a registered trademark of Pfizer, Inc.

* Betaseron(R) is a registered trademark of Bayer Healthcare Pharmaceuticals

* Betaferon(R) is a registered trademark of Bayer Schering Pharma AG

* Intravail(R) and ProTek(R) are registered trademarks of Aegis Therapeutics, LLC

Source: Aegis Therapeutics LLC (12/01/09)

Only half of patients with multiple sclerosis achieve and maintain response to interferon treatment

Regular magnetic resonance imaging (MRI) evaluations show that only about half of patients with multiple sclerosis achieve and sustain a response to treatment with interferon beta over three years, according to a study posted online today that will appear in the January 2009 print issue of Archives of Neurology, one of the JAMA/Archives journals.

Before they develop symptoms of a relapse, patients with multiple sclerosis (MS) develop contrast-enhancing brain lesions that are visible on MRI, according to background information in the article. Worsening of the disease is presumed to follow these relapses. "Many clinical studies have demonstrated the ability of interferon beta to reduce contrast-enhancing lesions," the authors write. "However, little is known regarding the heterogeneity of the MRI response profiles between patients or within an individual patient over time."

Annie W. Chiu, B.S., and colleagues at the National Institute of Neurological Disorders and Stroke, Bethesda, Md., assessed 15 patients with MS who underwent monthly MRIs and clinical examinations during a six-month pretreatment phase and a 36-month treatment phase. During treatment, patients receive injections of 250 micrograms of interferon beta under the skin every other day.

Eight patients (53.3 percent) achieved a 60 percent reduction in the number of lesions at each six-month period and were therefore classified as responders. Of the seven non-responders, three (20 percent) initially experienced a reduction in the total number of lesions but then did not experience further reductions, two (13.3 percent) never reached the 60 percent level of reduction and two (13.3 percent) failed to respond during the first six months but reached and maintained an optimal reduction in lesions of 60 percent or more thereafter. Three patients in the responder group and all seven patients in the non-responder group experienced at least one clinical exacerbation during the treatment phase.

"To our knowledge, our descriptive study provides for the first time a detailed long-term analysis of MRI patterns of patients undergoing long-term interferon beta-1b therapy," the authors conclude. "The results show that on close monthly MRI inspection, approximately half of the patients fail therapy from an MRI perspective."

"Also, we show that an additional small proportion of patients may not be necessarily recognized as MRI non-responders during the first semester [six months] of therapy, and frequent radiological monitoring is advised during the first year of therapy. Multiple MRIs, beyond the first six months of therapy, also disclose a small proportion of patients with a delayed but eventually sustained response to interferon beta and provide compelling information regarding the clinical outcome of patients during the course of a longer trial."

Source: Science Codex (11/11/08)

Bolder BioTechnology receives $1.6 million NIH grant to continue development of Multiple Sclerosis drug

Bolder BioTechnology, Inc. announced today that it has been awarded a $1.6 million Phase II Continuing Renewal Small Business Innovation Research (SBIR) grant, entitled "Long-Acting Beta Interferon for Multiple Sclerosis", from the National Institute of Neurological Disorders and Stroke (NINDS) of The National Institutes of Health (NIH). Receipt of the entire grant award is contingent upon the achievement of certain research milestones.

The new grant award will be used to perform preclinical studies required by the Food and Drug Administration for filing an Investigational New Drug application to begin testing our long-acting beta interferon analog in people. Recombinant beta interferon products have annual worldwide sales of approximately $5 billion, primarily from use of the drugs to treat Multiple Sclerosis.

Multiple Sclerosis is a debilitating neurological disease that affects approximately 400,000 people in the United States and 2.5 million people worldwide. Current commercial beta interferon products are only partially effective and are inconvenient to use because they must be injected frequently, typically for the life of the patient.

"Our long-acting beta interferon analog was designed to provide patients with a more efficacious and easier to use product." said Bolder BioTechnology, Inc.

Source: Arizona Biotech News (16/10/08)

Diplomat specialty pharmacy selected by Teva Neuroscience for therapy optimization study for Multiple Sclerosis (TOP MS)

Diplomat Specialty Pharmacy announced that Teva Neuroscience has selected it to be one of only three sites to participate in a large scale, national Therapy Optimization Study for Multiple Sclerosis (TOP MS).

The goal, of the two year TOP MS study, is to examine the benefits of a specialty pharmacy therapy management program on compliance, adherence and patient outcomes. Targeted patient outcomes will include: Relapses, Disability Progression, Quality of Life, and Work and Usual Activity Participation.

"We are honoured that Teva Neuroscience selected Diplomat to participate in this study," said Phil Hagerman, President and CEO of Diplomat. "I have no doubt that the TOP MS study will validate the benefits of our patient centric model. When we focus on adherence and tolerance, and offer patients a personalized medication program, we can reduce the frequency and severity of relapses and ultimately improve the quality of life."

"Diplomat Specialty Pharmacy was selected to participate in this study because they have shown a commitment to therapy management in MS that is exemplary among Specialty Pharmacies," said MerriKay Oleen-Burkey, Project Leader for the TOP MS Study at Teva Neuroscience.

"This really is a credit to Diplomat's industry leading MS Navigator program that currently benefits physicians and especially MS patients across the country," said Ken Visser, Diplomat's National Accounts Manager for Multiple Sclerosis. "At Diplomat we maximize therapy adherence by enhancing patient education and prescriber communication. Using our exclusive eNAV(TM) patient care software system, we can electronically record and report our patients' therapy and disease. All of this combined amounts to some of the highest patient adherence numbers in the country."

Source: Diplomat Specialty Pharmacy (13/10/08)

No difference among disease-modifying drugs for the long-term Treatment of Multiple Sclerosis

The different disease-modifying drugs available on the market for treatment of relapsing-remitting multiple sclerosis (MS) result in similar rates of disease relapse when examined over the long term, according to a retrospective chart review.

Loren Rolak, MD, The Marshfield Clinic, Marshfield, Wisconsin, presented the results of the study here on September 23 at the American Neurological Association (ANA) 133rd Annual Meeting.

Dr. Rolak and colleagues reviewed the clinical course of 573 patients with relapsing-remitting MS treated with disease modifying agents at The Marshfield Clinic. They evaluated 176 patients for >5 years, 47 patients for >10 years, and 27 patients for >12 years.

Results show that relapse rates (RR) were similar among the 4 disease-modifying therapies: 0.29 with glatiramer acetate subcutaneous (n = 224), 0.32 with beta interferon-1a intramuscular (n = 180), 0.30 with beta interferon -1a subcutaneous (n = 43), and 0.31 with beta interferon-1b subcutaneous (n = 126).

There was no association between major histocompatibility complex class II DR beta 1 (HLA-DRB1) or nitric oxide synthase (NOS2A) genotypes and relapse rate among the different drugs.

"Switching to another drug doesn't matter in terms of relapses; if you fail one drug, switching to another one doesn't result in clinical improvement," Dr. Rolak added.

Dr. Rolak's data also demonstrated similar degrees of disability for patients on the different treatments during follow-up that extended to 12 years. At the onset of follow-up, patients had an Extended Disability Status Scale (EDSS) scores ranging from 1.5 to 2.5. At the end of 12 years, the EDSS scores ranged from 4 to 4.5. EDSS scores with the different drugs were similar at 7, 10, and 12 years.

These results are consistent with recent head-to-head trials that compared these drugs, Dr. Rolak observed. These studies failed to show significant differences in the efficacy of these drugs, he said.

"None of the drugs demonstrate superiority in relapse rate or EDSS when followed for up to 12 years," Dr. Rolak concluded.

Source: [Presentation title: No Difference Among Disease-Modifying Drugs for the Long-Term Treatment of Multiple Sclerosis. Abstract T-103] (25/09/08)

REGARD study: Interferon beta vs glatiramer acetate in relapsing multiple sclerosis

The REGARD ( Rebif vs Glatiramer Acetate in Relapsing MS Disease) study compared interferon beta-1a with glatiramer acetate, both of which are prescribed in patients with relapsing-remitting multiple sclerosis (RRMS).

Patients with RRMS (diagnosed with the McDonald criteria), who had had at least one relapse within the previous 12 months were randomised to subcutaneous interferon beta-1a (44 mcg three times/week, n=386) or subcutaneous glatiramer acetate (20 mg/day, n= 378). The patients were followed for 96 weeks and observed for the primary endpoint, time to first relapse.

The researchers found no difference between the two drugs for the primary endpoint (HR 0.94, 95% CI 0.74 to 1.21; p=0.64). Relapse rates were lower than expected; 126 in the interferon group and 132 in the glatiramer group had one or more relapses.

The researchers found that the overall number and severity of adverse events were similar between the treatments and were not an important cause for discontinuation of the trial.

Source: The Lancet Neurology Early Online Publication (11/09/08)

Modigene wins Israeli grant for interferon-beta-CTP multiple sclerosis research program

Modigene has reported that its Israeli-based R&D subsidiary has received approval for a special grant from the Israeli Office of the Chief Scientist in support of the company's development program for interferon-beta-CTP, its longer-acting version of interferon beta.

The Office of the Chief Scientist (OCS) has approved a special grant to support Modigene's interferon-beta-CTP (IFN-Beta-CTP) program for 2008-2009. The grant will provide cash reimbursements of 40% of expenses paid for IFN-Beta-CTP product development during this period.

Modigene's full IFN-Beta-CTP development program, as submitted to the OCS, is based on an estimated development budget of $25 million for calendar years 2008-2011. IFN-Beta-CTP is currently in preclinical development, with clinical trials expected to begin in 2009.

Under the terms of the grant, Modigene is required to repay the OCS the sum of the grant plus accrued interest through a series of payments that begin only upon successful commercialization of the IFN-Beta-CTP product, or other products developed at the company with its CTP technology.

Interferon beta is a drug used to reduce the frequency and severity of relapses afflicting people suffering from multiple sclerosis, an autoimmune neurological disorder affecting the insulating myelin layers of the brain and spinal cord.

Abraham Havron, CEO of Modigene, said: "This visionary OCS program is particularly attractive for Modigene because it does not require any repayment until the product is generating revenue. We are grateful for this valuable source of non-dilutive capital."

Source: Pharamceutial Business Review ©2008 Progressive Media Group (07/08/08)

Interferon-β increases BAFF levels in multiple sclerosis: implications for B cell autoimmunity

B cells are increasingly recognized as major players in multiple sclerosis pathogenesis. The BAFF/APRIL system is crucial for B cell homoeostasis and may drive B cell-dependent autoimmunity. We asked whether this system is affected by Interferon (IFN)-β therapy.

We analysed transcription of the ligands (BAFF, APRIL, TWE-PRIL) and the corresponding receptors (BAFF-R, TACI and BCMA) by TaqMan-PCR ex vivo in whole blood and in immune cell subsets purified from IFN-β-treated multiple sclerosis patients. Serum BAFF concentrations were determined by ELISA. 

This cross-sectional study involved 107 donors. IFN-β therapy strongly induced BAFF transcription proportionally to the IFN-β biomarker MxA in monocytes and granulocytes in vivo. BAFF serum concentrations were elevated in IFN-β-treated multiple sclerosis patients to a similar level as observed in SLE patients. In cultured PBMC, neutrophils, fibroblasts and astrocytes, BAFF was induced by IFN-β concentrations similar to those reached in vivo in treated multiple sclerosis patients. BAFF turned out to be the main regulated element of the BAFF/APRIL system. 

In untreated multiple sclerosis patients, there was no BAFF increase as compared to healthy controls. Our study reveals a complex situation. We show that IFN-β therapy induces a potent B cell survival factor, BAFF. However, B cell depletion would be desirable at least in some multiple sclerosis patients. 

The systemic induction of BAFF by IFN-β therapy may facilitate the production of various autoantibodies and of IFN-neutralizing antibodies.

Individual MS/NMO patients who have major B cell involvement may benefit less than others from IFN-β therapy, thus explaining interindividual differences of the therapeutic response. 

M. Krumbholz^1,2,*, H. Faber^1,2,*, F. Steinmeyer^1,2, L.-A. Hoffmann², T. Kümpfel², H. Pellkofer², T. Derfuss^1,2, C. Ionescu³, M. Starck³, C. Hafner⁴, R. Hohlfeld^1,2 and E. Meinl^1,2

¹Department of Neuroimmunology, Max Planck Institute of Neurobiology, Martinsried, ²Institute for Clinical Neuroimmunology, Ludwig-Maximilians-Universität, Munich, ³Marianne-Strauß-Klinik, Berg and ⁴Department for Dermatology, University of Regensburg, Regensburg, Germany

Source: Brain 2008 131(6):1455-1463; doi:10.1093/brain/awn077 © 2007 Guarantors of Brain (04/06/08)

New information about multiple sclerosis and disease modifying drugs

According to recent research from the United States, Results from an increasing number of clinical trials with disease-modifying drugs (DMDs) in multiple sclerosis (MS) become available, the challenge for the treating is how to decide on the appropriate therapy for an individual patient. An International Working Group for Treatment Optimization in MS met to consider how the principles of evidence-based medicine (EBM) should be used to assess the current best evidence regarding the treatment of MS.

"This report summarizes the outcome from the workshop at which this topic was addressed. Class I evidence from head-to-head studies provides the best tool for direct comparisons of DMDs. However, other EBM approaches to data analysis from placebo-controlled trials can be used to help determine the benefits and risks of a particular DMID relative to placebo by calculating the number needed to treat to achieve a positive outcome, such as avoiding a relapse, and the number needed to harm to produce an additional adverse event, such as having a therapy-related dropout. This provides a structured basis for comparisons between DMDs," wrote D.S. Goodin and colleagues, University of California.

The researchers concluded: "While such comparisons have their limitations, particularly when drugs with substantially different side-effect profiles are to be compared, they can provide useful information to guide treatment decisions."

Goodin and colleagues published their study in Current Medical Research and Opinion (Integrating an evidence-based assessment of benefit and risk in disease-modifying treatment of multiple sclerosis. Current Medical Research and Opinion, 2007;23(11):2823-2832).

Source: NewsRX Copyright 2008, NewsRx.com (31/01/08)

Early Betaseron(R) (interferon beta-1b) Treatment Delays Multiple Sclerosis

Early treatment with the drug interferon slows the progression of multiple sclerosis (MS) in people with the first symptoms of the disease and reduces impairment, a Swiss study shows.

The study of 468 people found that 37 percent of those who got every-other-day injections of Betaseron(R) (interferon beta-1b) progressed to full-blown MS over three years, compared to 51 percent of those who got inactive injections, according to the report in the Aug. 4 issue of The Lancet.

Betaseron(R) (interferon beta-1b) treatment also reduced the progression of disability by 40 percent, the report said.

Those numbers should help resolve a running debate about interferon treatment for people who experience a first episode of disability that warns of MS, said Dr. Ludwig Kappos, head of the MS-Research Group at University Hospital in Basel.

"Other studies, including the early part of this one, showed that early treatment can delay occurrence of a second episode that allows one to make the diagnosis of multiple sclerosis," Kappos said. "But that the treatment had an impact on remaining ability was not clear. This study shows there is a difference, at least for some people."

MS is a disorder of the central system in which the fatty tissue called myelin that surrounds nerve cells is destroyed. It is thought to be an autoimmune condition, wherein the body attacks its own tissue. Several laboratory-made versions of interferon are commonly used to treat the disease.

To Patricia O'Looney, vice president for biomedical research at the National Multiple Sclerosis Society in New York City, an important aspect of this study is that it measured the progression of the disease precisely, patient by patient, using the well-established expanded disability status scale (EDDS). That scale goes in half-point steps from 0.5, the first sign of the disease, to 9.5, total disability.

"What makes this study different is that it shows delay in progression on the EDDS scale, which other studies have not done," O'Looney said.

The Swiss results "provide more evidence to support the value of early treatment," she said. "There has been disagreement about whether early treatment is beneficial. This provides additional evidence that early treatment delays progression on a disability scale."

An accompanying editorial by Dr. Sean Pittock, a neurologist at the Mayo Clinic, praised the study, saying, "Kappos and colleagues have set a new standard against which future extension trials will be compared."

But Pittock said the results of the trial should be "interpreted with care, because the magnitude of benefit, although significant, is clinically small. This follow-up should not be misconstrued as evidence for a 'treat all' approach."

Kappos said he agreed with that assessment, but he noted that the trial covered only the first few years of a condition that could progress for decades. "In the early stages of the disease, the changes are minor," he said. "Later on, they can cause more severe problems. Changes that may look minor at an early stage take on greater importance."

"Even if it is only marginal, a significant delay is still a delay," O'Looney said. "To someone with MS, even a marginal delay in the loss of the ability to walk is important."

What the study results provide in the decision about treatment of a specific patient is "one more argument why it is important to have this treatment," Kappos said. "Then it is their decision. The treatment can cause side effects, and they have to weigh one against the other."

But the side effects of interferon treatment generally are "benign," Kappos added. The treatment would be especially helpful to patients in whom silent brain lesions are found by MRI scans, he said.

"This is an important argument to be considered by patients," Kappos said, and the trial results have changed the frame of that discussion. "Several years ago, neurologists hesitated to discuss it," he said, referring to early treatment. "Now, they can take the time to discuss it."

Source: Forbes.com © 2007 Forbes.com LLC™   All Rights Reserved (03/08/07)

MS patients not receiving medications to slow disease progression, research shows.

Neurologists at Wake Forest University Baptist Medical Center have found that many patients diagnosed with multiple sclerosis (MS) are not taking or being prescribed drugs approved to treat the disease.

"When we looked at patients who are being seen by family practitioners and by neurologists, we were surprised at the number of people who are not benefiting from drugs proven to help reduce the side effects of MS," said Cormac O'Donovan, M.D., a neurologist and co-investigator of the study. "Hopefully by educating physicians about the benefits of these drugs and beginning treatment early, we can slow the progression of this disease."

O'Donovan's research was published this month by Biomed Central Medicine on their website.

O'Donovan and his team studied patient visits to family practitioners, neurologists or internists between 1998 and 2004 across the United States. There were an estimated 6.7 million MS patient visits to physicians during this time. Neurologists recorded the most patient visits (50.7 percent).

About 62 percent of patients visiting neurologists and 92 percent seen by family practitioners/internists were not using immunomodulatory agents (IMAs), according to the research. Treatment with IMAs is known to reduce the frequency of relapses and slow disease progression.

Six IMAs have been approved by the U.S. Federal Drug Administration (FDA) for use in treating MS. They are: interferon-1b (sold under the name Betaseron® ), interferon-1a (Avonex®), glatiramer acetate (GA or Copaxone®), interferon-1a (Rebif®), mitoxantrone (Novantrone®) and natalizumab (Tysabri®).

"Our study could not determine exactly why these FDA approved drugs were not being prescribed for the treatment of MS," O'Donovan said. "Some individuals may have mild symptoms at first and decide to defer treatment. Other factors may be that physicians are not as familiar with the newer drugs on the market and the risk-to-benefit ratio. Some patients may not even be aware of the pros and cons of IMAs or were advised by their physician that they did not meet the criteria for taking the drug. The increased use of IMAs by neurologists probably reflects greater awareness of the drugs' availability and their use by specialists who more often treat patients with MS. We need to spend some time looking further into the issue."

MS is an inflammatory disease of the central nervous system. It is the second most common cause of neurological disability in young adults. The cause of MS is unknown but environmental factors and genetics are thought to contribute to the onset of the disease.

Data for this research was obtained from surveys conducted annually by the National Center for Health Statistics and the Centers for Disease Control and Prevention.

Researchers on O'Donovan's team included: Fabian Camacho, M.S., Steven Feldman, M.D., both of Wake Forest Baptist; and Jagannadha Avasarala, M.D. of Kansas Neurological Consultants and Steven Roach, M.D. with Ohio State University Medical Center, who were at Wake Forest Baptist at the time of the research.

Source: Wake Forest University Baptist Medical Center (28/04/07)

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