Data published in the November 26, 2002 issue of the journal Neurology determine that the commercially available dose of Biogen, Inc.´s (NASDAQ: BGEN) multiple sclerosis therapy AVONEX 30 mcg once weekly is equally as effective in treating patients with relapsing-remitting multiple sclerosis as a higher dose of 60 mcg once weekly.
“For many years, neurologists have been debating what the optimal dose of Interferon beta-1a (IFNb-1a) is and whether a higher dose may be more effective in treating patients with relapsing forms of MS,” said Alfred W. Sandrock, MD, PhD, Biogen´s Senior Director of Medical Research and co-author of the study. “This study shows that a 60 mcg dose of AVONEX is not more effective than a 30 mcg IM once weekly dose of AVONEX.”
This study “provides clear, high-quality evidence that the higher dosage of this preparation given on a once-weekly basis confers no therapeutic advantage,” said Karl Kieburtz, MD, and Michael McDermott, PhD, both of the Department of Neurology, University of Rochester Medical Center, in an independent editorial in the same issue of Neurology. “This type of study is of great utility to clinicians and patients in avoiding the unnecessary use of higher dosages, which may be associated with higher long-term toxicity and higher costs.”
The objective of the study was to determine whether a higher dose of AVONEX, 60 mcg IM once weekly, is clinically more effective than AVONEX 30 mcg IM once weekly in reducing disability progression in relapsing-remitting MS. The 60-mcg dose was chosen for comparison
to the commercially available dose because pharmacodynamic data have suggested that increasing the IFNb-1a dose from 30 mcg to 60 mcg potentially led to a greater level of induction of biological markers (i.e., neopterin and b2-microglobulin), without a notable increase in side effects.
The randomized, double-blind, parallel-group, dose-comparison study was conducted at 38 centers in Europe. Over 800 participants with varying levels of disability participated.
Patients were randomized to receive AVONEX 30 mcg or 60 mcg IM once weekly for at least 36 months. Subjects were included in the study if they had a definite diagnosis of relapsing MS for at least one year and at least two medically documented relapses within the 3 years prior to randomization.
The primary endpoint was disability progression, defined as time to a sustained increase on the Expanded Disability Status Scale (EDSS). Both groups showed equal rates of disability progression. The rate of disability progression after 36 months was 37 percent in both the 30 mcg and 60 mcg groups. Additional endpoints included relapses, MRI, safety, and subgroup analyses of disability progression. No significant differences were observed among any of these endpoints.
Regarding antigenicity in this study, the data continue to demonstrate the low neutralizing antibody rate for AVONEX. In this trial, the neutralizing antibody rate for the 30 mcg dose was 2.3% (9 of 400 patients) and the neutralizing antibody rate for the 60 mcg dose was 5.8% (23 of 395 patients). The neutralizing antibody rate for the 30 mcg dose is consistent with a recent U.S. Food and Drug Administration approved label change. This label change was based on recent studies with multiple sclerosis patients given AVONEX for at least 1 year, which showed the presence of neutralizing antibodies at the rate of 5 percent (13 of 261 patients). The clinical significance of neutralizing antibodies to AVONEX is unknown.
“According to the results of this study, there is no clinical benefit for people with relapsing-remitting MS to take a higher dose of AVONEX,” said Professor Michel Clanet, University of Toulouse, and chief investigator of the European Avonex Dose Comparison Study. “Both doses were equally effective and generally well-tolerated. However, we did find higher incidences of some side effects in the individuals receiving the higher, 60 mcg dose.”
About AVONEX® (Interferon beta-1a)
AVONEX is the leading treatment for relapsing forms of multiple sclerosis worldwide, with more than 120,000 patients on therapy. It was launched in the U.S. in 1996 and later in Europe for the treatment of relapsing forms of MS to slow the progression of disability and reduce relapses. AVONEX is marketed internationally in more than 65 countries.
The most common side effects associated with AVONEX treatment are flu-like symptoms, muscle ache, fever, and chills. Other common side effects seen, but not statistically different between AVONEX and control groups, were headache, pain and asthenia (weakness). These side effects usually go away within a day after the injection and occur less often as the treatment continues.
AVONEX should be used with caution in people with depression and people with seizure disorders. AVONEX should not be used by pregnant women. People with cardiac disease should be closely monitored. Routine periodic blood chemistry and hematology tests are recommended during treatment with AVONEX. Please see complete prescribing information available at www.AVONEX.com .
Biogen, Inc., winner of the U.S. National Medal of Technology, is a biotechnology company principally engaged in discovering and developing drugs for human healthcare through genetic engineering. Headquartered in Cambridge, MA, the Company´s revenues are generated from U.S. and worldwide sales of AVONEX® (Interferon beta-1a) for treatment of relapsing forms of multiple sclerosis, and from the worldwide sales by licensees of a number of products, including alpha interferon and hepatitis B vaccines and diagnostic products. Biogen´s research and development activities are focused on novel products to treat inflammatory and autoimmune diseases, neurological diseases, cancer, fibrosis and congestive heart failure. The Company maintains active clinical research programs in protein therapeutics, small molecules, genomics and gene therapy. For copies of press releases and additional information about the Company, please consult Biogen´s Homepage on the World Wide Web at http://www.Biogen.com.
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