January 13, 2003
Pain & Central Nervous System Week
The commercially available dose of Biogen, Inc.'s (BGEN) multiple sclerosis therapy Avonex 30 mcg (interferon beta-1a) 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 (IFNbeta-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." The study was published in the journal Neurology.
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-microg dose was chosen for comparison to the commercially available dose because pharmacodynamic data have suggested that increasing the IFNbeta-1a dose from 30 microg to 60 microg potentially led to a greater level of induction of biological markers (i.e., neopterin and beta2-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 microg or 60 microg 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 1 year and at least 2 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% 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 microg dose was 2.3% (9 of 400 patients) and the neutralizing antibody rate for the 60 microg dose was 5.8% (23 of 395 patients).
The neutralizing antibody rate for the 30 microg 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% (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,
did find higher incidences of some side effects in the individuals
receiving the higher, 60 microg dose."
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