The FDA has informed Biogen, Inc. (NASDAQ: BGEN) that Rebif’s labeling does not enable Serono to make a general claim for clinical superiority over AVONEX®, Biogen said today. FDA’s Chief Counsel told Biogen that if Serono makes such broad claims not supported by the labeling he will take enforcement action. The approval letter for Rebif specifically prohibits such claims.
Rebif Approval Based on Limited, Short-Term Benefit
After carefully reviewing the FDA’s decision on Rebif, Biogen said the approval is based on limited findings from a short-term study. As FDA makes clear, “This study was not designed to assess the broad range of actions of Rebif. It was designed to address the requirements of orphan drug regulations to gain early marketing approval.”
“Now that we have studied the approved label, the orphan drug decision and the existing 48-week data from the EVIDENCE trial, it is eminently clear that Rebif was admitted onto the U.S. market because of a small benefit versus AVONEX on relapse rate at 24 weeks that does not persist during the second 24 weeks of the study. Importantly, safety data from this study did not demonstrate a benefit for Rebif,” said Burt Adelman, Biogen’s Executive Vice President for Research and Development.
“Since MS is a life-long disease, the number one goal of MS therapy is to reduce the long-term accumulation of disability. Data describing Rebif clearly show that the short-term effect on relapse rate does not result in an improved long-term impact on disability progression versus AVONEX. In fact, the EVIDENCE study does not support any conclusion regarding effects on the accumulation of physical disability. AVONEX has been shown to slow the accumulation of disability by 37 percent when compared to placebo,” Dr. Adelman continued.
Favorable AVONEX Safety Profile Ignored
The approval decision also did not consider the comparative safety profiles of AVONEX and Rebif. Marlene Haffner, Director of the Office of Orphan Products Development stated, “The difference in adverse events between AVONEX and Rebif is real. For example, the injection-site necrosis observed with Rebif is not observed with AVONEX.” But the Agency decided that an inferior safety profile was not relevant when the exclusivity was being broken based on an efficacy measure.
Leading Neurologists Raise Concerns About Long-Term Rebif Treatment
Leading neurologists also raised concerns about Rebif’s propensity to generate higher rates of neutralizing antibodies — a critical, but sometimes overlooked, difference between MS therapies. Neutralizing antibodies develop during therapy and can block useful drug action and reduce long-term efficacy. The long-term PRISMS study on Rebif documented that “efficacy decreased with neutralizing antibody formation.”
“The incidence of generating neutralizing antibodies is much lower for AVONEX than it is for Rebif,” said Dr. Timothy Vartanian, MD, Ph.D. Dr. Vartanian is Director, MS Treatment Center, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, and Assistant Professor of Neurology at the Harvard Medical School. He indicated that in the EVIDENCE trial, the incidence of neutralizing antibodies was 2 percent for AVONEX and 24 percent for Rebif.
“I don’t think that Rebif is clinically superior to Avonex,” said William H. Stuart, MD, Medical Director of the MS Center of Atlanta. “You have to factor into any drug that you use over ten years the concepts of side effects, of compliance, of neutralizing antibodies, of how the drug is taken.”
Rebif Pricing About 30 Percent Higher Than AVONEX
Serono’s announced pricing for Rebif is about 30 percent higher than AVONEX. During its lengthy efforts to break Biogen’s orphan drug exclusivity, Serono met frequently with legislators and patient groups, positioning itself for entry into the U.S. market as a lower cost alternative.
AVONEX is for the treatment of relapsing forms of multiple sclerosis to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. It is approved to reduce relapses and slow the progression of disability. It is believed that AVONEX works by slowing down the underlying disease process in relapsing forms of MS. AVONEX is taken just once a week because it is an intramuscular (IM) injection. Because AVONEX is injected directly into the muscle, it is released slowly into the bloodstream. IM injections allow effective amounts of AVONEX to stay in the body longer, thus not requiring frequent injections.
The most common side effects associated with AVONEX treatment are flu-like symptoms, muscle ache, fever and chills. AVONEX should be used with caution in people with depression and in 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.
About Biogen, Inc.
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 European sales of AVONEX® (Interferon beta-1a) for treatment of relapsing forms of multiple sclerosis, (Please see full prescribing information at http://www.avonex.com.), 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.
AVONEX® (Interferon beta-1a) is a registered trademark of Biogen, Inc.