Swiss Court Issues Injunction Prohibiting Serono From Misleading Publicity on “EVIDENCE” Study
Biogen, Inc. (NASDAQ/BGEN) today said that Serono continues to make misleading claims of superior efficacy in comparison to Biogen’s multiple sclerosis (MS) drug, AVONEX® (Interferon beta-1a), the world’s leading treatment for the disease. Biogen also said that the Serono announcement adds nothing new in advancing the understanding of the progression of the disease. These data presented are based on a study that lacks scientific rigor and presents an incomplete measure of a serious disease that must be treated over the long-term.
Yesterday a court in Geneva, Switzerland, the worldwide headquarters of Serono, issued an injunction forbidding Serono’s continued misleading presentation of their data related to the “EVIDENCE” study. That court determined that Serono’s claims about relapses and brain lesions are misleading, and specified that criminal penalties could apply to further violations.
Serono has touted dramatic numbers (“a 90 percent greater odds of remaining relapse-free”) instead of reporting what are actually very small numeric differences. The actual differential is less than 12 percentage points: 74.9% of patients on Rebif® were relapse free and 63.3% of patents on AVONEX were relapse free. It is crucial to recognize that the validity of relapse-related statistics is seriously compromised by Serono’s short-term “snapshot” approach that accentuates random relapses unrelated to treatment effects.
The FDA previously rejected Serono’s application for marketing approval in the U.S. In response to ongoing attempts to gain approval, the FDA has maintained its position that the Rebif® data fail to demonstrate clinical superiority to AVONEX®.
“We can only hope that neither individuals with MS, nor their physicians will be misled by these data released to further commercial, rather than scientific, goals,” said Burt Adelman, M.D., Biogen’s Vice President of Medical Research. “We are confident in the FDA’s high scientific standards and the Agency’s ability to carefully evaluate clinical data to assure that the purpose and incentives of the Orphan Drug Act are fulfilled.”
“Serono’s comparative trial is an open-label, short-term marketing-oriented effort that we believe will not survive the rigors of scientific scrutiny,” Dr. Adelman continued. “Serono has focused on comparing only one aspect of MS over an extremely short period of time in a disease that has a complex, multi-faceted course of progression that happens over a long period of time,” he said.
Biogen noted that well-designed Phase III clinical trials conducted over the past eight years do not support Serono’s new claims about Rebif. Moreover, Biogen’s AVONEX has clearly demonstrated its efficacy in slowing the progression of disability and in reducing the frequency of relapses. Biogen said data that differ dramatically from the well-established body of evidence must be seriously questioned.
“There is a wealth of data from well-designed clinical trials that define the risks and benefits of MS products. Serono’s recently announced data do not change this perspective. Specifically, AVONEX has been demonstrated to slow the progression of disability in relapsing MS. Slowing the progression of disability is the more meaningful measurement of this long-term chronic disease. If Serono wanted a scientifically sound comparative trial, rather than a marketing study, they would have selected this more meaningful endpoint of disability progression. They did not,” Dr. Adelman said.
The Serono study design is flawed for the following reasons:
Treating neurologists, nurses, and patients involved in the study were not blinded to treatment. The lack of blinding biased the results in favor of Rebif.
Although the examining neurologists did not receive specific information about each patient’s treatment, blinding would be virtually impossible, due to different modes of administration of the drug and the presence of injection site reactions.
The study’s primary endpoint measures only relapses, rather than measuring sustained progression of disability. This is problematic since the main goal of therapy in MS is to slow the progression of the disease, and patients who are not experiencing relapses may nonetheless be accumulating disability.
The 24-week duration is far too short for a chronic disease. The current body of evidence of the treatments for MS is based on long-term, two-to-three year rigorous clinical trials. Furthermore, because of the development of neutralizing antibodies with interferon beta, long-term treatment trials are essential.
Biogen also referred to new information just released on physicians’ attitudes about clinical trials. According to a new Harris Interactive poll of more than 250 neurologists who treat MS, only a very small portion of respondents (12 percent) believes that less than 12 months is a sufficient length of time for an MS study. In terms of possible outcome measures, the vast majority of surveyed neurologists consider “sustained disability progression” (80 percent) to be a more significant measure of the disease than the number of relapses which patients experienced (20 percent).
Dr. Adelman said, “Our focus at Biogen is to continue to significantly advance the efficacy of treatment for people with MS. Newer therapies are needed with innovative scientific approaches to treat this devastating disease. The work we are doing to develop ANTEGREN® (natalizumab), in collaboration with Elan Pharmaceuticals, is an example of this new direction to offer more solutions to a broader range of MS patients than are currently available. ANTEGREN is a monoclonal antibody with a new mechanism of action that will be entering Phase III clinical trials in the fall.”
AVONEX® is the most prescribed treatment for MS worldwide. It was launched in the U.S. in 1996 and later in Europe for the treatment of relapsing forms of MS to slow the accumulation of physical disability and to decrease the frequency of clinical exacerbations. More than 100,000 patients worldwide are now on AVONEX therapy, which 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 woman. People with cardiac disease should be closely monitored. Routine periodic blood chemistry and hematology tests are recommended during treatment with AVONEX.
In addition to historical information, this press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Reference is made in particular to statements regarding speculation on the likely
view of Serono’s data by the FDA and the implications for the marketplace, as well as statements regarding the anticipated commencement date of Phase III clinical trials of ANTEGREN. These statements are based on the Company’s current beliefs and expectations as to such future outcomes.
Factors which could cause actual results to differ materially from the Company’s current expectations include, with respect to the statements regarding the Serono data, the risk that submitted or longer-term data may be different than announced data, or that the FDA may apply its standards differently than expected and, with respect to the statements regarding ANTEGREN®, the risk that unexpected delays may arise as well as in each case the other risks and uncertainties described from-time-to-time in the Company’s periodic reports filed with the Securities and Exchange Commission.
Biogen, Inc., winner of the U.S. National Medal of Technology, is a biopharmaceutical
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 international 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 ( Prescribing Information ). 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) and ANTEGREN® (natalizumab) are registered trademarks of Biogen, Inc. Rebif® (Interferon beta-1a) is the registered trademark of Serono.