May 25, 2004
The National Multiple Sclerosis Society
On May 25, 2004, Biogen Idec and Elan Corporation announced that they had submitted an application to the U.S. Food and Drug Administration seeking approval of Antegren® (natalizumab) as a treatment for MS.
According to a company press release, the application is based on the first-year data from two ongoing, 2-year trials of Antegren alone (“AFFIRM” study) or Antegren in combination (“SENTINEL” study) with Avonex® (interferon beta-1a) in relapsing-remitting MS. The press release also stated that the companies are not disclosing results at this time to protect the integrity of the ongoing trials, and that they planned to continue the trials until their completion. This is exciting news for the MS community, although this application alone does not signify that the drug is safe or effective in MS.
Antegren is a monoclonal antibody that is given by monthly infusion into a vein. It is designed to interfere with movement of potentially damaging immune cells from the bloodstream, across the “blood-brain barrier,” and into the brain and spinal cord. Antegren blocks this movement by attaching to alpha 4-integrin, a protein on the surface of immune T cells which normally enables them to pass through the blood-brain barrier.
A previous six-month, placebo-controlled trial of Antegren, involving 213 people with relapsing-remitting MS or secondary-progressive MS with relapses, suggested that the drug was well tolerated, reduced the accumulation of new “enhancing” brain lesions detected by MRI, and reduced the number of relapses. David H. Miller, MD (Institute of Neurology, Queen Square, London) and colleagues reported these findings in the the January 2, 2003 issue of The New England Journal of Medicine (2003;348:15-23).
The AFFIRM study of Antegren alone is a placebo-controlled study involving some 900 participants in North America and Europe. The SENTINEL study of Antegren combined with Avonex, or Avonex combined with placebo, involves some 1200 participants. Because the companies have submitted an application halfway through the two-year clinical trials, the one-year data submitted from the trials primarily address whether the drug reduced relapse rates. The full, two-year trials are collecting data on both relapse rates and on any slowing of the progression of disability, as measured with the Expanded Disability Status Scale (EDSS).
The Implications of Application: If the application is accepted, a thorough review by the FDA could take a year or longer from the application date before a decision is made about whether to approve the drug for marketing. During that period, FDA scientists and statisticians will thoroughly scrutinize the clinical trials’ data for safety and efficacy. It is common during the evaluation process for the FDA to ask the applicant for additional data to help the agency make an informed decision about the drug’s safety or effectiveness.
The fact that the companies submitted an application for the FDA’s consideration does not necessarily signify that the drug is safe and beneficial. There are several possible outcomes of the application, and any of the following, or other scenarios, might occur:
The fact that a new drug has been submitted for approval to the FDA, which has a different mechanism of action than previously approved drugs for MS, is exciting news for the MS community. The companies’ pledge to continue the trials to their completion is laudable because of the added scientific and clinical knowledge these trials have the potential to contribute.
Although it may be tempting to suggest that the FDA should speed its
review of Antegren in order to possibly make another drug available to
persons with MS, it is important to keep in mind that the FDA is the public’s
best defense against potentially harmful and/or ineffective treatments.
We trust that the agency will continue its track record of due diligence
while bearing in mind the urgent need for safe, new medications for the
treatment of multiple sclerosis.
Copyright © 2004, The National Multiple Sclerosis Society