Multiple Sclerosis Society
comments on Tysabri trial
The National Multiple Sclerosis Society reported Biogen Idec and Elan Corp. announced the successful completion of a two-year clinical trial of Tysabri® (natalizumab, formerly known as Antegren) in relapsing forms of Multiple Sclerosis (MS). According to a company press release, the two-year trial achieved its primary outcome by slowing the risk of progression of disability by 42%.
The release confirmed the drug reduced the rate of clinical relapses by 67% over two years, and continued to reduce the development of new or newly-enlarging MRI-detected brain lesions, findings consistent with the previously released results of the first year of the trial. Progression of disability was measured using the EDSS (Expanded Disability Status Score), which measures walking ability and other neurologic function.
The companies announced details of the two-year AFFIRM results were to be presented at the American Academy of Neurology meeting, and the two-year data will be submitted to regulatory agencies.
Common side effects included headache, fatigue, urinary tract infection, depression, lower respiratory tract infection, limb and joint pain, and sore throat. The overall incidence of infection was similar between those on Tysabri and those on placebo. Serious infections, such as pneumonia and urinary tract infection, occurred in 3.2% of participants on therapy and in 2.6% on inactive placebo. Tysabri has been associated with hypersensitivity reactions, including serious systemic reactions that occurred at an incidence of less than 1% of patients in the trial.
Longer-term safety information is not available.
The trial was placebo-controlled and involved 942 global participants. In November 2004, the U.S. Food and Drug Administration approved Tysabri for relapsing forms of MS based on first-year results of the AFFIRM trial and of a second trial, “SENTINEL,” which adds Tysabri to Avonex® (interferon beta-1a) therapy. The companies expect results from the SENTINEL trial by mid year.
Unlike other drugs that have already been approved for treating MS, Tysabri is a monoclonal antibody given by infusion into a vein every four weeks. It’s 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. Tysabri inhibits this movement by attaching to alpha 4-integrin, a protein on the surface of immune T cells that normally enables them to pass through the blood-brain barrier. This approach was studied initially in animal models, including studies supported by the National MS Society, which showed that monoclonal antibodies could block such immune cell movement and ameliorate disease.
Commentary: The fact that Tysabri has been shown to be safe and effective over two years against both relapses and progression is excellent news for persons with MS. The National MS Society looks forward to reviewing the full data when they become available.
Further information: Individuals with MS are encouraged to consult their neurologists. In addition, Biogen Idec and Elan have a toll-free number where individuals can call (1-800-456-2255).