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Phase 3 Trial of Natalizumab Shows 66 Percent Reduction in Relapse Rate in Multiple Sclerosis
The AFFIRM study is a two-year trial evaluating the effect of natalizumab on the progression of disability and the rate of relapses in MS. The primary endpoint of the one-year analysis was relapse rate. The companies anticipate that the two-year results will be available in the first half of 2005.
Adverse events occurring in at least 5 percent of natalizumab-treated patients that were 2 percent more common than in placebo-treated patients included headache, fatigue and arthralgia. The overall incidence of infection was similar between the groups. Serious infections occurred in 1 percent of placebo-treated patients and 2 percent of natalizumab-treated patients. Serious hypersensitivity-like reactions occurred in approximately 1 percent of natalizumab-treated patients.
"These data demonstrate that natalizumab dramatically reduced the rate of relapses at one year," said Burt Adelman, MD, executive vice president, Development, Biogen Idec. "We believe natalizumab, with its novel mechanism of action, has the potential to be a significant step forward in the treatment of MS."
"Natalizumab has the potential to make a real difference in the lives of MS patients," said Lars Ekman, executive vice president and president, Research and Development, Elan. "We are working closely with regulatory authorities to make natalizumab available to patients in need as soon as we can."
The AFFIRM trial is a two-year, randomized, multi-center, placebo-controlled, double-blind study of 942 patients evaluating the effect of natalizumab monotherapy on the progression of disability in MS and the rate of clinical relapses. Secondary endpoints at one year included the number of new or newly enlarging T2-hyperintense lesions, the number of gadolinium-enhancing lesions and the proportion of patients who were relapse free. To enroll, patients had to be diagnosed with a relapsing form of MS and had to have experienced at least one relapse in the previous year. Patients were randomized to receive a 300 mg IV infusion of natalizumab (n=627) or placebo (n=315) once a month.
"This was a rigorous, well-conducted clinical trial across 99 sites worldwide that yielded compelling one-year results," said Chris Polman, MD, PhD, lead investigator of the AFFIRM study, professor of neurology at Free University Medical Centre, and clinical and scientific director of the Multiple Sclerosis Centre at the VU Medical Centre, Amsterdam. "These data suggest that natalizumab may become a promising new treatment option for patients with MS and could help address a significant unmet need."
Biogen Idec and Elan have submitted regulatory applications for the approval of natalizumab as a treatment for MS in the U.S., EU, Canada, and Australia based on one-year data from two ongoing Phase III trials. On May 25, the companies announced that they had submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA). The FDA designated natalizumab for Priority Review and Accelerated Approval. Based on the FDA's designation of Priority Review, the companies anticipate action by the FDA approximately six months from the submission date, rather than 10 months for a standard review. Regulatory authorities in Canada and Australia have also designated natalizumab for Priority Review, and the European Medicines Agency (EMEA) is actively reviewing the application.
A second Phase III trial, SENTINEL, is a two-year randomized, multi-center, placebo-controlled, double-blind study of approximately 1,200 patients with relapsing-remitting MS, evaluating the effect of the combination of natalizumab and AVONEX® (Interferon beta-1a) compared with AVONEX alone on the progression of disability and the rate of clinical relapses.
MS is a chronic disease of the central nervous system that affects approximately 400,000 people in North America and more than one million people worldwide. It is a disease that affects more women than men, with onset typically occurring between 20 and 40 years of age. Symptoms of MS may include vision problems, loss of balance, numbness, difficulty walking and paralysis.
About ANTEGREN (natalizumab)
Natalizumab, a humanized monoclonal antibody, is the first alpha-4 integrin antagonist in the new selective adhesion molecule (SAM) inhibitor class.
It is designed to inhibit the migration of immune cells into tissues where they may cause or maintain inflammation. To date, over 2,800 patients have received natalizumab in clinical trials.
Biogen Idec and Elan are collaborating equally on the development of natalizumab in MS, Crohn's disease (CD), and rheumatoid arthritis (RA). In September 2004, a Marketing Authorisation Application (MAA) for CD was filed with the EMEA based on Phase III studies, and another Phase III induction trial for CD is ongoing. A Phase II trial is also underway to evaluate natalizumab in RA.
Source: Biogen Idec and Elan Corporation