Tysabri Studies Suggest MS Efficacy May More than Balance PML Risk : A GOOD OVERVIEW OF THE THREE ARTICLES IN THE NEJM...CLICK HERE TO READ

"Review
AMSTERDAM, March 1 - Although the promising multiple sclerosis drug Tysabri (natalizumab) was pulled from the market in 2005 for safety concerns, an initiative to bring it back from limbo gained support from three studies released today.

The three studies were published in the March 2 issue of the New England Journal of Medicine. They followed by two weeks a move by the FDA to allow resumption of clinical trials for Tysabri for patients with MS who were previously treated with the drug.

Considered a major advance for MS treatment, the drug was approved for marketing by the FDA in late 2004 but was withdrawn three months later in light of the first two cases of progressive multifocal leukoencephalopathy (PML), two of them fatal. Biogen-IDEC and Elan suspended trials a year ago.

The FDA has scheduled an advisory committee meeting next week to discuss an application for Tysabri for use in treating patients with relapsing forms of multiple sclerosis.

In one study in the NEJM, a multinational randomized trial comparing Tysabri with placebo for relapsing MS found that the drug reduced the clinical relapse rate and the risk of sustained progression of disability compared with placebo. Patients taking Tysabri had 92% fewer MS lesions on MRI than controls, reported Chris H. Polman, M.D., of Vrije University Medical Center here and colleagues in the AFFIRM study group.

In a second study, Tysabri in combination with Avonex (interferon beta-1a) was significantly more effective than Avonex alone at preventing relapses over two years, reported Richard A. Rudick, M.D., of the Cleveland Clinic and colleagues in the SENTINEL trial.

In this study, however, two of 589 patients on Tysabri developed PML and one died of the progressive and often fatal demyelinating disease.

But a third study reviewing records of more than 3,100 patients who received Tysabri in clinical trials found no new cases of PML beyond the three that had already been reported. The estimated risk for PML was about one in 1,000 patients treated with Tysabri for a mean of 17.9 months, wrote Eugene O. Major Ph.D., of the National Institute of Neurological Disorders and Stroke in Bethesda, Md., and colleagues in the United States and Europe.

The studies "extend the efficacy of the drug to the two-year mark and provide reassurance that the risk of PML is small with relatively brief use," wrote Allan H. Ropper, M.D., a neurologist at Caritas St. Elizabeth's Medical Center in Boston, in an accompanying editorial.

"Beyond these findings, clinicians and patients are left wondering if and when natalizumab will be made available and what precautions might be taken to prevent the emergence of the JC virus, the causative agent of PML," Dr. Ropper added.

The JC virus is a polyomavirus believed to be latent in about 80% of adults....[MORE]"