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A New Oral Immunomodulator for MS

Fingolimod showed promising results in a preliminary trial, but safety concerns must be examined further.

This was a phase 2, multicenter, placebo-controlled, manufacturer-funded trial of a new immunomodulatory agent for the treatment of multiple sclerosis (MS). Researchers randomized 281 patients with relapsing MS and Expanded Disability Scale Scores of 0 to 6 to receive fingolimod (either 1.25 mg or 5.0 mg daily) or placebo in a 1:1:1 ratio. The core study lasted 6 months; in a subsequent 6-month extension study, those who received active drug in the core study continued to do so, and placebo recipients were randomized to 1.25 mg or 5.0 mg of fingolimod. The primary endpoint was the total number of gadolinium-enhanced lesions recorded on T1-weighted MRI at monthly intervals for 6 months.

In the core study, the median total number of gadolinium-enhanced lesions on MRI was significantly lower with both 1.25 mg of fingolimod (1 lesion) and 5.0 mg of fingolimod (3 lesions) than with placebo (5 lesions). The annualized relapse rates were also significantly lower in the fingolimod groups than in the placebo group (53% lower with 5.0 mg and 55% lower with 1.25 mg). Adverse events with fingolimod included bradycardia soon after the first dosage, nasopharyngitis, dyspnea, headache, diarrhea, and nausea. One case of the posterior reversible encephalopathy syndrome occurred in the 5.0-mg group. The authors conclude that oral fingolimod provided significant and rapid improvement in MRI measures of inflammation and in relapse-related clinical endpoints.

Comment: If these encouraging results are confirmed in phase 3 of this study (currently underway), they will constitute an important advance in the treatment of MS. Fingolimod would be the first oral medication for MS. The phase 3 trial is expected to proceed with lower doses of fingolimod, as more side effects were seen in this study with the 5.0-mg dose without added benefits.

— Samia Khoury, MD

Dr. Khoury is Associate Professor of Neurology, Harvard Medical School, and Co-Director of the Partners MS Center, Brigham and Women's Hospital, Boston.

Published in Journal Watch Neurology December 5, 2006

Citation(s):

Kappos L et al. for the FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med 2006 Sep 14; 355:1124-40.

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