MADRID—Fingolimod (FTY720), a once-daily capsule, kept 77% of patients with multiple sclerosis (MS) free of relapse for two years in a randomized, placebo-controlled, phase II trial; it is now being tested in two large phase III studies. The new drug produced impressive reductions in the number of lesions detected on MRI and in clinical disease activity in patients with relapsing MS, according to data reported at the 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and in the September 14 New England Journal of Medicine by Ludwig Kappos, MD, and colleagues for the FTY720 D2201 Study Group. Dr. Kappos is a member of the Departments of Neurology and Research at the University Hospital, Basel, Switzerland.

The phase II researchers randomized 281 patients to fingolimod at 1.25 mg/day (n = 93) or 5.0 mg/day (n = 92) or to placebo (n = 92). All patients had a diagnosis of relapsing MS and either two or more relapses during the previous two years, one or more relapses in the year before enrollment, or one or more gadolinium-enhanced lesions detected on MRI at screening. The first six months of the study were double-blinded and placebo-controlled. This was followed by a six-month extension during which patients and investigators were unaware of treatment assignments. Patients who had received fingolimod during the initial six months continued at the same dose in the extension; those who had received placebo were randomly assigned to either 1.25 or 5.0 mg of fingolimod for the extension.

The primary end point was total gadolinium-enhanced lesions recorded on T1-weighted MRI each month for the first six months. Clinical end points included the number of patients remaining free of relapse, the annualized relapse rate, and the time to first relapse.

FEWER LESIONS, REDUCED RELAPSE

"For the 227 patients who completed the extension study, the number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod, and both measures decreased in patients who switched from placebo to fingolimod," the investigators said.

Second-year data showed that the treatment efficacy was largely sustained over this period. The annualized relapse rate was 0.2, up to 77% of patients remained relapse-free, and more than 80% of patients were free from lesions showing active inflammation on MRI.

Although efficacy was not significantly different between the two dosing levels of fingolimod, the higher dose was associated with more adverse events. The most frequent of these were nasopharyngitis and dyspnea, headache, diarrhea, and nausea. One patient developed posterior reversible encephalopathy syndrome after 10 weeks of treatment, of which the investigators commented, "the pathogenesis of this syndrome is unclear but seems to be related to impaired autoregulation and endothelial function."

PHASE II AND BEYOND

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