Oral fingolimod demonstrates reduced MS activity at end of 1- and 2-year treatment periods

Fingolimid, an investigational oral agent, significantly reduces disease activity and the number of relapses among patients with relapsing multiple sclerosis (MS), according to phase 2 results presented at the 131st Annual Meeting of the American Neurological Association in Chicago, Ill.

The sphingosine 1-phosphate receptor modulator fingolimod demonstrated efficacy during a 6-month main trial and maintained low disease activity and lower relapse rates throughout an additional 18 months of extension trials. "The data show that fingolimod may offer important clinical benefits. In addition, it is given conveniently in the form of a once-daily pill," said Ludwig Kappos, MD, Neurology-Neurosurgery, University Hospital, Basel, Switzerland. Treatments currently available for relapsing MS require frequent injections, he said.

A blinded, 6-month extension trial was then conducted, and patients assigned to placebo in the core trial were randomized to receive 1 of the fingolimod doses. Of the 250 patients entering the extension, 227 completed it. Dr Kappos said that the median number of gadolinium-enhanced lesions and relapse rates remained low in the groups that received continuous fingolimod treatment and were reduced among those who had switched from placebo to active treatment.

The most frequent adverse events reported were dose-dependent upper respiratory tract infection (nasopharyngitis), dyspnea, headache, diarrhea, and nausea. An initial dose-dependent decrease in heart rate and a modest reduction in forced expiratory air flow occurred among patients taking fingolimod, as well as an average 5-mmHg increase in systolic blood pressure. Asymptomatic elevations of alanine aminotransferase levels were observed in 10% to 12% of fingolimod patients compared with 1% of placebo patients. There was 1 case of posterior reversible encephalopathy syndrome in a patient receiving fingolimod 5.0 mg.

The full first-year results of the trial were recently published in the New England Journal of Medicine (2006;355:1124–1140).

TWO-YEAR RESULTS

Patients were followed through an additional 12 months of treatment with 1 of the 2 fingolimod dosages and, after a total of 2 years, 87% of those continuously taking the 5-mg dose and 81% of those continuously taking the 1.25-mg dose were free of gadolinium-enhanced lesions, and 74% and 72%, respectively, experienced no relapses. One relapse occurred during the 2 years in 15% of both treatment groups, and 5% of patients in the high-dose group and 7% of patients in the 1.25-mg dose group experienced >2 relapses.

Among patients initially randomized to placebo, 91% of those switched to fingolimod 5 mg and 79% of those switched to fingolimod 1.25 mg remained free of enhanced lesions in the 12 months after the 6-month extension study. No relapses occurred in 24% of both treatment groups. One relapse occurred in 17% of the high-dose patients and 9% of the low-dose patients; 2% and 7%, respectively, experienced >2 relapses during follow-up.

The annualized relapse rate continued to decline during the extension, Dr Kappos said. Patients continuously taking fingolimod 1.25 mg had an annualized relapse rate of 0.20 after 24 months, and those continuously taking the 5-mg dose had a 0.22 annualized relapse rate. Annualized relapse rates for crossover patients were 0.38 in the 1.25-mg group and 0.28 in the 5-mg group after 24 months.

The mean Expanded Disability Status Scale values remained stable in all treatment groups, with 17% and 25% of patients administered continuous fingolimod and 19% and 26% of patients in the crossover groups meeting the established criteria for disability progression.

Dr Kappos said that no new adverse events emerged during the extension phase and that at 24 months, elevations in alanine aminotransferase levels >3 times the upper limit of normal occurred in 15% and 16% of the continuous fingolimod groups and 12% and 15% of the placebo crossover groups. No additional increase in systolic blood pressure was observed, with an average increase from baseline of 4 mmHg after 24 months' treatment.

"The results are promising and, if confirmed by phase 3 data, fingolimod could contribute significantly to improving the quality of life of patients with relapsing MS," Dr Kappos said. Phase 3 trials using fingolimod 1.25 mg are under way, and investigation of a 0.5-mg dose is being planned.

SOURCE Kappos L, O'Connor P, Antel J, et al. Oral FTY720 (fingolimod) in relapsing MS: Results of the dose-blinded extension of a placebo-controlled phase II study [abstract]. Presented at: 131st Annual Meeting of the American Neurological Association; October 8–11, 2006; Chicago, Ill. Abstract M4.