Emma Hitt, PhD

June 07, 2011

June 7, 2011 (Lisbon, Portugal) — New data from 2 studies help confirm the benefits of fingolimod (Gilenya, Novartis) in patients with relapsing multiple sclerosis (MS), including reductions in annualized relapse rates and the risk for 3-month confirmed disability progression, as well as efficacy, in patients with persistent disease activity.

Fingolimod was approved by the US Food and Drug Administration (FDA) September 2010 and is a first-in-class sphingosine-1 phosphate receptor modulator approved for treating MS. It is considered the first oral disease-modifying drug to reduce relapses and delay disability progression in patients with relapsing forms of MS.

Approval was based on pivotal phase 3 studies, FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS) and Trial Assessing injectable interferoN vS FTY702 Oral in RrMS (TRANSFORMS), both published in the February 4, 2010, issue of the New England Journal of Medicine and previously reported by Medscape Medical News.

In an oral session at the 21st Meeting of the European Neurological Society here, Eva Havrdova, MD, with the Department of Neurology, at the Charles University in Prague, Czech Republic, presented the findings of a subgroup analysis from the 2-year FREEDOMS study.

In the FREEDOMS phase 3 study, 1272 patients with relapsing-remitting MS were randomized to once-daily fingolimod, 0.5-mg or 1.25-mg capsules, or matching placebo for up to 2 years.

A total of 1033 patients (81%) remained in the study at 2 years. Fingolimod reduced annualized relapse rates compared with placebo: patients with mild disability (n = 1060) showed a 52% relative reduction with the 0.5-mg dose and a 66% reduction with the 1.25-mg dose compared with placebo (P < .001).

In patients with moderate to severe disability, the annualized relapse rates were 66% and 54% for the 2 doses, respectively (P < .001).

Fingolimod was also associated with a reduction in disability progression, and the risk of disability progression was similar in previously treated and treatment-naive patients.


In a second presentation, an analysis of data from the TRANSFORMS study, the benefits of fingolimod were also demonstrated in MS patients experiencing persistent disease activity despite previous treatment. Jeffrey Cohen, MD, with the Cleveland Clinic Foundation, in Ohio, led the study.

In TRANSFORMS, patients were randomized to receive either fingolimod, 0.5 mg or 1.25 mg once daily, or a weekly intramuscular interferon beta-1a, 30 ìg for 12 months. For the 12-month extension part of the study, patients taking fingolimod continued with the same dose or were switched from interferon beta-1a and were further randomized to receive either fingolimod at a dose of 0.5 or 1.25 mg.

Fingolimod was effective in reducing disease activity in the subgroup of patients with persistent disease activity (1 relapse in the previous year and at least 1 gadolinium-enhancing lesion at the time of assessment at the baseline) and who had received at least 1 disease-modifying therapy (interferon, glatiramer acetate, or natalizumab) in the year before the study.

At the beginning of the study, active disease was present in a similar proportion, about one-fourth to one-third of patients, regardless of treatment group. After 1 year, active disease persisted in less than 2% of patients receiving fingolimod, compared with 12.1% (21/173) of patients receiving interferon beta-1a.

In the extension study, active disease remained infrequent in patients treated with fingolimod for a second year (0.5 mg: 2.0%; 1.25 mg: 1.5%). In patients who were switched from interferon beta-1a to fingolimod, 0.5 mg, the proportion of patients with active disease decreased from 13.7% to 3.0%.

"These findings provide additional confirmation that fingolimod is more effective than interferon beta-1a in patients that had continued activity previously on prior disease therapies," Dr. Cohen told Medscape Medical News.

He added that it is "anticipated that a sizable proportion of patients starting fingolimod therapy in practice will have been treated previously. For some, the reason for switching causes continued activity — these findings support the potential utility of switching.

"The previous treatment in most of these patients was interferon or glatiramer acetate," he said. "However, there are few data concerning safety and efficacy in switching from natalizumab to fingolimod."

Confirming Data

"These studies provide confirming data as to the generalizability of the original clinical trials," said commentator Fred D Lublin, MD, with the Corinne Goldsmith Dickinson Center for MS Mount Sinai School of Medicine, New York City.

"Along with the apparent continued therapeutic effect in the extension phase, these results provide the clinician with more data to assist in choosing therapies for their MS patients," he told Medscape Medical News.

Both studies were supported by Novartis Pharma AG. Prof. Havrdova has served on scientific advisory boards for Biogen Idec, Merck-Serono, Novartis Pharmaceuticals, and Teva; received compensation for travel/honoraria from Bayer, Biogen Idec, Genzyme, Merck-Serono, Sanofi-Aventis, and Teva; and received research funding/grants from Biogen Idec, GlaxoSmithKline, Merck-Serono, Novartis, and Teva. Dr. Cohen reports receiving consulting fees from Biogen Idec, Novartis, EMD Serono, and Teva, lecture fees from Sanofi-Aventis and Waterfront Media, and research support from Genzyme, Novartis, and Teva. Dr. Lublin noted that his sources of funding for research include Acorda Therapeutics Inc, Biogen Idec, Novartis Pharmaceuticals Corp, Teva Neuroscience Inc, Genzyme, Sanofi- Aventis, National Institutes of Health, and National MS Society. Dr. Lublin has consulting agreements/advisory boards/data safety monitoring board relationships with Bayer HealthCare Pharmaceuticals, Biogen Idec, EMD Serono Inc, Novartis, Pfizer, Teva Neuroscience, Genmab, Medicinova, Actelion, Allozyne, Sanofi-Aventis, Acorda, Questcor, Avanir, Roche, Celgene, Abbott, MorphoSys, and Johnson & Johnson.

21st Meeting of the European Neurological Society (ENS): Abstracts O209, P901, and P902. Presented May 29 and 31, 2011.


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