Long-Term (7-Year) Data from a Phase 2 Extension Study of Fingolimod in Relapsing Multiple Sclerosis (P01.129)

Abstract

Objective: To report long-term outcomes and safety of fingolimod in relapsing multiple sclerosis (RMS) patients participating in a phase 2 study. Background After the 6-month (M) placebo controlled study in which fingolimod (1.25mg and 5mg dose groups) significantly reduced MRI and relapse activity compared to placebo all patients were invited to continue on fingolimod. The final analysis after 7 years is presented. Design/Methods: In the extension, placebo patients were re-randomized to fingolimod 1.25mg or 5mg (placebo/fingolimod group); fingolimod patients (1.25 or 5mg) continued with their core phase dose (fingolimod group). After the M24 visit, all patients received open-label, 1.25mg fingolimod and between M24-M60 were converted to 0.5mg. Results: Of 281 initially randomized patients 122 (43.4%) completed up to 7 years on study (core and extension). The overall ARR for the fingolimod group was 0.16 and for placebo/fingolimod 0.21. By study completion, 55-66% of fingolimod and 44% of placebo/fingolimod patients were relapse-free. The KM estimate of the proportion of patients who were free from 6-month confirmed disability progression ranged from 53-70% for both groups. At the end of study, 83% of all remaining patients were free of gadolinium-enhanced lesions. No increase in T2 lesion volume was observed. No chronic effects of fingolimod treatment were observed on heart rate or atrioventricular conduction. No cases of confirmed macular edema were observed. Twelve cases of skin malignancies have been reported (majority within the first 3 years): 5, basal cell carcinoma; 4, squamous cell carcinoma; 3, malignant melanoma. Conclusions: Long-term (>7 years) fingolimod treatment was associated with sustained low MRI and clinical disease activity in those remaining on therapy and was well tolerated with no new safety concerns arising with long-term dosing. Supported by: Novartis Pharma AG, Basel, Switzerland. Disclosure: Dr. Antel has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc., Biogen Idec, Novartis, Serono, Inc., Genzyme Corporation, Teva Neuroscience, and GlaxoSmithKline. Dr. Antel has received personal compensation in an editorial capacity for Multiple Sclerosis. Dr. Antel has received research support from Novartis. Dr. Montalban has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals, Almirall and BTG. Dr. Montalban has received research support from Bayer Schering Pharma, Biogen Idec, EMD Merck Serono, Genentech, Genzyme, Novartis, sanofi-aventis, Teva Pharmaceuticals, Almirall and BTG. Dr. O9Connor has received personal compensation for activities with Abbott Labratories, Inc., Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceuticals Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals as a consultant. Dr. O9Connor has received research support from Abbott Labratories, Bayer Pharmaceuticals Corporation, Biogen Idec, BioMS, Cognosci, Daiichi Pharmaceutical Corporation, Serono, Inc., Genentech, Inc., Genmab, Novartis, Roche Diagnostics Corporation, Sanofi-Aventis Pharmaceuticals, Teva Neuroscience, Warburg Pincus and Wyeth Pharmaceuticals. Dr. De Vera has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Cremer has received personal compensation for activities with Novartis. Dr. Sfikas has received personal compensation for activities with Novartis as an employee. Dr. Comi has received personal compensation for activities with Novartis, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Merck Serono, Bayer Schering, and Biogen Dompe. Dr. Kappos has received research support from Acorda Therapeutics, Actelion, Allozyne, BaroFold, Inc., Bayer Pharmaceuticals Corporation, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim Pharmaceuticals, Inc, Elan Corporation, Genmab, GlaxoSmithKline, Inc., Glenmark Pharma, Merck Serono, MediciNova, Novartis, Sanofi-Aventis Pharmaceuticals, Santhera Pharmaceuticals, Shire, Roche Diagnostics, Teva Neuroscience, UCB Pharma, Pfizer Inc, Swiss MS Society, Swiss National Research Foundation, European Union, Gianni Rubatto Foundation, Novartis and Roche Research Foundations.