Long-Term Efficacy and Safety of Fingolimod (FTY720) in Relapsing-Remitting Multiple Sclerosis (RRMS): Results from the Extension of the Phase III FREEDOMS Study (S41.004)

Objective: To report long-term efficacy and safety of fingolimod in RRMS, from the phase III FREEDOMS study extension. Background RRMS patients randomized to oral, once-daily(o.d), fingolimod (0.5mg or 1.25mg) in the 2-year, double-blind, FREEDOMS core study, demonstrated a significant improvement in clinical and MRI endpoints versus placebo (PBO)-treated patients. We present here end of study (EOS) results from the extension phase of upto 4 years treatment. Design/Methods: In the extension, patients either continued on the core phase dose (continuous-fingolimod), or were re-randomized (1:1) from placebo to fingolimod (1.25 or 0.5mg/o.d) (PBO-fingolimod). All patients received open-label 0.5mg following a decision to discontinue the fingolimod 1.25mg/day treatment arm from all MS studies. Results: 1033/1272 (81.2%) patients enrolled in FREEDOMS completed the 24M core, and 773/920 (84%) patients enrolled in the extension (60.7% of initially randomized) completed the study. Common reasons for discontinuations were withdrawal of consent (7.2%) and adverse events (AE) (3.4%). Annualized relapse rates (ARR) decreased in the switch/PBO-fingolimod group during the extension phase (PBO-1.25mg, 0.22; PBO- 0.5mg, 0.19) versus the core (ARR= 0.4; p Conclusions: Patients who switched from placebo to fingolimod showed significant improvements in clinical and MRI outcomes (including brain atrophy). Continuous fingolimod treatment was associated with sustained low clinical and MRI disease activity and was well-tolerated. Supported by: Novartis Pharma AG, Basel, Switzerland. Disclosure: 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. Dr. Radue has received personal compensation for activities with AIM, Biogen Idec, and Novartis as a consultant.Dr. Radue has received research support from Actelion, Bayer Schering, Biogen Idec, Merck Serono, and Novartis. 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. Polman has received personal compensation for activities with Biogen Idec, Schering AG, Teva Neuroscience, EMD Serono, Novartis, GlaxoSmithKline, Inc., UCB Pharma, AstraZeneca Pharmaceuticals, Roche Diagnostics and Antisense Therapeutics as a consultant or speaker.Dr. Polman has received research support from Biogen Idec, Schering AG, GlaxoSmithKline, Inc., Novartis, EMD Serono and Teva Neuroscience. Dr. Hohlfeld has received personal compensation for activities with Schering AG, Merck-Serono, Biogen Idec, Teva Neuroscience, Boehringer Ingelheim Pharmaceuticals, Inc.,Novartis, Sanofi-Aventis Pharmaceuticals, Inc. as a consultant and/or speaker. Dr. Hohlfeld has received personal compensation in an editorial capacity for International MS Journal.Dr. Hohlfeld has received research support from Schering AG, Merck-Serono, Biogen Idec, Teva Neuroscience, Norvartis. Dr. Calabresi has received personal compensation for activities with Teva, Biogen Idec, Novartis, Genzyme, Johnson & Johnson, and Vertex. Dr. Calabresi has received research support from Biogen Idec, Teva, EMD Serono, Vertex, Genentech, Abbott, and Bayer. Dr. Selmaj has received personal compensation for activities with Genzyme, Ono, and Biogen Idec. Dr. Agoropoulou has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Jin has received personal compensation for activities with Novartis Pharma AG. Dr. Zhang-Auberson has received personal compensation for activities with Novartis as an employee. Dr. Francis has received personal compensation for activities with Novartis as an employee. Dr. Francis holds stock and/or stock options in Novartis, which sponsored research in which Dr. Francis was involved as an investigator.