Phase 2 BOLD Extension Study Efficacy Results for Siponimod (BAF312) in Patients with Relapsing–Remitting Multiple Sclerosis (P07.110)

OBJECTIVE: To explore siponimod (BAF312) efficacy in patients with relapsing–remitting multiple sclerosis during the first 12 months of an extension to the BOLD study. BACKGROUND: In the adaptive dose-ranging, 6- or 3-month BOLD study, once-daily siponimod versus placebo showed dose-dependent reduction of combined unique active lesion number and annualized relapse rate (ARR); near-maximal effects were observed at 2mg. Here, we report the first 12 months of the extension (representing > 18 or 15 months of total treatment). DESIGN/METHODS: Patients either continued on siponimod doses assigned in the core phase or were re-randomized from placebo to siponimod 10, 2, 1.25, 0.5 and 0.25mg: 33, 29, 43, 29 and 50 patients comprised each dose group, respectively. Patients had >7 days (washout time) study drug interruption between core and extension phases to enable siponimod dose titration from 0.25mg over the first 10 days. Magnetic resonance imaging (MRI) was performed at extension baseline, month 6 and month 12. RESULTS: 263/297 (88.6%) patients completed the core study; 184 of these (62.0%) entered the extension. The following data pertain to patients taking 10, 2, 1.25, 0.5 and 0.25mg, respectively. 27, 25, 37, 24 and 37 patients had a 12-month MRI, and mean gadolinium-enhancing lesion numbers at extension month 12 were: 0.1, 0.5, 0.1, 0.6, 0.8 (compared with 1.7, 1.4, 1.8, 3.1, 1.3 at core study baseline, and 1.7 in placebo at month 6). Mean numbers of new/enlarged T2 lesions at extension month 12 were 0.4, 0.6, 0.2, 1.7 and 1.7, and ARRs were 0.27 (95% confidence interval, 0.14–0.52), 0.18 (0.08–0.42), 0.13 (0.06–0.28), 0.34 (0.18–0.64) and 0.33 (0.20–0.54). No new safety issues were observed. CONCLUSIONS: Over the 12-month extension, MRI-assessed inflammatory lesion activity and ARRs remained low, particularly in the 1.25, 2 and 10mg treatment groups, with no new safety concerns. Supported by: Novartis Pharma AG. Disclosure: Dr. Hartung has received personal compensation for activities with Biogen Idec, Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Inc., Bayer, Novartis, and Merck Serono. Dr. Freedman has received personal compensation for activities with Bayer, Biogen Idec, Teva, Merck Serono, Novartis, Sanofi, and Celgene. Dr. Freedman9s institution has received research support from Bayer Healthcare and Genzyme. Dr. Li has received personal compensation for activities with Genzyme, Novartis, and Nuron as a consultant. Dr. Li has receved research support from Angiotech, Bayer, Berlex-Schering, Bio-MS, Boehringer-Ingelheim, Centocor, Daiichi Sankyo, Genentech, Hoffmann-LaRoche, Merck-Serono, Perceptives, Schering-Plough, Teva Neurosciences, and Sanofi-Aventis. Dr. Hemmer has received personal compensation for activities with Roche, Novartis, Bayer, GlaxoSmithKline, Inc., Chugai, Genzyme Corporation, Biogen Idec, Merck Serono, and Teva Neuroscience. Dr. Hemmer has received personal compensation in an editorial capacity for Archives of Neurology. Dr. Hemmer has filed a patent for KIR4.1 antibody testing. Dr. Hemmer has received research support from Biogen Idec, Bayer Schering, Merck Serono, Metanomics and Novartis. Dr. Kappos has receied personal compensation for activities with Actelion, Advancell, Allozyne, BaroFold, Bayer Health Care Pharmaceuticals, Bayer Schering Pharma, Bayhill, Biogen Idec, BioMarin, CLC Behring, Elan, Genmab, Genmark, GeNeuro SA and GlaxoSmithKline. Dr. Kappos has received research support from has received research support from Acorda, Actelion, Allozyne, BaroFold, Bayer HealthCare, Bayer Schering, Bayhill Therapeutics, Biogen Idec, Boehringer Ingelheim, Eisai, Elan, Genmab, GlaxoSmithKline, Glenmark, Merck Serono, MediciNova and Nova. Dr. Stuve has received personal compensation for activities Teva Neuroscience, Biogen Idec, Roche, Genzyme, Novartis and sanofi-aventis. Dr. Stuve has received personal compensation in an editorial capacity for Archives of Neurology and Therapeutic Advances in Neurological Disorders. Dr. Stuve holds stock in Teva Pharmaceuticals which sponsored research in which Dr. Stuve was involved as an investigator. Dr. Stuve has received research support from Teva Pharmaceuticals. Dr. Rieckmann has received personal compensation for activities with Bayer, Biogen Idec, Boehringer Ingelheim, Novartis, Merck-Serono, Teva and Genzyme as a speaker. Dr. Montalban has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, EMD Serono, Genentech, Genzyme, Novartis, and Sanofi-Aventis. Dr. Ziemssen has received personal compensation for activities with Almirall, Biogen Idec, Bayer Pharmaceuticals Corporation, Genzyme Corporation, GlaxoSmithKline, Merck Sharp & Dohme Limited, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc., Teva Neuroscience, Synthon as a consultant. Dr. Ziemssen has received research support from Biogen Idec, Bayer Pharmaceuticals Corporation, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals, Inc. and Teva Neuroscience. Dr. Zhang-Auberson has received personal compensation for activities with Novartis Pharma AG as an employee. Dr. Hunter has received personal compensation for activities with Novartis as an employee. Dr. Rochotte has received personal compensation for activities with Novartis Pharma AG as an employee. Mr. Wallstrom has received personal compensation for activities with Novartis Pharma AG as an employee. Mr. Wallstrom holds stock and/or stock options in Novartis Pharma AG. Dr. Selmaj has received personal compensation for activities with Biogen Idec, Genzyme, Ono Pharmaceutical, Novartis, Bayer, Hoffmann LaRoche, Merck, Serono and Synthon.