Results of the Phase 3 SPI2 Study of MD1003 (high dose Pharmaceutical grade Biotin) in Progressive MS (680)

Objective: To evaluate the efficacy and safety of MD1003 (high dose Pharmaceutical grade Biotin) in patients with progressive forms of multiple sclerosis (MS). Background: An unmet need exists for treating primary or secondary progressive MS (PPMS, SPMS). Biotin is a coenzyme for carboxylases that function in energy metabolism and fatty acid synthesis. In the first controlled trial of MD1003 in progressive MS, MS-SPI, treatment resulted in a significant sustained improvement in disability vs placebo. SPI2 is a phase 3, randomized, double-blind, placebo-controlled study of MD1003 in PPMS and SPMS patients receiving or not receiving concomitant, approved disease modifying therapy (NCT02936037). Design/Methods: SPI2 inclusion required documented, relapse-free, disability progression in EDSS over the 2 years before entry. Patients were randomized (1:1) to receive MD1003 100mg tid or placebo. The primary endpoint was the proportion of patients with improvement: decrease in EDSS (0.5 or 1.0) or improved timed 25-foot walk (T25FW) of ≥20% from baseline to month (M) 12, confirmed at M15. Secondary endpoints were time to 12-week confirmed disability (EDSS) progression up to M27, clinical global impression (CGI/SGI), and mean change in T25FW. Results: Overall, 642 patients were randomized: Europe (n=338), North America (n=290), and Australia (n=14). At the time of submission, baseline demographics and disease characteristics were: mean age 52.7 years; 53.7% female; 64.6% SPMS; overall mean time since diagnosis 12.6 years [PPMS 6.9, SPMS 15.6]; mean time since conversion to SPMS 5.0 years; overall mean EDSS 5.4; overall mean T25FW 11.6 seconds. The last patient last visit will be in November 2019 and database lock will be in early 2020. Final results from primary and secondary efficacy endpoints, as well as an analysis of safety will be presented. Conclusions: Results of the phase 3 SPI2 study of MD1003 in this progressive MS population will be presented. Disclosure: Dr. Cree has received personal compensation from Akili, Alexion, Atara, Biogen, EMD Serono, Novartis, TG Therapeutics.Dr. Cutter has received personal compensation from AMO Pharma, Argenix, Atara Bio-therapeutics, Axon, Biogen, BioLineRx, Bio-therapeutics, Brainstorm Cell Therapeutics, Charleston Laboratories, Inc., Click Therapeutics, Genentech, Genzyme, GW Pharma, Horizon Pharmaceuticals, Klein Buendel Inc., MedDay, MedImmune, Merck, Merck/Pfizer, Neurim, Novartis OPKO Biologics, Orphazyme, Pythagoras, Inc, Reata Pharmaceuticals, Receptos/ Celgene, Sanofi- Aventis, Roche, SciFluor, Somahlution, Teva Pharma-ceuticals, TG Therapeutics, UTHealth Houston Teva NeuroscienceDr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for consulting, scientific advisory boards, or other activities with Alkermes, Actelion, Acorda Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanof. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from Royalties are received for out-licensed monoclonal antibodies through UTHealth from Millipore Corporation.Dr. Freedman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer Healthcare, Biogen Idec, Chugai, Clene Nanomedicine, EMD Serono Canada, Genzyme, Merck Serono, Novartis, F. Hoffmann-La Roche Ltd, Sanofi-Aventis and Teva Canada Innovation. Dr. Freedman has received compensation for serving on the Board of Directors of Actelion, Bayer Healthcare, Biogen Idec, Clene Nanomedicine, F. Hoffmann-La Roche Ltd, Merck Serono, MedDay Pharmaceuticals, Novartis and Sanofi-Aventis. Dr. Freedman has received research support from Genzyme Canada. Dr. Comi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with honoraria for consultancy and/or speaking activities from Almirall, Biogen, Bayer, Chugai, Genzyme, Merck Serono, Novartis, Roche, Receptos, Sanofi, Serono Symposia International Foundation, and Teva.. Dr. Comi has received personal compensation in an editorial capacity for Clinical Investigation; European Journal of Neurology and Multiple Sclerosis; Neurological Sciences. Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB. Dr. Giovannoni has receive research support from AbbVie, Actelion, Atara Biotherapeutics, Bayer, Biogen, Canbex Therapeutics, Five Prime Therapeutics, GSK, GW Pharmaceuticals, Merck, Merck Serono, Novartis, Oxford PharmaGenesis, Protein Discovery Laboratories, Roche, Sanofi Genzyme, Synthon, Teva, and UCB.Dr. Hartung has received personal compensation from Bayer Healthcare, Biogen Idec, CSL Behring, GeNeuro, Genzyme, MedImmune, Merck Serono, Novartis, Opexa, Receptos, Roche, Sanofi, Teva, and Viela Bio.Dr. Sedel has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with MedDay Pharmaceuticals. Dr. Sedel has received compensation for serving on the Board of Directors of MedDay Pharmaceuticals. Dr. Sedel holds stock and/or stock options in MedDay Pharmaceuticals. Dr. Lublin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen; EMD Serono; Novartis; Teva; Actelion; Sanofi/Genzyme; Acorda; Roche/Genentech; MedImmune; Receptos/Celgene; Forward Pharma; TG Therapeutics; Abbvie; Regeneron; Medday; Atara Biotherapeutics; Polpharma; Mapi Pharma; Innate Immunotherapeutics; Apito. Dr. Lublin has received personal compensation in an editorial capacity for Multiple Sclerosis and Related Disorders- Co-Chief Editor. Dr. Lublin has received research support from Acorda Therapeutics, Biogen Idec, Genzyme, National MS Society, Novartis, Sanofi, Teva Neuroscience.