Effect of MD1003 (High Doses of Biotin) in Progressive Multiple Sclerosis: Results of a Pivotal Phase III Randomized Double Blind Placebo Controlled Study (PL2.002)

Abstract

OBJECTIVE: To evaluate the efficacy of Biotin 300 mg/day over placebo in patients with progressive multiple sclerosis (PMS). BACKGROUND: Biotin is a water-soluble vitamin acting as a coenzyme for carboxylases involved in key steps of energy metabolism and fatty acids synthesis. Among others, biotin activates acetylCoA carboxylase, a potentially key-enzyme in myelin synthesis. In one previous open-label pilot study involving 23 patients, it was found that high doses of biotin (100 to 600 mg/day) resulted in progressive and sustained improvement of disability in primary and secondary PMS patients. DESIGN/METHODS: This is a randomized, double-blind, multicenter, placebo-controlled (2:1) trial of oral biotin 300 mg / day in patients with secondary or primary PMS with EDSS between 4.5 and 7 and evidence of EDSS progression within the past two years. Treatment duration was 48 weeks. The primary endpoint was the proportion of patients who improved at M9 and confirmed at M12, defined as decreased EDSS (by at least 1 point for EDSS ≤5.5 and .5 point for EDSS 蠅6) or improved TW25 of at least 20[percnt]. Other endpoints included MSWS, CGI, [percnt] patients with stable or worsened EDSS, SF36, FIS, 9HPT. RESULTS: The last patient is scheduled to complete the study January 2015. Baseline characteristics: 154 subjects from 16 sites across France were randomized; mean age 51.4; mean disease duration 16.6 years; 41[percnt] had PPMS and 59[percnt] had SPMS. The mean EDSS score was 6.1. The database will be locked by March 2015. Detailed results from primary and other outcomes will be presented. CONCLUSIONS: This trial will evaluate the efficacy of Biotin 300 mg/d in a randomized, placebo-controlled trial. Effects of treatment with high doses of biotin in patients with PMS will be discussed in the context of future development of high doses of biotin as a novel potential treatment in PMS.

Disclosure: Dr. Tourbah has received personal compensation for activities with Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, and Teva Neuroscience. Dr. Lebrun has received personal compensation for activities with Bayer Pharmaceuticals Corporation, Biogen Idec, Merck Serono, Genazyme, Almirall, Allergan, Inc., Novartis and Sanofi as a speaker. Dr. Edan has received personal compensation for activities with LFB, Biogenidec, speaking from Serono, Inc., Sanofi, Teva, and Bayer Pharmaceuticals Corporation as a consultant and/or scientific advisory board member. Dr. Clanet has received personal compensation for activities with Teva, Merck Serono, Genzyme, and Biogen Idec as a consultant and/or scientific advisory board member. Dr. Papeix has received personal compensation for activities with Teva Neuroscience, Novartis, Laboratoires Servier, and Roche Diagnostics Corporation. Dr. Vukusic has received personal compensation for activities with Bayer Schering Pharma, Biogen Idec, Genzyme Corporation, Novartis, Merck Serono, Sanofi-Aventis Pharmaceuticals, Inc., and Teva Neuroscience. Dr. De Seze has nothing to disclose. Dr. Debouverie has received personal compensation for activities with Biogen Idec, Bayer Schering, Merck Serono, Novartis, Sanofi-Aventis, and Teva Neuroscience. Dr. Gout has received personal compensation for activities with Allergan, Inc., Almirall, Bayer-Schering, Biogen Idec, Genzyme, Novartis, Merck Serono, Sanofi, and Teva. Dr. Clavelou has received personal compensation for activities with Biogen Idec, Teva Pharmaceutical Industries, Almirall, Novartis, Merck Serono, Bayer, and Genzyme. Dr. Defer has received personal compensation for activities with Genzyme, Teva, Merck. Dr. Laplaud has received personal compensation for activities with Novartis, Biogen Idec, Teva Neuroscience, and Genzyme as a speaker and/or advisory board participant. Dr. Moreau has received personal compensation for activities with Biogen Idec, Sanofi-Aventis Pharmaceuticals, Genzyme, Teva Neuroscience, Bayer Schering, Merck Serono, Novartis, and Almirall. Dr. Labauge has nothing to disclose. Dr. Brochet has received personal compensation for activities with Bayer HealthCare, Novartis, Merck Serono, Biogen Idec, Genzyme, and Teva. Dr. Sedel has received personal compensation for activities with Actelion Pharmaceuticals and MedDay Pharmaceuticals. Dr. PELLETIER has nothing to disclose.