Safety and Tolerability of Dexpramipexole for the Treatment of ALS: Results from the Randomized, Double-Blind, Placebo-Controlled Trial, EMPOWER (PL02.003)

OBJECTIVE: To evaluate the safety and tolerability of dexpramipexole in a phase III study of individuals with amyotrophic lateral sclerosis (ALS), the EMPOWER trial. BACKGROUND: Dexpramipexole was generally well tolerated for up to 9 months in a Phase II trial of ALS. DESIGN/METHODS: EMPOWER is a double-blind, placebo-controlled, international study of dexpramipexole in individuals with familial/sporadic ALS. Participants (18-80 yrs.) with symptom onset ≤24 months before randomization, slow vital capacity ≥65% of predicted, and no history of, or current neutropenia were included. Participants were randomized (1:1) to dexpramipexole 150 mg or placebo twice daily for 12 to 18 months. Randomization was stratified by investigational site, onset site, and riluzole usage. Participants on a stable dose of riluzole for ≥60 days before study start and those not taking riluzole were eligible. Safety and tolerability are being evaluated by monitoring adverse events, physical examination, vital signs, ECG and laboratory evaluations throughout the study. An Independent Data Monitoring Committee (IDMC) meets periodically to assess safety findings. RESULTS: After a rapid enrollment of participants into the study, 943 participants were randomized in EMPOWER. The IDMC has reviewed and approved the safety findings. Final study visits are expected to be completed by the end of October 2012. EMPOWER safety/tolerability results will be presented at the AAN meeting. CONCLUSIONS: This large Phase III study will provide important information on the safety and tolerability profile of dexpramipexole in individuals with ALS. Supported by: Biogen Idec, Inc. Disclosure: Dr. Van den Berg has received personal compensation for activities with Baxter, Biogen Idec and Cytokinetics as a consultant and/or participant on an advisory board. Dr. Cudkowicz has received personal compensation for activities with GlaxoSmithKline, Inc. and Teva Neuroscience. Dr. Cudkowicz has received research support from Biogen Idec and Neuraltis. Dr. Shefner has received personal compensation for activities with Biogen-Idec and Glaxo SmithKline as a member of the advisory boards, and from Cytokinetics, Inc as a consultant. Dr. Shefner has received personal compensation in an editorial capacity for the Neuromuscular Section Editor of UpToDate. Dr. Shefner has received research funding from NIH, the ALS Association, the ALS Therapy Alliance, MDA, Glaxo Smith Kline, Isis Pharmaceuticals, Biogen-Idec, Cytokinetics, Inc., and Sanofi Pharmaceuticals. Dr. Mitsumoto has received personal compensation for activities with Avanir, Knopp, Biogen Idec., Cytokinetics, Sanofi-Aventis, and Shionogi. Dr. Mitsumoto has received research support from Avanir, Knopp, Biogen Idec., Cytokinetics, Sanofi-Aventis, and Shionogi. Dr. Mora has received personal compensation for activities with Biogen Idec. Dr. Ludolph has received consulting fees and travel support from Biogen Idec and TEVA. Dr. Ludolph has received consulting fees from Lundbeck, Knopp Pharmaceuticals, GlaxoSmithKline and Boehringer Ingelheim, as a speaker and honorarium from Biogen, and Merz Pharmaceuticals. Dr. Hardiman has received personal compensation for activities with Ono Pharmaceutical, Sanofi-Aventis Pharmaceuticals, Inc., Biogen Idec, Merck Serono, and Schering. Dr. Hardiman has received personal compensation in an editorial capacity for the ALS Journal. Dr. Ingersoll has received personal compensation for activities with Knopp Biosciences LLC as an employee. Dr. Ingersoll holds stock and/or stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Ingersoll was involved as an investigator. Dr. Archibald has received personal compensation for activities with Knopp Biosciences LLC has an employee. Dr. Archibald holds stock and/or stock options in Knopp Biosciences LLC, which sponsored research in which Dr. Archibald was involved as an investigator. Dr. Li has received personal compensation for activities with Biogen Idec as an employee. Dr. Dong has received personal compensation for activities with Biogen Idec as an employee. Dr. Kerr has received personal compensation for activities with Biogen Idec as an employee and holds stock options in Biogen. Dr. Farwell has received personal compensation for activities with Biogen Idec as an employee.