Update of FORTITUDE-ALS: A Phase 2, Double-blind, Randomized, Placebo-Controlled, Study to Evaluate Efficacy, Safety and Tolerability of Reldesemtiv in Patients with Amyotrophic Lateral Sclerosis (S5.002)

Objective: To evaluate the tolerability and preliminary efficacy of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS). Background: Reldesemtiv (CK-2127107), is a selective small molecule fast skeletal muscle troponin activator that sensitizes the sarcomere to Ca2+ by slowing Ca2+ release from troponin. Reldesemtiv increased the force generated by the tibialis anterior muscle versus placebo in response to nerve stimulation in healthy volunteers and has potential in the treatment of ALS. Derived from a different chemical scaffold and designed to limit crossing of the blood-brain barrier, it is expected to have fewer central nervous system adverse effects than tirasemtiv, a molecule with similar though less potent effects on fast skeletal muscle. Design/Methods: Key inclusion criteria for FORTITUDE-ALS (Functional Outcomes in a Randomized Trial of Investigational Treatment with CK-2127107 to Understand Decline in Endpoints – in ALS) include diagnosis within 24 months and upright slow vital capacity (SVC) ≥60% of predicted. Participants are randomized 1:1:1:1 to placebo or reldesemtiv at 150 mg twice daily (BID), 300 mg BID, or 450 mg BID for 12 weeks. The primary endpoint is change from baseline in SVC at 12 weeks. Exploratory home-based outcomes (voice analysis and SVC) are also included. Safety and pharmacokinetic endpoints are included, as well as quantitative strength testing using hand held dynamometry and the ALS Functional Rating Scale-Revised. FORTITUDE-ALS is being conducted in the USA, Canada, Australia, Ireland, Spain, and the Netherlands. Results: FORTITUDE-ALS is currently ongoing but is expected to complete enrollment in November 2018. Complete demographic information as well as top line efficacy and safety results will be presented. Conclusions: Efficacy and tolerability data from FORTITUDE-ALS will be presented at the 71st Annual Meeting of the AAN. The results of this study will determine whether phase 3 studies of this compound should be conducted in ALS. Disclosure: Dr. Shefner has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Biogen, Biohaven, Pharnext, and Neuraltus. Dr. Shefner has received personal compensation in an editorial capacity from UpToDate. Dr. Shefner has received research support from Cytokinetics, Amylyx, Biogen, Biohaven, Neuraltus, BIotie, Orphazyme, and Orrion. . Dr. Andrews has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics and Biohaven. Dr. Andrews has received research support from Neuraltus, Roche. Dr. Genge has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AB Sciences, AL-S Pharma, Avexis, Biogen, Cytokinetics, MTPA, and Roche. Dr. Genge has received research support from Sanofi-Genzyme. Dr. Jackson has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Mitsubishi Tanabe Pharma America, Avanir, Strongbridge,CSL Behring, ITF Pharma, Cytokinetics, and Mitsubishi Tanabe Pharma America. Dr. Jackson has received research support from Cytokinetics, NIH, Amylyx, Brainstorm, Mallinckrodt, and Anelixis. Dr. Lechtzin has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Hill-Rom, and Vertex Pharmaceuticals. Dr. Lechtzin has received research support from Vertex Pharmaceuticals and Astra Zeneca. Dr. Miller has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, and Cytokinetics. Dr. Miller has received royalty, license fees, or contractual rights payments from C2N . Dr. Miller has received research support from Biogen and Ionis Pharmaceuticals. . Dr. Cockroft has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics. Dr. Malik has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Inc. Dr. Wei has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics. Dr. Wolff has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Inc. Dr. Wolff holds stock and/or stock options in Cytokinetics, Inc, which sponsored research in which Dr. Wolff was involved as an investigator. Dr. Wolff has received research support from Cytokinetics, Inc. Dr. Rudnicki has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics. Dr. Rudnicki has received compensation for serving on the Board of Directors of Cytokinetics. . Dr. Rudnicki holds stock and/or stock options in Cytokinetics , which sponsored research in which Dr. Rudnicki was involved as an investigator.