Preliminary Results from a Phase 2 Study to Evaluate ACE-083, a Local Muscle Therapeutic, in Patients with Facioscapulohumeral Muscular Dystrophy (S38.001)

Objective: To evaluate the safety, pharmacodynamics (PD), efficacy, and pharmacokinetics of ACE-083 in patients with facioscapulohumeral muscular dystrophy (FSHD). Background: ACE-083 is a locally-acting therapeutic based on follistatin that binds myostatin and other muscle regulators. It has been shown to increase muscle mass and force in neuromuscular disease mouse models and to increase muscle mass in healthy volunteers. Design/Methods: In this study, Part 1 is dose-escalation, open-label, and Part 2 is placebo-controlled. ACE-083 was injected into either the tibialis anterior (TA) or biceps brachii muscle every 3 weeks for 5 doses. Total muscle volume (TMV) and intramuscular fat fraction (FF) were assessed by MRI (Dixon method) on Days 1, 43, 106, and 141. PD assessments include timed motor function tests, gait analysis, and the FSHD-Health Index. Results: Data were available for this abstract as of Sept 22, 2017 and are shown for patients treated with 150 mg unilaterally into the TA muscle (n=6). Median (range) age was 46.5 yr (42–52), duration of symptoms was 26.5 yr (5–35), and FF was 36.5% (13.6–68.7). Increases in TMV and decreases in FF were seen by Day 43. At Day 106, mean (SD) percent change on the treated side in TMV was 6.7% (8.9) and absolute change in FF (%) was −4.8% (6.4). In the contralateral untreated TA muscle, these changes were −0.5 (7.7) and −0.8 (1.1), respectively. Related adverse events included transient injection site pain/discomfort and myalgia; there were no serious AEs. Dose escalation is ongoing. Conclusions: ACE-083 was well-tolerated in patients with FSHD and encouraging results were seen for changes in muscle volume and fat fraction in the initial dose cohorts. These preliminary results support further studies of ACE-083 in neuromuscular disorders; current ongoing studies include FSHD and Charcot-Marie-Tooth disease. Disclosure: Dr. Statland has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Strongbridge, Acceleron, Regeneron, and Sanofi. Dr. Amato has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Strongbridge Pharmaceuticals. Dr. Bravver has nothing to disclose. Dr. Campbell has nothing to disclose. Dr. Elman has nothing to disclose. Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speakering, or other activities with AMO Pharma, AveXis and Strongbridge Pharma. Dr. Johnson has received compensation in an editorial capacity for Neurology Genetics. Dr. Johnson has received research support from Biogen Idec, Cytokinetics, AMO Pharma, AveXis and Ionis Pharmaceuticals. Dr. Joyce has nothing to disclose. Dr. Karam has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with alnylam, alexion, sanofigenzyme,nufactor, soleohealth, optioncare. Dr. Kissel has received research support from Novartis, Biomarin, Cytokinetics, CSL Behring, Avexis, Ionis Pharmaceuticals, Quintiles, Axelacare. Dr. Korngut has nothing to disclose. Dr. O9Ferrall has nothing to disclose. Dr. Manousakis has nothing to disclose. Dr. Pestronk has nothing to disclose. Dr. Shieh has nothing to disclose. Dr. Tawil has nothing to disclose. Dr. Leneus has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Sherman has nothing to disclose. Dr. Glasser has nothing to disclose. Dr. Attie has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Versartis.