CMT AND NEUROGENIC DISEASE: P.339Preliminary phase 2 results for ACE-083, local muscle therapeutic, in patients with CMT1 and CMTX

Abstract

ACE-083 is a locally acting muscle 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. Charcot-Marie-Tooth (CMT) disease is a hereditary neuropathy characterized by lower leg weakness leading to foot drop and increased risk of falls. This ongoing multicenter, Phase 2 study evaluates the safety, tolerability, pharmacodynamics, efficacy, and pharmacokinetics of ACE-083 in patients (pts) with CMT1 and CMTX with mild-moderate weakness in ankle dorsiflexion. In this two-part study, ACE-083 is administered bilaterally into the tibialis anterior (TA) muscle q 3 weeks. Part 1 is 3-month, open-label with 3 dose-escalating cohorts (6 pts per cohort); Part 2 is 6-month, randomized, double-blind, placebo-controlled (followed by 6-month open-label), and will enroll an additional 40 pts. The primary objective of Part 1 is safety and tolerability; the objectives for Part 2 include muscle volume, strength, function, and quality of life. Data as of 31 Jan 2018 are available for Part 1 Cohort 1 (n=6) treated with 150 mg/muscle and are presented as the average of left and right TA muscles. Median (range) age was 35 yrs (23-62) with 3 male/3 female. Four pts had CMT1A, 1 had CMT1B, and 1 had CMTX. Median (range) duration of symptoms was 31 yrs (14-61) and mean (SEM) baseline fat fraction (FF) was 28.4% (5.8). No serious AEs have been reported and related AEs were primarily injection-site related and all grades 1-2. Preliminary data show mean (SEM) percent change in total muscle volume from baseline to Day 106 (3 weeks after last dose) of 12.6% (2.9). Mean (SEM) change in FF from baseline to Day 106 was -1.7% (1.2). In summary, local muscle injections of ACE-083 were well tolerated in pts with CMT and resulted in marked increases in muscle volume. Data from all 3 cohorts in Part 1 will be presented at the meeting.