ACE-083 is a locally-acting protein therapeutic consisting of a modified form of human follistatin that binds myostatin plus other negative regulators of muscle. ACE-083 has been shown to increase muscle mass and force in neuromuscular disease mouse models and to increase muscle mass in healthy volunteers and patients with facioscapulohumeral dystrophy (FSHD).

To evaluate the effects of ACE-083 injected into the tibialis anterior (TA) muscle of patients with CMT1 or CMTX and mild-moderate ankle dorsiflexion weakness. 

This ongoing, multicenter study evaluates safety and tolerability (Part 1); pharmacokinetics, pharmacodynamics, and efficacy (Part 2), of ACE-083 administered bilaterally into the TA every 3 weeks. Part 1 is 3-month, open-label with 3 dose cohorts (150, 200, 240 mg/muscle, n=6 each); Part 2 is 6-month, placebo-controlled, followed by 6-month open-label (n=40 planned). 

As of 24Aug2018, preliminary Part 1 data are: median (range) age 48 yrs (18-62); 11 patients with CMT1A, 4 with CMT1B, and 3 with CMTX1; median (range) baseline fat fraction (FF) 30% (9-45). No serious AEs were reported and related AEs were primarily injection-site related. Changes in MRI parameters across the 3 cohorts are provided at Day 106 (3 weeks after last dose, average left and right sides). Mean percent increase in total muscle volume was 12.6 to 14.2% and contractile muscle volume increased 15.8 to 19.6%. Mean absolute decrease in FF% was -1.7 to -3.5%.

Local muscle injections of ACE-083 were well tolerated in patients with CMT and resulted in increases in muscle volume and decreases in fat fraction. The ongoing, placebo-controlled Part 2 of the study will evaluate effects on function and quality of life.