Acceleron Pharma announced top-line results from a phase 2 trial of ACE-083 for the treatment of facioscapulohumeral muscular dystrophy (FSHD). The trial failed to reach statistically significant improvements in functional secondary endpoints relative to placebo. Based on these results Acceleron is discontinuing the development of ACE-083 for FSHD.
The phase 2 study was conducted in two parts and was designed to evaluate ACE-083 in FSHD patients with muscle weakness in the biceps brachii (BB) and the tibialis anterior (TA), a muscle in the lower leg involved in foot dorsiflexion (raising the foot at the ankle). Part 1 was an open-label, dose-escalation study, with ACE-083 administered by injection into the BB or TA muscle to evaluate safety and increases in muscle volume over a 3-month treatment period. Part 2 was a randomized, double-blind, placebo-controlled study using the optimal dose level selected in Part 1. A total of 56 patients were randomized in Part 2 to receive either placebo or ACE-083 and were evaluated for changes in muscle volume, fat fraction, strength, function, quality of life, and safety over a 6-month primary treatment period, followed by a 6-month open-label treatment period.
Although ACE-083 demonstrated a robust, statistically significant increase in mean total muscle volume, the primary endpoint of the trial, the increase failed to translate to statistically significant improvements in functional tests. Acceleron expects to present results at a future medical meeting.
The FDA has granted ACE-083 Fast Track and Orphan Drug designations. A phase 2 trial is currently underway for Charcot-Marie-Tooth disease.
About Facioscapulohumeral Muscular Dystrophy (FSHD)
Facioscapulohumeral muscular dystrophy is a genetic disorder characterized by muscle weakness and wasting (atrophy). This condition gets its name from the muscles that are affected most often: those of the face (facio-), around the shoulder blades (scapulo-), and in the upper arms (humeral).
ACE-083 is designed to bind to and inhibit select proteins in the TGF-beta protein superfamily that negatively regulate (reduce) muscle growth, such as activins and myostatin (GDF8). This “Myostatin +” approach, is believed to increase muscle mass and strength in the muscle where the drug is administered. Untreated muscles or other organs are not affected, reducing the potential for systemic side effects.