Acceleron Pharma announced that the Phase II clinical trial of ACE-083 in patients with Charcot-Marie-Tooth disease (CMT) failed to show functional improvement. The company indicated the drug did show a statistically significant increase in mean total muscle volume, which was the primary endpoint of the trial. However, ACE-083 didn’t lead to statistically significant improvements in function or quality of life secondary endpoints. Based on these results, Acceleron will discontinue development of the drug.
The two-part Phase 2 clinical trial was designed to evaluate ACE-083 in CMT patients with muscle weakness in the tibialis anterior (TA), a muscle in the lower leg involved in ankle dorsiflexion (raising the foot at the ankle). Part 1 was an open-label, dose-escalation study, with ACE-083 administered by injection into the TA muscle once every 3 weeks in 18 patients 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 44 patients were randomized and treated with either placebo or ACE-083 in Part 2 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.
ACE-083 was generally well tolerated. Adverse events were mostly mild to moderate (Grade 1 or 2) and largely injection-site related. Acceleron plans to present results of the study at the American Academy of Neurology Annual Meeting in April.
ACE-083 is a locally acting therapeutic candidate based on the naturally-occurring protein follistatin, utilizes the Myostatin+ approach to inhibit multiple TGF-beta superfamily ligands. It is designed to have a concentrated effect along targeted muscles to maximize growth and strength selectively in the muscles into which the drug is administered.
Charcot-Marie-Tooth (CMT) is one of the most common inherited neurologic diseases, estimated to affect more than 125,000 people in the United States. The primary clinical manifestations of CMT include muscle weakness in the lower legs and hands. The lower leg muscle weakness can result in foot drop leading to frequent trips and falls. The disease is typically diagnosed by a characteristic pattern of muscle weakness and sensory deficits, family history, nerve conduction studies, and genetic testing. There are no approved therapies for CMT.