Phase 1 Trial of Acceleron’s CMT Therapy ACE-083 Shows Positive Results in Healthy People

ACE-083, an investigative therapy for the treatment of Charcot-Marie-Tooth (CMT) disease, was well tolerated and resulted in increased targeted muscle growth in healthy volunteers in a Phase 1 clinical trial, results show.

The study, “Locally Acting ACE-083 Increases Muscle Volume in Healthy Volunteers,” was published in the journal Muscle & Nerve.

Acceleron‘s ACE-083 is a locally-acting drug that binds to a protein called myostatin and other muscle regulators, and works by increasing the growth of muscles. One of the benefits of ACE-083 is that it acts in a targeted manner in muscles where it is administered.

ACE-083 has also been shown to increase muscle mass and strength in mice with neuromuscular disease.

Researchers conducted a Phase 1 randomized, placebo-controlled trial (NCT02257489) to test single and multiple doses of ACE-083 as a local injection into selected skeletal muscles of healthy postmenopausal women ages 45-75.

Researchers tested three single doses — 50 mg, 100 mg, and 200 mg — and multiple doses of 100 mg, 150 mg, and 200 mg doses.

The study’s primary objective — its endpoint — was to assess the therapy’s safety and tolerability. Additional, or secondary, endpoints tested its effectiveness by measuring muscle strength and volume compared to placebo.

Participants received a range of 50-200 mg ACE-083 or placebo that was administered into either the rectus femoris — a muscle in the middle of the front of the thigh, or the tibialis anterior, which is a muscle located primarily near the shin. Participants received either 1 or two doses three weeks apart.

Among the 58 women enrolled, 42 received ACE-083 and 16 received placebo.

Safety results showed that there were no serious adverse events, dose-limiting toxicities, or discontinuations due to adverse events.

The maximum mean increase in muscle volume for the rectus femoris muscle was 14.5%, and 8.9% for the tibialis anterior muscle. However, researchers failed to detect significant changes in mean muscle strength.

“These unprecedented increases in total muscle volume produced in the Phase 1 trial of ACE-083 were critical in leading us to rapidly advance into two Phase 2 trials in two distinct diseases of focal muscle weakness,” Matthew Sherman, MD, chief medical officer of Acceleron, said in a press release.

ACE-083 is now being tested in two Phase 2 clinical trials — one for CMT (NCT03124459), currently enrolling participants, and one for facioscapulohumeral dystrophy (FSHD).

Preliminary results from Part 1 of the FSHD trial showed there was a mean muscle total volume increase of over 12 percent in patients who received ACE-083 in the tibialis anterior and biceps brachii — both muscles in the upper arm.

The final results from Part 1 of both Phase 2 trials are expected in the second half of 2018. Part 2 of the FSHD trial is expected to begin soon, with results expected in 2019. Part 2 of the CMT trial is expected to begin by the end of 2018.

“We believe ACE-083 could have a significant impact in increasing muscle mass, strength, and function in patients with neuromuscular disorders,” Sherman said.