ACE-083 is an experimental therapy developed by Acceleron Pharma to treat muscle-wasting diseases — specifically facioscapulohumeral muscular dystrophy (FSHD) and Charcot-Marie-Tooth disease (CMT).

Due to a lack of efficacy shown in Phase 2 clinical trials, Acceleron halted the development of ACE-083 for FSHD, though the treatment is still being developed for CMT.

How does ACE-083 work?

FSHD is a disease characterized by the progressive weakening of muscles, starting in the face, shoulders, and upper arms.

ACE-083 is designed to increase the strength and function of specific muscles. The therapy contains a small molecule that binds to and inhibits select proteins in the TGF-beta protein superfamily, namely activins and myostatin, which reduce muscle growth.

Normally, muscle size is controlled by a balance of building and breaking down muscle. Exercise helps muscles to grow. If a person stops exercising, the muscles gradually reduce in size, due to the function of activins and myostatin, among other factors.

Inhibiting the TGF-beta family — sometimes called the “myostatin +” approach — reduces or slows muscle breakdown. This approach is thought to increase muscle mass and strength where the treatment is administered. Untreated muscles or other organs are not affected, which reduces the potential of side effects.

ACE-083 in clinical trials

A Phase 1 clinical trial (NCT02257489) evaluated the safety and tolerability of single and multiple doses of ACE-083 administered as a local injection into selected skeletal muscles of healthy volunteers. The study also determined the amount of ACE-083 that reached systemic circulation following local administration, and whether local administration into a skeletal muscle can lead to an increase in muscle size and/or strength.

The results of this trial were presented at the 14th International Congress on Neuromuscular Disease in 2016. They showed that local administration of ACE-083 into the rectus femoris muscle (one of the muscles of the upper leg) was well-tolerated and associated with dose-dependent increases in muscle volume.

A Phase 2 clinical trial (NCT02927080) of ACE-083 in patients with FSHD to evaluate the treatment’s safety, tolerability, pharmacodynamics (effect on the body), efficacy, and pharmacokinetics (movement in the body) was conducted in two parts. The first part enrolled 23 participants, 11 of whom had lower leg weakness and 12 had upper arm weakness. Patients received two doses of ACE-083 — either 150 mg or 200 mg — injected directly in the affected muscles once every three weeks for a treatment period of three months. Preliminary results from the first half of the trial indicated that treatment with ACE-083 could increase patients’ muscle mass.

In the second half of the trial, 56 patients were randomly assigned to receive either ACE-083 or a placebo. Participants received nine doses, administered once every three weeks.

Although muscle mass increased in patients treated with ACE-083, the increase did not lead to improvements in functional muscle tests (such as the six-minute walk test, which is a measure of how far participants can walk in six minutes). As a result, Acceleron decided to end its clinical trials of ACE-083 for FSHD, though the company plans to continue evaluating ACE-83 for CMT.

Other information

The U.S. Food and Drug Administration granted ACE-083 fast track and orphan drug designations for the treatment of FSHD and CMT.

Last updated: Sept. 29, 2019


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