Positive Phase 2 CMT Trial Results of Acceleron’s ACE-083 Presented at Meeting

Acceleron’s therapy candidate ACE-083 was seen to improve total and contractile muscle volume in patients with Charcot-Marie-Tooth (CMT) disease in preliminary results from a Phase 2 trial. The study is still recruiting patients.

The positive data was presented by Acceleron at this year’s Annual Meeting of the Peripheral Nerve Society, July 22-25 in Baltimore, Maryland.

The results appeared in both a poster and an oral presentation titled “Preliminary Phase 2 Results for ACE-083, Local Muscle Therapeutic in Patients with CMT1 and CMTX.“

“Preliminary Phase 2 results of ACE-083 in patients with CMT show robust mean increases in total and contractile muscle volume, reductions in fat fraction, and an encouraging safety profile,” Robert K. Zeldin, MD, chief medical officer of Acceleron, said in a press release.

ACE-083 is a locally-acting drug designed to increase muscle strength and function at target muscles. It is based on the naturally-occurring protein follistatin, and works by inhibiting a group of proteins belonging to the TGF-β family of proteins that reduce muscle growth.

Because the drug is injected directly into target muscles, untreated muscles or other organs are not affected, reducing the chances of side effects.

Acceleron is developing ACE-083 for people with disorders such as CMT and facioscapulohumeral muscular dystrophy (FSHD), to whom more muscle strength may represent a clinical benefit and a better quality of life.

A Phase 1 trial (NCT02257489) showed that the therapy was well tolerated and led to increased target muscle growth in healthy volunteers.

The positive results warranted advancement into a Phase 2 trial (NCT03124459) to evaluate the safety, tolerability, bioavailability, and effectiveness of ACE-083 in patients with CMT type 1 and CMT type X.

The trial has two parts, a Part 1 that is a nonrandomized, open-label, dose-escalation study, and a Part 2 that is a randomized, double-blind, placebo-controlled study, primarily to evaluate efficacy.

Part 1 enrolled a total of 18 patients with CMT1 or CMTX, divided in three separate cohorts, each injected with an increasing dose of ACE-083.

Patients were injected into one of the major muscles of the lower leg called the tibialis anterior, the primary muscle allows the front of the foot to lift when taking a step. Patients were treated once every three weeks for three months.

Three weeks after the last injection, magnetic resonance imaging (MRI) revealed the muscle volume had increased from 12.6% to 14.2% compared to baseline values before treatment.

Such improvement in muscle volume was accompanied by a decrease in the proportion of fat in the muscles.

Treatment with ACE-083 also improved the volume of contractile muscle from 15.8% to 19.6%, meaning the therapy candidate was able to increase the growth of viable and functional muscle.

Overall, the treatment showed a favorable safety profile. The most common adverse events were mild or moderate and included injection-site reactions, muscle spasms, and pain.

“We now look forward to initiating the randomized, placebo-controlled portion of the Phase 2 trial in which we will evaluate ACE-083’s potential to improve function over a six-month treatment period.” Zeldin said.

Part 2 of the Phase 2 trial is expected to enroll approximately 40 patients with CMT1 or CMTX. Patients will be randomly assigned to receive either placebo or ACE-083 once every three weeks over a six-month double-blind treatment, followed by an open-label treatment period, also of six months.

Throughout the study, patients will be monitored for changes in muscle volume, fat fraction, strength, function, and adverse events.

The study is currently recruiting and preliminary results of the second part of the study are expected by the end of 2019. For more information about the Phase 2 trial, visit the official trial website here.