Acceleron Stops Clinical Development of ACE-083 as Treatment for FSHD

Due to a lack of efficacy, Acceleron Pharma is halting the clinical development of its ACE-083 candidate for the treatment of facioscapulohumeral muscular dystrophy (FSHD) .

Topline results from a Phase 2 clinical study showed that ACE-083 was well-tolerated and could significantly increase muscle mass, which was the trial’s main goal. However, the treatment failed to improve muscle function as assessed by multiple different tests, which was the trial’s secondary goal for treating FSHD.

The company will present the trial’s full results in upcoming meetings.

“We are certainly disappointed with these results. As we have stated consistently, for ACE-083 to become an important new therapy for patients with FSHD, it would have to deliver a meaningful functional benefit on top of an ability to grow muscle,” Habib Dable, president and CEO of Acceleron, said in a press release. “Unfortunately, in this case, the data show no evidence of such a benefit and, therefore, do not support further development of ACE-083 for FSHD.”

“We’re grateful to the patients, families, caregivers, and investigators who participated in this research,” he added.

FSHD is characterized by debilitating skeletal muscle weakness and loss. ACE-083 was developed as a locally acting agent to block proteins in the transforming growth factor (TGF)-beta family, such as myostatin, which are responsible for reducing muscle strength and growth.

ACE-083 had received both fast track designation and orphan drug status from the U.S. Food and Drug Administration in 2018 for the treatment of FSHD.

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The safety and effectiveness of the therapy was being evaluated in the two-part Phase 2 clinical trial (NCT02927080) in people with FSHD who had muscle weakness affecting the tibialis anterior and biceps brachii — the calf and bicep muscles.

Weakness in the muscle of the lower leg is the main cause of dorsiflexion — the inability to lift the front of the foot when taking a step — in people with FSHD.

The first part of the study enrolled a total 23 participants, of whom 11 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 showed that ACE-083 could increase patients’ muscle mass.

In the second part of the trial, 56 people were randomly assigned to receive an optimal dose of ACE-083 — defined based on the results of the first part of the study — or a placebo. The participants received a total of nine doses, administrated once every three weeks for approximately six months.

Researchers evaluated the impact of ACE-083 on muscle function using several tests, such as the six-minute walk-distance test and the 4-stair climb test, which determine exercise capacity and endurance.

Although ACE-083 did demonstrate a statistically significant increase in mean total muscle volume, which was the trial’s primary endpoint, that increase failed to translate to statistically significant improvements in functional tests. As a result, Acceleron has decided to stop its clinical trials of ACE-083 in FSHD.

However, the company is still exploring ACE-083 as a potential treatment for Charcot-Marie-Tooth disease, a genetic disorder that affects the function of both arms and legs. A Phase 2 trial (NCT03124459) is testing the therapy for CMT.

“We now look toward the first quarter of next year, when we expect topline results from the placebo-controlled Phase 2 trial of ACE-083 in patients with Charcot-Marie-Tooth disease—a neuromuscular disorder of different pathophysiology,” Dable said.