RARE Daily

Acceleron Stops Development of Charcot-Marie-Tooth Therapy after Reporting Mid-Stage Results

March 10, 2020

Rare Daily Staff

Acceleron Pharma has discontinued development of its experimental therapy for patients with Charcot-Marie-Tooth disease after it reported the drug failed to produce functional improvements in a mid-stage trial.

The drug, ACE-083, did show a statistically significant increase in mean total muscle volume, the trial’s primary endpoint, but the increase did not translate to statistically significant improvements in any of the functional or quality of life secondary endpoints when compared to placebo.

“Unfortunately, over the course of multiple clinical trials, our myostatin-plus hypothesis has not resulted in the functional outcomes necessary to provide clinically meaningful benefits for patients with neuromuscular diseases,” said Habib Dable, president and CEO of Acceleron.

Charcot-Marie-Tooth (CMT) disease is a group of rare inherited disorders that affect the peripheral nerves that run from outside the brain and spine. Defects in at least 30 genes cause different forms of this disease. Common symptoms may include foot drop, foot deformity, loss of lower leg muscle, numbness in the foot or leg, feet hitting the floor hard when walking, and weakness of the hips, legs, or feet. There is currently no cure for Charcot-Marie-Tooth disease, but physical therapy, occupational therapy, braces and other orthopedic devices, pain medication, and orthopedic surgery can help manage and improve symptoms.

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). The first part was an open-label, dose-escalation study, with ACE-083 administered by injection into the TA muscle once every three weeks in 18 patients to evaluate safety and increases in muscle volume over a three-month treatment period.

The second part 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 and largely injection-site related. Acceleron plans to present results of the study at the American Academy of Neurology Annual Meeting in April.

Photo:  Habib Dable, president and CEO of Acceleron

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