ACE-083 Receives Fast Track Designation for Charcot-Marie-Tooth Disease


Part 2 of the phase 2 trial in CMT is ongoing, expected to enroll 40 patients with the condition.

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The FDA has granted a Fast Track designation to investigational therapy ACE-083, a possible treatment for Charcot-Marie-Tooth (CMT) disease, according to the therapy’s manufacturer, Acceleron Pharma.1

The locally-acting “myostatin+” muscle agent, as the company refers to it, inhibits multiple TGF-beta superfamily ligands, designed to have a concentrated effect along the targeted muscles into which it is administered.

“We’re pleased that the FDA has granted this designation for ACE-083,” Robert K. Zeldin, MD, the chief medical officer of Acceleron, said in a statement. “Patients with CMT currently have no approved therapies. To date, results from our Phase 2 trials have shown that patients treated with ACE-083 experience robust increases in muscle volume. If our ongoing clinical studies show that ACE-083 also improves functional outcomes and confirm the favorable safety profile observed thus far, the Fast Track process could help us work with the FDA to deliver it to patients as quickly as possible.”

In a phase 1 trial in healthy volunteers, the treatment showed that the therapy was well tolerated, with no serious adverse events, dose-limiting toxicities, or discontinuations attributable to adverse events (AEs). Additionally, a maximum mean increase in muscle volume for the rectus femoris muscle was 14.5%, and 8.9% for the tibialis anterior muscle. Although, investigators failed to detect significant changes in mean muscle strength.2

In July, at the Annual Meeting of the Peripheral Nerve Society in Baltimore, Maryland, Acceleron presented preliminary data from an ongoing phase 2 trial of the therapy in patients with CMT (NCT03124459). This data was from part 1 of the 2-part trial, with part 2 initiated in the third quarter of 2018.3

Part 1 of the phase 2 trial was an open-label, dose-escalation study that enrolled a total of 18 patients—3 cohorts of 6 patients each—with CMT1 or CMTX who received ACE-083 at dose levels of 150 mg, 200 mg, or 240 mg. It showed that the mean total muscle volume increases ranged from 12.6% to 14.2%, and mean absolute decreases in fat friction ranged from 1.7% to 3.5%. As well, treatment with ACE-083 showed mean improvements from baseline in contractile muscle volume ranging from 15.8% to 19.6%.

In terms of AEs, the therapy was well tolerated in phase 2 as well. The most common AEs were injection-site reactions, muscle spasms, and myalgia—all of which were mild or moderate in severity.

“There are currently no FDA-approved therapies for patients with CMT with muscle weakness. The muscle volume and fat fraction changes demonstrated in Part 1 of the ACE-083 trial are encouraging,” Florian P. Thomas, MD, a neurologist and principal investigator at Hackensack Meridian School of Medicine at Seton Hall University, said in July. “We’re hopeful that ACE-083 may become an important option for patients.”

Part 2 of the phase 2 trial is set to be a double-blind, placebo-controlled phase which will enroll approximately 40 patients. They will be randomized 1:1 to receive either placebo or ACE-083 and will be evaluated for changes in muscle volume, fat fraction, strength, function, and safety over a 6-month primary treatment period. That will then be followed by a 6-month open-label treatment period.

ACE-083 is also being assessed in facioscapulohumeral muscular dystrophy (FSHD), with a trial currently in phase 2. Results of that study are expected in the second half of 2019. The FDA has also granted the therapy Fast Track and Orphan Drug designations for FSHD.


1. Acceleron Receives FDA Fast Track Designation for ACE-083 in Charcot-Marie-Tooth Disease [press release]. Cambridge, MA: Acceleron Pharma Inc; Published November 28, 2018. Accessed November 30, 2018.

2. Glasser CR, Gartner MR, Wilson D, Miller B, Sherman ML, Attie KM. Locally acting ACE-083 increases muscle volume in healthy volunteers. Muscle Nerve. 2018;57(6):921-926.


: 10.1002/mus.26113

3. Acceleron Announces Preliminary Results from Part 1 of the ACE-083 Phase 2 Trial in Patients with Charcot-Marie-Tooth Disease at the 2018 Annual Meeting of the Peripheral Nerve Society [press release]. Cambridge, MA: Acceleron Pharma Inc; Published July 23, 2018. Accessed November 30, 2018.

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