FDA Grants Orphan Drug Designation to ACE-083 for FSHD Treatment

This morning, the US Food and Drug Administration (FDA) granted an orphan drug designation to Acceleron Pharma Inc. for its product, ACE-083, for the treatment of facioscapulohumeral muscular dystrophy (FSHD), a rare genetic muscle disorder for which there is no current approved treatments.

Based on the naturally-occurring protein follistatin, ACE-083 is a locally-acting therapeutic candidate that utilizes the "Myostatin+" approach to inhibit multiple TGF-beta ligand. It is engineered to have a concentrated effect along targeted muscles to maximize growth and strength selectively in the muscles it is injected to.

“We are pleased to receive orphan drug designation for ACE-083, which has shown the potential to address an area of high unmet medical need,” commented Robert K. Zeldin, MD, chief medical officer of Acceleron, in a recent statement. “We believe that ACE-083 could become an important new treatment for patients with FSHD whose muscle weakness negatively affects their functional abilities.”

The orphan drug designation partly comes from the positive results displayed in part 1 of the 2-part phase 2 trial. Part 1 is the dose escalation, open-label portion of the trial, which consists of 6 cohorts with patients receiving ascending dose levels of ACE-083 in either the tibialis anterior (TA) or biceps brachii (BB) muscle.

Preliminary results from part 1 included data collected from 23 patients evaluable for magnetic resonance imaging (MRI) among 2 cohorts: those with tibialis anterior weakness (11) and those with biceps brachii weakness (12). The patients received 150 mg or 200 mg of ACE-083 via injection once every 3 weeks for the duration of 12 weeks.

They found that the tibialis anterior (TA) cohorts generated a mean total muscle volume increase of 12.6% and produced a mean decrease or improvement in muscle fat fraction of 5.3%. In addition, the biceps brachii (BB) cohorts generated a mean total muscle volume increase of 13.2% and produced a mean decrease or improvement in muscle fat fraction of 0.6%.

In part 2, the randomized, double-blind, placebo-controlled with open-label extension portion of the trial, subjects who safely and successfully complete Part 1 will be randomized (1:1) and administered either ACE-083 (n=14/muscle) or placebo (n=14/muscle) bilaterally to either the TA or BB muscles (but not both). Patients will be administered the blinded study drug once every 3 weeks for approximately 6 months (9 doses). Part 2 will go on for a time duration of approximately 24 weeks, which will include a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose.

Primary outcome measures include the safety and tolerability of ACE-083 with data collection on the incidence, nature, and severity of adverse events in the time frame of 141 days.

Secondary outcome measures include the estimation of systemic exposure to ACE-083 following local intramuscular administration, the percent change from baseline in strength of injected muscle, the percent change from baseline in function of injected muscle, and the change from baseline in patient-reported outcome (PRO) measures in the time frame of 141 days.

To date, the final Part 1 results are anticipated in the second of half of 2018, and the preliminary results from Part 2 of the trial in patients with FSHD are anticipated in the second half of 2019.