FDA Grants Fast Track Designation to FSHD Therapy

This morning, Acceleron Pharma announced that the US Food and Drug Administration (FDA) has granted Fast Track designation to ACE-083 for the treatment of patients with facioscapulohumeral muscular dystrophy (FSHD).

“This is an important milestone in the development of ACE-083—our lead program within our neuromuscular franchise,” said Matthew Sherman, Chief Medical Officer of Acceleron in a press release. “FSHD is a serious and rare neuromuscular disorder for which there are currently no approved therapies available. With this designation, we will be able to expedite the FDA review process of ACE-083, and if successful, deliver the first locally-acting, ‘Myostatin+’ muscle agent as a meaningful treatment option for the thousands of patients impacted by FSHD.”

FSHD is a rare, genetic muscle disorder, and the primary clinical presentation of the condition is debilitating skeletal muscle weakness and loss. The symptoms of FSHD develop in a descending pattern, beginning with the face and upper body and progressing to the lower body in a “muscle by muscle” fashion.

ACE-083 consists of the naturally-occurring protein follistatin, which inhibits multiple TGF-beta ligands. It is being developed to have a concentrated effect along targeted muscles to maximize growth and strength selectively in the muscles into which the drug is administered.

ACE-083 is a locally-acting “Myostatin+” muscle agent and is currently being evaluated in a pair of Phase 2 trials: one in FSHD and a second in Charcot-Marie Tooth (CMT) disease.

Study A083-02 will be a multicenter, Phase 2 study to evaluate the safety, tolerability, pharmacodynamics (PD), efficacy, and pharmacokinetics (PK) of ACE 083 in patients with FSHD to be conducted in two parts. Part 1 will be open-label, dose-escalation, and Part 2 will be randomized, double-blind, and placebo-controlled.

Part 1 will be the open-label, dose escalation portion of the study and will consist of up to 6 cohorts of patients. It will aim to evaluate multiple ascending dose levels of ACE-083 in either the tibialis anterior (TA) or biceps brachii (BB) muscle. Patients in each of the 6 cohorts will be enrolled in a 4-week screening period before beginning treatment. A Safety Review Team (SRT) will meet to review data for each cohort when at least 4 patients within a cohort have completed their Day 43 visit prior to dose escalation.

Study duration for Part 1 for each patient will be an estimated 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period following the final dose.

Part 2 will be the randomized, double-blind, placebo-controlled portion of the study and will include an open-label extension (OLE). Prior to the start of Part 2, a review of safety and efficacy data from Part 1 will be conducted to establish whether cohorts for one or both muscles will be pursued in Part 2. Additionally, the evaluation will provide the suggested dose level for each muscle. A total of up to 56 new patients (28 patients per muscle) could potentially be enrolled and randomized (1:1) to receive either ACE-083 (n=14/muscle) or placebo (n=14/muscle) bilaterally to either the TA or BB muscles (but not both). Patients will receive blinded study drug once every 3 weeks for approximately 6 months (9 doses). Study duration for Part 2 for each patient will be approximately 15 months, including a 1-month screening period, a 12-month treatment period (6-month double-blind, placebo-controlled, and a 6-month open-label extension), and a 2-month follow-up period after the last dose.

It is Acceleron’s belief that improved muscle strength in target muscles will be exhibited in this study and may provide a clinical benefit and enhance quality of life.

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