Acceleron’s ACE-083 Therapy Candidate for FSHD Earns FDA’s Fast Track Designation

The U.S. Food and Drug Administration (FDA) recently granted fast track designation to Acceleron Pharma’s ACE-083 for the treatment of facioscapulohumeral muscular dystrophy (FSHD).

ACE-083 is a locally-acting agent that binds to and inhibits proteins in the transforming growth factor (TGF)-beta family, such as myostatin, which reduce muscle strength and growth.

The therapy candidate is designed to have a concentrated effect along targeted muscles to maximize growth and strength.

ACE-083 is being developed to treat conditions in which improved muscle strength is necessary to achieve clinical benefit and increase quality of life. In FSHD, patients suffer from debilitating skeletal muscle weakness and loss. The symptoms often begin in the face and upper body, eventually progressing to the lower body, affecting one muscle group at a time.

“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,” Matthew Sherman, MD, Acceleron’s chief medical officer, said in a press release.

A fast track designation is a process designed to facilitate the development and expedite the review of new drugs that show evidence of providing a new treatment for conditions with serious unmet needs.

In a two-part Phase 2 clinical trial (NCT02927080) in FSHD, ACE-083 has shown it is safe and effective at increasing muscle mass and diminishing muscle fat.

The trial, now recruiting patients for its second part, was designed to have a first dose-escalation Part 1, and a second randomized, double-blind, placebo-controlled with open-label extension Part 2.

In Part 1, six groups (A to F) of patients tested multiple ascending doses of ACE-083 in two muscles —  tibialis anterior and biceps brachii.

Weakness in the lower leg’s tibialis anterior muscle is the main reason FSHD patients experience dorsiflexion, or an inability to lift the front of their foot when taking a step. The upper arm’s biceps brachii is the muscle that allows people to bend their elbow.

Study duration for Part 1 was approximately 24 weeks, including a pre-treatment four-week screening period, a 12-week treatment period and an eight-week follow-up period after the last dose.

A safety review team (SRT) met to review data for each group when at last four patients completed their day-43 visit prior to dose escalation.

Preliminary results covering the first part of the trial demonstrated positive safety and tolerability along with unprecedented mean increases in total muscle volume of more than 12 percent in the two muscles evaluated.

A total of 23 patients enrolled in the first part of the trial, 11 with lower leg weakness and 12 with upper arm weakness. Some received 150-mg doses and some 200 mg.

ACE-083 increased tibialis anterior muscle mass by 12.6 percent, the trial showed. It also helped decrease the amount of muscle fat by 5.3 percent. The therapy also increased the upper arm’s biceps brachii mass by 13.2 percent and decreased the amount of fat in the biceps by 0.6 percent.

Acceleron will start the second part of the trial in the second quarter of 2018. Up to 56 new patients will be enrolled here (28 patients per muscle) and randomized 1:1 to receive either ACE-083 or placebo. Patients will receive a total of nine doses — once every three weeks for approximately six months.

Patients who complete the double-blind treatment period will advance to open-label treatment with ACE-083, receiving the same dose of active drug in both muscles once every three weeks for six months.