Acceleron abandons the development of ACE-083 in the treatment of FSHD

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by a selective muscular deficit (muscles of the face, shoulders and arms). This characteristic made it a good candidate in assessing the efficacy of ACE-083, a drug molecule developed by Acceleron, which, when administered by intramuscular injection, exercises a local myostatin-inhibiting action.

In 2016, a phase II clinical trial began, consisting of two parts:

  • the first part, to evaluate over a 3 month period the tolerability of ACE-083 and to find the optimum dose in 36 patients with FSHD;
  • the second part, to test this optimum dose in a double blind versus placebo trial over a 6 month period in 56 patients receiving 1 injection every 3 weeks in the biceps brachii or the tibialis anterior.

In 2018, this candidate medicine had been granted “fast track” and “orphan drug” designation in FSHD by the American health authorities.

Muscle strength, the glass ceiling of the myostatin inhibitors?
Preliminary results, presented at the medical and scientific conference of the Muscular Dystrophy Association (MDA) in April 2019, showed a dose-dependent increase in the volume of the treated muscles (greater than 15% at doses of 200 to 240 mg per muscle) and a decrease in fat content in the tibialis anterior muscles. However, this increase in volume (primary endpoint of the study) was not accompanied by a significant increase in the strength of the treated muscles (secondary endpoint), as Acceleron announced in a press release on 16 September 2019. This lack of functional effect is not a first for the myostatin inhibitors. It may therefore be necessary to combine them with another drug molecule that is active on the cause of the myopathy.

In the same press release, Acceleron announced that it did not wish to conduct any new ACE-083 clinical trials in FSHD. On the other hand, the phase II clinical trial of the same product in Charcot-Marie-Tooth disease is continuing. Results are expected in the first four months of 2020.

 

Communiqué de presse d’Acceleron du 16 septembre 2019 : « Acceleron Announces Topline Results from the Phase 2 Trial of ACE-083 in Patients with Facioscapulohumeral Muscular Dystrophy »