Facioscapulohumeral muscular dystrophy (FSH or FSHD) is characterised by a selective muscle deficit (muscles of the face, shoulders and arms). This characteristic was an advantage to candidate for evaluating the efficacy of ACE-083, a molecule developed by the Acceleron laboratory, which, when administered intramuscularly, has a local anti-myostatin action.
In 2016, a phase II clinical trial started, in two parts:
- the first to evaluate for 3 months the tolerance of ACE-083 and to find the optimal dose in 37 patients with FSH ;
- the second to test this optimal dose in a double-blind, placebo-controlled manner for 6 months and then open-label for a further 6 months in 55 patients receiving 1 injection every 3 weeks in the biceps brachii or tibialis anterior.
Muscle strength, the glass ceiling of anti-myostatins?
Preliminary results, presented in 2019, had shown a dose-dependent increase in the volume of treated muscles (greater than 15% at doses of 200 to 240 mg per muscle) and a reduction in the level of fat in the anterior tibial muscles. However, according to the final results of the trial published in spring 2022, this increase in volume (the primary endpoint of the trial) was not accompanied by a significant improvement in functional scores, nor in the FSHD-Health Index, a score with which patients assess the impact of the disease.
Acceleron has announced that it is discontinuing the development of ACE-083 in FSH, but also in Charcot-Marie-Tooth disease.
Acceleron Announces Topline Results from the Phase 2 Trial of ACE-083 in Patients with Facioscapulohumeral Muscular Dystrophy. Press release, 16 September 2019.