An oral small molecule myosin inhibitor, EDG-5506 can offer protection to injury-susceptible fast skeletal muscle fibres in dystrophinopathies such as Duchenne muscular dystrophy (DMD) and BMD.
The open-label, single-centre study analysed the safety, tolerability, effect on muscle damage biomarkers and pharmacokinetics (PK) of EDG-5506 in BMD patients.
It enrolled 12 patients, including all seven subjects from a Phase Ib clinical trial, and were given 10mg oral doses of EDG-5506 daily at night.
According to the findings, EDG-5506 was found to be well-tolerated without any serious adverse events, discontinuations or dose reductions reported.
Dizziness and somnolence were reported to be the most common adverse events seen following administration of the 10mg dose of the therapy.
Subsequently, all subjects were dose escalated to receive a 15mg daily dose of the treatment according to the protocol.
The two-month plasma PK findings for the 10mg dose of EDG-5506 demonstrated exposure levels that were nearly 61% of those seen in the Phase Ib trial of once-a-day 20mg EDG-5506 given for two weeks.
The decreased exposure for BMD subjects in the ARCH study is in line with the 10mg dose of the therapy and a shorter half-life of EDG-5506 in BMD subjects, likely linked with a lowered overall muscle mass.
Furthermore, EDG-5506 treatment caused a substantial decline in key biomarkers of muscle damage.
Activity levels found at two months of EDG-5506 dosage was higher than activity levels at one month and activity levels reported in subjects in the Phase 1b trial, even with reduced overall exposure to EDG-5506.
Edgewise chief medical officer Joanne Donovan said: “The magnitude of reduction in biomarkers of muscle damage in adults with BMD is consistent with our observations in the Phase Ib trial.
“We’re encouraged by the decrease in biomarkers particularly in the context of the increased activity observed in BMD patients treated with EDG-5506.”