Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial

Karaa A, Bertini E, Carelli V, et al. · Neurology

The largest elamipretide trial failed both primary endpoints: 6-minute walk difference −3.2 m versus placebo (95% CI −18.7 to 12.3, p = 0.69) and no fatigue benefit — Class I evidence of no effect in the indication closest to its mechanism. Well tolerated, but adverse events were near-universal on drug (97.2% treatment-related), led by injection-site reactions, with more discontinuations than placebo (7.3% vs 1.8%).

Population

218 adults with genetically confirmed primary mitochondrial myopathy, 27 sites

Intervention

Elamipretide 40 mg subcutaneous daily for 24 weeks

Comparator

Placebo

Limitations

Sponsor-run with extensive investigator conflicts; a null in myopathy does not test joints, but it is the strongest human efficacy readout for the compound and it was negative.