Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial.
Level 2 - randomized trial
Individual phase 3 randomized, double-blind, placebo-controlled trial
PubMed 37268435 · doi:10.1212/WNL.0000000000207402
What was done
In a phase-3, randomized, double-blind, placebo-controlled clinical trial (MMPOWER-3), 218 participants with genetically confirmed primary mitochondrial myopathy (PMM) were randomized 1:1 to receive 24 weeks of daily subcutaneous elamipretide (40 mg/d, n = 109) or placebo (n = 109). The population had a mean age of 45.6 years, was 64% women, 94% White, and had either mitochondrial DNA (74%) or nuclear DNA (26%) defects. Co-primary endpoints were change from baseline to week 24 in distance walked on the 6-minute walk test (6MWT) and total fatigue score on the Primary Mitochondrial Myopathy Symptom Assessment (PMMSA).
What was found
The trial did not meet its primary endpoints. Between elamipretide and placebo, the difference in least squares mean change from baseline to week 24 on the 6MWT was -3.2 meters (95% CI -18.7 to 12.3; p = 0.69), and on the PMMSA total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37). At baseline, the mean 6MWT was 336.7 +/- 81.2 meters and the mean PMMSA total fatigue score was 10.6 +/- 2.5. Elamipretide was well-tolerated, with most adverse events being mild to moderate.
Why it matters
This phase-3 trial provides clear evidence that 24 weeks of subcutaneous elamipretide fails to improve exercise capacity or fatigue over placebo in primary mitochondrial myopathy.
Limits
The study cohort was 94% White, limiting generalizability across diverse racial and ethnic populations. Underlying genetic heterogeneity (mtDNA vs nDNA mutations) was present, and the 24-week follow-up period does not evaluate longer-term treatment effects.
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