Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy

This phase I/II, multicenter, randomized, double-blind clinical trial evaluated the safety, tolerability, and preliminary efficacy of elamipretide (SS-31) in 36 adults with genetically confirmed primary mitochondrial myopathy. The study used a dose-escalation design, with participants receiving subcutaneous injections of elamipretide at different dosages or placebo for 5 days, followed by monitoring.

The primary endpoint was the 6-minute walk test (6MWT), a validated functional measure for assessing exercise capacity. Participants treated with elamipretide demonstrated improvement in distance walked compared to placebo, with the most pronounced effect at the highest doses. The safety profile was favorable across all doses tested.

• Elamipretide was well tolerated, with predominantly mild adverse events (injection site reactions)
• Biomarkers of mitochondrial function showed a trend toward improvement
• The study established the basis for subsequent phase 2/3 trials (MMPOWER)
• No serious drug-related adverse events were reported

This work was pioneering in clinically testing a peptide targeting mitochondrial cardiolipin in patients with mitochondrial myopathy, a condition for which no approved treatments existed. The encouraging results supported the continued clinical development of elamipretide for mitochondrial diseases.