A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy.
Level 2 - randomized trial
Individual double-blind randomized crossover trial
PubMed 32096613 · doi:10.1002/jcsm.12559
What was done
MMPOWER-2 was a randomized, double-blind, placebo-controlled crossover trial assessing subcutaneous (SC) elamipretide (40 mg/day) in 30 adults with genetically confirmed primary mitochondrial myopathy. Participants received 4 weeks of elamipretide followed by 4 weeks of placebo, separated by a 4-week washout period, or the reverse sequence. The primary endpoint was distance walked on the 6-minute walk test (6MWT). Secondary outcomes included patient-reported fatigue measures, functional mobility assessments, accelerometry, and adverse events.
What was found
On the primary endpoint, the 6MWT distance was 398.3 (±134.16) meters on elamipretide versus 378.5 (±125.10) meters on placebo, a difference of 19.8 m (95% CI, -2.8 to 42.5; P = 0.0833). Significant benefits favoring elamipretide were observed across patient-reported outcomes: Primary Mitochondrial Myopathy Symptom Assessment Total Fatigue (P = 0.0006), Total Fatigue During Activities (P = 0.0018), Neuro-QoL Fatigue Short Form (P = 0.0115), and Patient Global Assessment (P = 0.0421). No significant changes were found for Physician Global Assessment (P = 0.0636), Triple Timed Up and Go (P = 0.8423), or wrist/hip accelerometry (P = 0.9345 and P = 0.7326). Injection site reactions occurred in 80% of elamipretide treatments (mostly mild), with no serious adverse events or deaths.
Why it matters
This Phase 2 study identified symptom-level improvements in fatigue and established dosing feasibility, providing preliminary signal data to guide a longer Phase 3 trial (MMPOWER-3) for a condition with limited therapeutic options.
Limits
The trial had a small sample size (n = 30) and a short treatment duration (4 weeks). The primary objective functional endpoint (6MWT) did not achieve statistical significance, and objective activity monitoring (accelerometry) and physical mobility tests showed no measurable benefit. Injection site reactions were very common.
Cited by
- supports Clinical trials of SS-31 as a treatment for mitochondrial disease have mostly been negative.