Elamipretide (SS-31): The Phase 3 Trial That Missed Both Endpoints

Elamipretide, also called SS‑31, is sold to consumers as a mitochondrial peptide on the strength of laboratory findings, as is MOTS-c. It has something almost no research-use peptide has: a completed pivotal phase 3 trial, randomized, double-blind and placebo-controlled, in 218 people. It missed both of its primary endpoints. The difference in six-minute walk distance was −3.2 meters, on the placebo side of zero, with a p value of 0.69.^[1]

What MMPOWER-3 tested

The trial enrolled people with genetically confirmed primary mitochondrial myopathy, a group of inherited disorders that impair mitochondrial energy production and reduce exercise capacity. Participants were randomized one-to-one to 24 weeks of subcutaneous elamipretide at 40 mg/day or placebo. 109 received the drug and 109 the placebo; mean age was 45.6, and 74% had mitochondrial DNA alterations.^[1]

The two primary endpoints were distance walked on the six-minute walk test and total fatigue on a symptom assessment built for this condition. Both are the right kind of endpoint, because they measure what a person can do and how they feel, not a marker in blood.

What the trial does and does not settle

A negative result can be over-read as readily as a positive one, so precision matters in both directions.

• What it settles: in genetically confirmed primary mitochondrial myopathy, 40 mg/day of elamipretide for 24 weeks did not improve walking distance or fatigue against placebo.
• What it does not settle: the trial says nothing directly about weight loss, aging, athletic recovery or general fatigue. It studied none of them, and the compound is marketed for all of them.
• That gap does not help the marketing. Primary mitochondrial myopathy is a population where mitochondrial function is measurably impaired and the drug was given its best chance, and that is where it failed.
• A mechanism that works in cells is a hypothesis, and MMPOWER-3 tested that hypothesis properly in people.

In 218 people with primary mitochondrial myopathy, the six-minute walk result was −3.2 meters, on the placebo side of zero.

Elamipretide does have one FDA approval, and it is narrow. As Forzinity, it received accelerated approval in 2025 to improve muscle strength in adults and children with Barth syndrome (a rare inherited disorder) who weigh at least 30 kg. That approval rests on knee muscle strength, an intermediate endpoint, and continued approval may depend on a confirmatory trial.^[2] It is not approved for weight loss, fatigue, aging or primary mitochondrial myopathy. The SS‑31 sold to consumers for those uses is a research chemical, outside any manufacturing standard applying to prescription drugs, which is a separate problem from whether it works. Our page on what FDA actually said about BPC-157 covers the regulatory position for research-use peptides generally, and our SS-31 profile sets out the Forzinity label and the compounding record.