SS-31 research and evidence overview

SS-31 is the research designation for elamipretide, and it has a real drug development history rather than a preclinical one. In September 2025 the FDA granted accelerated approval to Forzinity (elamipretide) for Barth syndrome — the first approved mitochondria-targeted therapeutic. In the larger and more general indication, primary mitochondrial myopathy, the phase 3 trial missed both of its primary endpoints outright. That combination is the most useful thing to know about this compound: it works well enough in one ultra-rare genetic disease to clear an accelerated-approval bar, and it did not improve walking distance or fatigue in a 218-patient trial of a broader population.

Elamipretide belongs to the SS (Szeto-Schiller) peptide series: small, cell-permeable, aromatic-cationic peptides that concentrate in the inner mitochondrial membrane and bind cardiolipin, the phospholipid that organises the electron transport chain's supercomplexes. Hazel Szeto's 2018 review in Protein and Peptide Letters, Stealth Peptides Target Cellular Powerhouses to Fight Rare and Common Age-Related Diseases, summarises the preclinical case: in disease models the peptides improve electron-transport efficiency and ATP production, reduce reactive oxygen species, and limit the downstream inflammation and tissue remodelling that follow mitochondrial injury.

The review is written by the peptide series' inventor, and its evidence is animal and cellular. It explains why cardiolipin is a plausible target; it is not a source for clinical effect sizes.

Barth syndrome is an X-linked TAFAZZIN disorder in which cardiolipin remodelling fails — mechanistically the closest possible match for a cardiolipin-binding drug, and a population of roughly 150 people in the United States.

TAZPOWER was a 28-week randomized, double-blind, placebo-controlled crossover trial followed by a 168-week open-label extension. Ten patients entered the extension on 40 mg subcutaneous elamipretide daily and eight reached week 168. Reported outcomes included a cumulative 96.1 m improvement on the six-minute walk test at week 168 (P=0.003), fatigue scores below baseline at all timepoints, improvements in 3D left ventricular volumes, and movement in the monolysocardiolipin/cardiolipin ratio (Thompson et al., Genetics in Medicine, 2024). An eight-patient open-label extension with no placebo group is weak evidence by ordinary standards — which is precisely the trade-off accelerated approval is designed for in an ultra-rare disease.

The approved label reflects that. Forzinity is indicated to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg, granted accelerated approval on the basis of improved knee extensor muscle strength as an intermediate endpoint, with continued approval potentially contingent on confirmatory trials. Labelled warnings include benzyl alcohol toxicity (not for neonates), serious hypersensitivity reactions, and eosinophilia (Forzinity prescribing information, DailyMed).

MMPOWER-3 was the pivotal phase 3 trial in genetically confirmed primary mitochondrial myopathy: 218 participants randomized 1:1 to 40 mg/day subcutaneous elamipretide or placebo for 24 weeks, mean age 45.6 years, 74% with mtDNA alterations. Co-primary endpoints were change in six-minute walk distance and total fatigue score.

It missed both. The between-group difference in 6MWT was −3.2 m (95% CI −18.7 to 12.3; P=0.69) and in total fatigue score −0.07 (95% CI −0.10 to 0.26; P=0.37). The trial was rated Class I evidence that elamipretide does not improve these outcomes at 24 weeks. Tolerability was good, with most adverse events mild to moderate (Karaa et al., Neurology, 2023).

Earlier elamipretide programmes in heart failure with preserved ejection fraction and in dry age-related macular degeneration have likewise not produced an approval.

• The approval is narrow: one ultra-rare genetic disease, a weight threshold, and a muscle-strength endpoint. It is not an endorsement of elamipretide for aging, fatigue, or general mitochondrial support.
• The largest well-controlled trial in people with genuine mitochondrial disease was negative — a strong argument against expecting benefit in healthy adults.
• Approved product is a specified 40 mg/mL sterile formulation with a label, dose adjustment for severe renal impairment, and known warnings. Research-grade SS-31 is none of those things.
• Safety data come from monitored trials in supervised settings, including hypersensitivity reactions that required emergency treatment.