SS-31

SS-31 is a synthetic, cell-permeable tetrapeptide with the sequence D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2. It is the same molecule as elamipretide, and it has also carried the development codes MTP-131 and Bendavia, plus the brand name Forzinity. In PubChem it is listed as CID 11764719, with molecular formula C32H49N9O5, an average molecular weight of about 639.8 g/mol, and CAS number 736992-21-5. The name SS comes from the inventors Hazel Szeto and Peter Schiller, who identified the compound as part of a series of small aromatic-cationic peptides that concentrate in mitochondria. It was developed by Stealth BioTherapeutics.

SS-31 localizes to the inner mitochondrial membrane and binds selectively and reversibly to cardiolipin, a phospholipid found almost exclusively in that membrane. The interaction combines electrostatic attraction between the peptide's positively charged residues (D-Arg and Lys) and cardiolipin's phosphate head groups with insertion of its aromatic residues into the lipid bilayer. By binding cardiolipin, SS-31 favors the normal electron-carrier function of cytochrome c over its pathological peroxidase function, which in preclinical and biochemical work is associated with better electron transport chain activity, preserved cristae structure, lower mitochondrial reactive oxygen species production, and improved ATP synthesis. Early reports described the peptide as a mitochondria-targeted antioxidant, but later work reframed it as a cardiolipin-protective compound rather than a general free-radical scavenger. The precise molecular details were not fully resolved for years and are still being refined.

Several did. PROGRESS-HF (NCT02788747), a Phase 2 trial in heart failure with reduced ejection fraction, did not meet its primary endpoint of change in left ventricular end-systolic volume at 4 weeks. MMPOWER-3 (NCT03323749), a Phase 3 trial of 40 mg daily subcutaneous elamipretide in 218 participants with primary mitochondrial myopathy, did not meet either of its co-primary endpoints (6-minute walk distance and a fatigue score) at 24 weeks. TAZPOWER (NCT03098797), the pivotal Barth syndrome trial, failed both co-primary endpoints in its randomized double-blind crossover portion, with a 6-minute walk difference versus placebo of -0.8 m (p = 0.97) and a fatigue score difference of +0.06 (p = 0.89). ReCLAIM-2 (NCT03891875), a Phase 2 trial in dry age-related macular degeneration with geographic atrophy, also did not meet its co-primary endpoints. The published conclusions for these trials state plainly that the primary endpoints were not met.

A trial can miss its pre-specified primary endpoint while secondary, exploratory, or open-label analyses suggest a possible effect. These signals do not carry the same weight as a met primary endpoint, because they are not the test the study was designed to pass and often lack a concurrent randomized control. For example, the original MMPOWER dose-escalation study reported a larger mean increase in 6-minute walk distance with elamipretide than placebo, but the difference narrowly missed statistical significance (p = 0.053). In TAZPOWER, the open-label extension showed improvements from baseline in walk distance and muscle strength, yet those results had no randomized comparison group. A post hoc subgroup analysis of MMPOWER-3 suggested a walk-distance benefit in participants with nuclear DNA variants, which became the rationale for a follow-up trial rather than proof of efficacy. These findings are hypothesis-generating and should not be read as confirmed clinical benefit.

Yes, but only for one narrow indication. On September 19, 2025 the FDA granted accelerated approval to elamipretide under the brand name Forzinity (elamipretide hydrochloride injection, NDA 215244, sponsored by Stealth BioTherapeutics) to improve muscle strength in adult and pediatric patients with Barth syndrome who weigh at least 30 kg. This is described as the first FDA-approved therapy for a primary mitochondrial disease. The approval was based on an improvement in knee extensor muscle strength, an intermediate clinical endpoint, rather than on a met primary efficacy endpoint from the main randomized trial. Because it is an accelerated approval, continued approval may be contingent on verification of clinical benefit in a confirmatory trial. The path included an earlier Complete Response Letter before resubmission and approval. Approval for Barth syndrome does not mean efficacy is established for heart failure, primary mitochondrial myopathy, macular degeneration, or any other use, where trials missed their endpoints.

Barth syndrome is a rare X-linked genetic disorder caused by mutations in the tafazzin (TAZ) gene, which impair the remodeling of cardiolipin in the inner mitochondrial membrane. Because SS-31 binds cardiolipin directly, its mechanism is tied conceptually to the defect in Barth syndrome, which is part of why this became its approved indication. Elamipretide is described as the first cardiolipin-directed mitochondrial therapeutic. The approval rests on a small dataset: the pivotal TAZPOWER trial enrolled only 12 participants in its randomized crossover portion, and the supportive strength data came from continued open-label treatment. Stealth also indicated it would work with the FDA on data to potentially extend treatment to Barth syndrome patients weighing less than 30 kg, who fall below the approved label cutoff.

The FDA-approved product (Forzinity) is given by subcutaneous injection at 40 mg once daily for Barth syndrome. After subcutaneous dosing, peak plasma concentrations are reached within about 0.5 to 1 hour, absolute bioavailability is roughly 92 percent, and plasma protein binding is low at about 39 percent. The peptide distributes through total body water, with a volume of distribution around 0.5 L/kg, and it is metabolized by sequential C-terminal degradation to two inactive metabolites that, along with the parent drug, are cleared in the urine (close to 100 percent recovered by 48 hours). Because elimination is renal, the label calls for halving the dose in adults with severe renal impairment not on dialysis. A definitive elimination half-life is not stated in the prescribing information, and reported values conflict across sources, so that parameter should be treated as not firmly established. This page describes what studies and the label report and is not dosing guidance for human use.

SS-31 (elamipretide) is not listed by name on the World Anti-Doping Agency (WADA) Prohibited List. For athletes, the relevant question is the S0 Non-Approved Substances category, which prohibits at all times any pharmacological substance that is not addressed elsewhere on the List and has no current approval by a governmental regulatory health authority for human therapeutic use. The FDA-approved Forzinity product does have an approval, but it is narrowly indicated for Barth syndrome. The widely sold research-only SS-31 products marketed by peptide vendors are not the approved drug, are not quality-assured for human use, and for athletes would fall under the S0 logic. Anyone subject to anti-doping testing should treat the regulatory status as unsettled and verify current rules with the relevant authority.