What it is
SS-31, now called elamipretide, is a very small lab-made peptide: four amino acids long. It was designed to slip into mitochondria, the structures inside cells that make energy, and to stick to a fat molecule called cardiolipin that sits in their inner wall. Cardiolipin helps hold the energy-making machinery together, and it is faulty in a rare inherited disease called Barth syndrome.
In September 2025 the FDA approved elamipretide under the brand name Forzinity, as a once-daily injection to improve muscle strength in people with Barth syndrome who weigh at least 30 kg. The approval is an “accelerated” one, meaning it rests on an early signal and must be confirmed by a further trial. It is the only approved use.
Elamipretide is the tetrapeptide D-Arg-Dmt-Lys-Phe-NH2 (Dmt, 2,6-dimethyltyrosine; C32H49N9O5, 639.8 g/mol), one of the Szeto-Schiller peptides. Its alternating aromatic and cationic residues give a net +3 charge at physiological pH; the SS peptides are cell-permeable and were reported to concentrate about 1000-fold in the inner mitochondrial membrane (Zhao et al., J Biol Chem 2004). It binds cardiolipin through electrostatic and hydrophobic interactions; the label describes it as a mitochondrial cardiolipin binder that improves mitochondrial morphology and function. Preclinical work proposes that binding prevents cardiolipin from converting cytochrome c into a peroxidase.
Label pharmacokinetics: after subcutaneous injection, peak concentrations occur at 0.5–1 hour and absolute bioavailability is about 92%. Volume of distribution is about 0.5 L/kg and plasma protein binding about 39%. Elamipretide is degraded from the C-terminus to inactive tri- and dipeptide metabolites, and about 100% of a dose is recovered in urine within 48 hours. Exposure rises with renal impairment, and the label halves the dose when eGFR is under 30 mL/min without dialysis.
Who made it and when
The peptide came out of a long collaboration between Hazel Szeto, a pharmacologist at Weill Cornell Medical College in New York, and Peter Schiller, a peptide chemist in Montreal; “SS” stands for Szeto-Schiller. Their family of small peptides was built from alternating ring-shaped and positively charged amino acids, and some of them turned out to gather inside mitochondria. The key paper describing these peptides as mitochondria-targeted compounds appeared in 2004.
A Massachusetts company, Stealth BioTherapeutics, took the compound into human trials under the names MTP-131 and Bendavia, and later elamipretide. After trials in heart and kidney conditions, the company focused on rare mitochondrial diseases and on a form of age-related vision loss.
The Szeto-Schiller peptides were developed jointly at Weill Cornell and the Clinical Research Institute of Montreal. Zhao et al. (J Biol Chem 2004) reported that these cell-permeable peptides, built on alternating aromatic and basic residues with dimethyltyrosine, localise to the inner mitochondrial membrane, reduce mitochondrial ROS, inhibit permeability transition and swelling, and improved contractile force in an ex-vivo reperfused heart. Szeto’s 2014 review in the British Journal of Pharmacology describes SS-31 as the first cardiolipin-protective compound. The early US patent covering the peptides’ use to prevent mitochondrial permeability transition (US 7,576,061; Cornell Research Foundation and IRCM; priority 2003) is one of six US patents listed on the Forzinity label; Google Patents gives its expiry as 2026-01-20.
Stealth BioTherapeutics ran studies in reperfusion injury during coronary intervention (EMBRACE STEMI) and renal-artery angioplasty (EVOLVE), heart failure and skeletal muscle function in older adults before concentrating on primary mitochondrial myopathy, Barth syndrome and dry age-related macular degeneration. The Barth syndrome NDA (215244) was submitted on 2024-01-29, received a complete response on 2025-05-15, and was approved under the accelerated pathway on 2025-09-19, with a rare pediatric disease priority review voucher.
What the data say
The approval rests on very few people. Barth syndrome is ultra-rare, and the key trial had 12 patients. In the blinded part, where patients swapped between the drug and a dummy injection for 12 weeks each, the drug did not beat placebo on its two main goals, walking distance and fatigue. Leg-muscle strength rose later, during several years of open-label treatment when everyone knew they were on the drug. That later gain is what the FDA accepted as an early sign of effect.
Elsewhere the record is mixed. A large trial in adults with inherited mitochondrial muscle disease was negative. A vision trial in dry macular degeneration missed its main goals, and a larger one is still running.
TAZPOWER (NCT03098797): 12 males with Barth syndrome received 40 mg subcutaneously daily in a 12-week crossover. Neither primary endpoint (6MWT, BTHS-SA total fatigue) was met. In the open-label extension, 6MWT improved by 95.9 m at 36 weeks (p = 0.024), and the label reports median knee extensor strength gains of 34 to 68 newtons from weeks 12 to 168 against a baseline of 124 N, as descriptive statistics without a control group.
MMPOWER-3 (NCT03323749; n=218): at 24 weeks the least-squares 6MWT difference was −3.2 m (p = 0.69) and PMMSA fatigue did not differ. NuPOWER (NCT05162768; n=102, 60 mg daily, nuclear-DNA disease) has no posted results.
ReCLAIM-2 (NCT03891875; n=176): no significant effect on low-luminance visual acuity or geographic atrophy growth at 48 weeks; ellipsoid-zone loss progressed about 43% more slowly (nominal p = 0.0034). ReNEW (NCT06373731; n=313) has as its registered primary endpoint the week-48 rate of change in the macular area of photoreceptor loss, the ellipsoid-zone measure that Ehlers et al. said would serve as the Phase 3 primary endpoint.
Safety: injection-site reactions occurred in all treated Barth patients; hypersensitivity and eosinophilia are labeled.
Regulatory picture
Elamipretide is FDA approved, but only for one narrow use: improving muscle strength in children and adults with Barth syndrome who weigh at least 30 kg. The approval is conditional. The FDA first turned the application down in May 2025, then granted accelerated approval in September 2025 based on the muscle-strength data, and required the company to run a new placebo-controlled trial. If that trial fails to confirm a real effect, the FDA can withdraw the approval. The confirmatory trial began enrolling in 2026.
It is not approved for mitochondrial myopathy, macular degeneration or anything else. Because an approved product exists, pharmacies may not make copies of it regularly or in large amounts unless it is on the FDA’s drug shortage list.
Approval: Forzinity (elamipretide) injection, NDA 215244, accelerated approval under section 506(c) and 21 CFR 314.510 on 2025-09-19 for adult and pediatric Barth syndrome patients weighing at least 30 kg, based on knee extensor strength as an intermediate clinical endpoint. The postmarketing requirement is a randomized, double-blind, placebo-controlled trial, with study completion scheduled for 09/2029; 4TAZPower (NCT07531251, Phase 3b/4, ages 5–55) began in July 2026. The labeled dosage is 40 mg subcutaneously once daily, or 20 mg with eGFR under 30 mL/min not on dialysis.
Compounding: elamipretide is not on the 503A bulks list or in any 503A nomination category. Because it is the active ingredient of an approved drug, section 503A bars compounding drugs that are essentially copies of it regularly or in inordinate amounts while it is commercially available (a product on FDA’s drug shortage list does not count as commercially available), so this article records it as restricted.
Other programmes: none of the other indications has been filed or approved. No approval outside the US was verified for this article.
