Evidence Grade C — Moderate human evidence. 274 published studies, 108 human. 1 registered clinical trial.
Medically reviewed by a licensed medical professional
SS-31 is the research name for elamipretide, a peptide that targets mitochondrial membranes. A pharmaceutical version (Forzinity) has received regulatory authorisation for Barth syndrome, a rare genetic mitochondrial disease. This entry covers SS-31 in its broader research and unregulated context — available through unregulated channels for purposes beyond the narrow authorised indication.
SS-31 (Research Grade Elamipretide) is also known by these brand and alternate names:
274 published studies: 108 human, 113 animal, 52 in-vitro, 41 reviews
Elamipretide has received FDA approval for Barth syndrome under the brand name Forzinity, based on open-label extension data showing improved walking distance and muscle strength. A larger Phase III trial in primary mitochondrial myopathy (218 patients) did not meet its primary endpoint, and the drug was not approved for that broader indication.
SS-31 is available through unregulated channels for purposes beyond the approved Barth syndrome indication. The failed Phase III trial in primary mitochondrial myopathy demonstrates that mitochondrial targeting does not guarantee clinical benefit across all mitochondrial conditions. Products from unregulated sources lack pharmaceutical quality assurance.
Elamipretide binds to cardiolipin, a unique phospholipid in the inner mitochondrial membrane, stabilising the membrane structure that is essential for energy production. This mechanism is well characterised from the approved product's development. The drug restores mitochondrial function at its structural foundation rather than targeting a specific enzyme.
Research suggests the pharmaceutical version's approval for Barth syndrome validates the mitochondria-targeting mechanism, but a larger Phase III trial in primary mitochondrial myopathy (218 patients) failed its primary endpoint — demonstrating that mitochondrial targeting does not automatically translate to benefit across all mitochondrial conditions. Every randomised placebo-controlled portion of every major elamipretide trial failed primary endpoints; positive signals came from open-label extensions and post-hoc analyses. The Barth syndrome approval rests on a surrogate endpoint in just 8 patients who completed the open-label extension. Products from unregulated sources lack pharmaceutical quality assurance and are used for indications without clinical trial support.
PeptideTrace tracks 1 registered clinical trial for SS-31 (Research Grade Elamipretide) sourced from ClinicalTrials.gov.
FRDA Investigator Initiated Study (IIS) With Elamipretide
FDA ORIG 1
SS-31 (elamipretide, now branded FORZINITY) is a mitochondria-targeted tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyltyrosine). Its molecular formula is C32H49N9O5 with a molecular weight of 639.8 Da (CAS 736992-21-5). Subcutaneous bioavailability is approximately 90-92%. Discovered by Hazel H. Szeto and Peter W. Schiller at Weill Cornell Medical College, developed by Stealth BioTherapeutics. Research suggests FDA accelerated approval was granted September 2025 for Barth syndrome, making it the first FDA-approved mitochondria-targeted therapeutic. Continued approval is contingent on a confirmatory trial.
Elamipretide selectively and reversibly binds cardiolipin and monolysocardiolipin (MLCL) in the inner mitochondrial membrane. This stabilizes mitochondrial cristae structure and normalizes inner membrane morphology. Research suggests it stabilizes cytochrome c conformation, improves electron transport chain complex assembly and supercomplex function, enhances oxidative phosphorylation coupling, increases ATP production, and reduces pathogenic reactive oxygen species. The alternating cationic-aromatic motif enables cell penetration into cardiomyocytes, endothelial cells, neurons, myotubes, and macrophages. Research suggests the compound has no significant opioid receptor binding.
The TAZPOWER trial (Phase 2/3, N=12 Barth syndrome) forms the basis for FDA approval. The randomized crossover phase did not meet primary endpoints, but the open-label extension (N=8, 168 weeks) showed mean 6MWT improvement of 96.1 meters (p=0.003) and knee extensor strength improvement of 63 Newtons (>45%). MMPOWER-3 (Phase 3, N=218 primary mitochondrial myopathy) failed both co-primary endpoints (6MWT difference -3.2 m, p=0.69). Post-hoc subgroup analysis suggested benefit in nDNA replisome patients (6MWT +37.3 m). PROGRESS-HF (Phase 2, N=71 HFrEF) found no significant changes. The NuPOWER trial targets genetic subtypes.
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism. In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.
This content is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making decisions about your health.
