SS-31 (Elamipretide)

Verified against Two independent authoritative sources agree. PubChem PUG-REST returned CID 11764719 with formula C32H49N9O5 and molecular weight 639.8; its synonym list carries CAS 736992-21-5, the sequence D-Arg-Dmt-Lys-Phe-NH2, and the development codes MTP-131, Bendavia, Ocuvia and RX-31. The FDA Global Substance Registration System record UNII 87GWG91S09 independently gives CAS 736992-21-5, formula C32H49N9O5, molecular weight 639.79, INN 10154 and USAN DE-80. Fields marked “not verified” are ones we could not confirm against a primary chemical database — we leave them blank rather than guess.

Identity and regulatory status

SS-31 is a four-residue peptide, D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2,6-dimethyltyrosine. It belongs to the Szeto–Schiller class of aromatic-cationic peptides built on an alternating aromatic and basic residue motif, carrying a net charge of +3 at neutral pH. PubChem CID 11764719 and FDA GSRS record UNII 87GWG91S09 independently give CAS 736992-21-5, formula C32H49N9O5 and molecular weight 639.79. The molecule has accumulated an unusual number of names across its development history: SS-31, elamipretide, MTP-131, Bendavia, Ocuvia, RX-31 and, since approval, Forzinity.

This is the significant point that most reference pages on this compound omit. Elamipretide hydrochloride received FDA accelerated approval on 19 September 2025, sponsored by Stealth BioTherapeutics, to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg. It is administered by once-daily subcutaneous injection. The approval was granted on the basis of an intermediate clinical endpoint — knee extensor muscle strength — under the accelerated pathway, which means confirmatory evidence is still owed.

Treating this compound as a preclinical research chemical with no human record misstates the evidence position. There are 29 registered clinical trials.

The cardiolipin mechanism

Cardiolipin is an anionic phospholipid found almost exclusively in the inner mitochondrial membrane, where it is required for cristae formation and for organising the respiratory complexes into supercomplexes. Its interaction with cytochrome c determines whether that protein acts as an electron carrier or as a peroxidase, and cardiolipin peroxidation is a documented feature of several conditions involving energy deficit.

Birk and colleagues used a polarity-sensitive fluorescent analogue of SS-31 to demonstrate high-affinity binding to cardiolipin, and showed that the resulting complex inhibited cytochrome c peroxidase activity by protecting its heme iron. In a rat renal ischaemia model, pretreatment protected cristae membranes and prevented mitochondrial swelling, with faster ATP recovery on reperfusion.

The mitochondrial accumulation figures that circulate for this compound trace to two specific measurements, both in isolated systems. Zhao and colleagues in 2004 reported that peptides of this class concentrate 1000-fold in the inner mitochondrial membrane. A separate 2005 paper reported that tritiated SS-31 was concentrated approximately 5000-fold in an isolated mitochondrial pellet, with intracellular concentrations roughly six-fold higher than extracellular in neuronal cell lines. These are two different measurements in two different preparations, and the commonly quoted range of 1000 to 5000-fold merges them.

What the human trials measured

The largest published trial is the one that did not work. MMPOWER-3 randomised 218 adults with genetically confirmed primary mitochondrial myopathy, mean age 45.6 years, 64% women, to 40 mg per day subcutaneously or placebo for 24 weeks. Karaa and colleagues reported that it missed both co-primary endpoints. The difference in six-minute walk distance was −3.2 metres, 95% CI −18.7 to 12.3, p = 0.69. The difference in total fatigue score was −0.07, 95% CI −0.10 to 0.26, p = 0.37. The earlier crossover trial in 30 participants had also missed its primary endpoint, with a six-minute walk difference of 19.8 metres, p = 0.083.

In Barth syndrome, TAZPOWER randomised 12 participants in a crossover design followed by a 168-week open-label extension. Thompson and colleagues reported that ten patients entered the extension and eight reached week 168, with a cumulative improvement of 96.1 metres on the six-minute walk test at that point, p = 0.003. Injection-site reactions were the most frequently recorded adverse event.

In dry age-related macular degeneration, ReCLAIM-2 randomised 176 patients. Ehlers and colleagues reported that the primary endpoints were not met, though a 43% reduction in progression of ellipsoid zone attenuation was recorded at nominal p = 0.0034.

The single human study in healthy older adults

One trial has examined this compound in people without a diagnosed mitochondrial disease. Roshanravan and colleagues randomised 39 healthy adults aged 60 to 85, 46% female, enrolled specifically on the basis of poorly functioning mitochondria, to a single two-hour intravenous infusion or placebo. Mitochondrial capacity in the first dorsal interosseous muscle was measured non-invasively by magnetic resonance and optical spectroscopy.

Maximum ATP production rose relative to placebo immediately after the infusion, with the percentage change reaching p = 0.045. No difference was found at day 7, consistent with the compound's half-life in human blood. Resting mitochondrial coupling did not change significantly. Critically, despite the rise in ATP capacity, there was no significant effect on volitional fatigue resistance measured by force-time integral over repeated muscle contractions.

That last finding is the one worth holding onto: a measurable change in a mitochondrial parameter did not produce a measurable change in the functional outcome it was expected to drive. The same dissociation appeared at larger scale in MMPOWER-3. A second study in older adults — an open-label single-arm phase 2a pilot in 30 participants, NCT07275424 — began recruiting in November 2025 and has posted no data.

The shape of the trial record

Twenty-nine registered studies span cardiology, nephrology, ophthalmology, neurology and rare mitochondrial disease, sponsored almost entirely by Stealth BioTherapeutics. The pattern across them is informative. Phase 2 trials in heart failure with reduced and with preserved ejection fraction, in acute heart failure with congestion, in reperfusion injury after percutaneous coronary intervention, and in renal artery stenosis were run between 2012 and 2017. The programme subsequently narrowed to rare mitochondrial disease and ophthalmology, and two mitochondrial myopathy studies were terminated.

Currently active work includes ReNEW, a phase 3 trial in dry age-related macular degeneration with 313 participants and primary completion in August 2027, and a phase 3b/4 confirmatory trial in Barth syndrome with 48 participants running to September 2029 — the latter reflecting the confirmatory obligation attached to the accelerated approval. NuPower, a phase 3 trial in primary mitochondrial disease from nuclear DNA mutations with 102 participants, completed in September 2024 and has not been published.

Two phase 1 studies of oral Bendavia in healthy volunteers were completed in 2013. Neither has published data, and all subsequent development used subcutaneous, intravenous or topical ophthalmic delivery.

What is not known

The largest and most rigorous test of this compound in its lead indication failed. MMPOWER-3 enrolled 218 participants and missed both co-primary endpoints, and the trial was subsequently terminated. This is the single most important fact about the compound's efficacy evidence and it is routinely omitted from summaries. The approval that exists is narrow and provisional: accelerated approval in Barth syndrome, an ultra-rare X-linked disorder, on the basis of knee extensor muscle strength as an intermediate endpoint, in patients weighing at least 30 kg, with a confirmatory phase 3b/4 trial not due to complete until September 2029. The Barth evidence base is small in absolute terms — 12 randomised participants, 8 reaching week 168 of the extension. The pattern visible across the trial record is a repeated dissociation between mitochondrial parameters that move and functional outcomes that do not: ATP capacity rose without fatigue resistance changing in healthy older adults; ellipsoid zone progression slowed without the visual acuity or geographic atrophy endpoints being met. Nothing is published on use in pregnancy or lactation. NuPower, the phase 3 trial in nuclear-DNA primary mitochondrial disease, completed in September 2024 and its data have not appeared. Long-term safety beyond the 168-week Barth extension in eight patients is uncharacterised.

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