Peptide Evidence Index

SS-31 (Elamipretide)

Evidence last reviewed: September 2026

Quick answers

What is it?: SS-31, known clinically as elamipretide, is a synthetic four-amino-acid peptide designed to concentrate inside the inner mitochondrial membrane and bind cardiolipin, a lipid mitochondria need to produce energy.
Why are people interested in it?: It has one of the most extensive human trial programs of any peptide in this library, spanning four different diseases over more than a decade, which makes its results unusually easy to check.
What has actually been studied?: Randomized, double-blind, placebo-controlled Phase 1-3 trials in Barth syndrome, primary mitochondrial myopathy, heart failure, and dry age-related macular degeneration.
How strong is the evidence?: Genuinely mixed: every completed Phase 2 or 3 program has missed or only partly met its primary endpoint, though several show positive results in open-label extensions or subgroups.
What don't we know yet?: Why open-label results and subgroups look better than blinded comparisons, and whether any trial will succeed clearly enough to support approval, are both unresolved.
Where can I read the original research?: Sources at the bottom of this page: Thompson et al., Genetics in Medicine 2020; Karaa et al., Orphanet Journal of Rare Diseases 2024.

Plain-English overview

SS-31 -- its clinical name is elamipretide -- is a synthetic peptide only four amino acids long, designed to concentrate in the inner mitochondrial membrane and bind cardiolipin, a lipid mitochondria need to produce energy efficiently. Developed by Stealth BioTherapeutics, it has been tested in more than two dozen human trials across Barth syndrome, primary mitochondrial myopathy, heart failure, and dry age-related macular degeneration over more than a decade. It has never been approved as a medicine anywhere. Its record is genuinely mixed: core randomized, blinded comparisons have repeatedly missed their primary endpoints, while open-label extensions, secondary measures, or specific patient subgroups have sometimes shown real improvement, keeping several development programs alive.

What researchers are studying it for

Barth syndrome
primary mitochondrial myopathy
heart failure (reduced and preserved ejection fraction)
dry age-related macular degeneration / geographic atrophy
Leber's hereditary optic neuropathy
ischemia-reperfusion injury during angioplasty

Current evidence level

Mixed human evidence

Regulatory status: Not an approved medicine. Evidence strength and approval are scored separately; approval is a regulatory decision about a specific use, not a measure of how much research exists.

Human research

In Barth syndrome, a rare genetic disease of heart and skeletal muscle, the randomized, double-blind, placebo-controlled crossover phase of the TAZPOWER trial (n=12) did not meet either primary endpoint -- a six-minute walk test or a fatigue symptom score (Thompson et al., 2020, Genetics in Medicine). In the subsequent open-label extension, in which all remaining participants knowingly received the drug, walk-test distance improved by a cumulative 96.1 meters by week 168 (P=.003), and fatigue scores and some cardiac measures also improved (Thompson et al., 2024, Genetics in Medicine). In primary mitochondrial myopathy, the Phase 3 MMPOWER-3 trial (n=218) did not demonstrate a significant overall benefit in its genotypically diverse population; a post hoc analysis found a subgroup with nuclear-DNA-related mitochondrial disease trended toward improved walking distance, now being tested in a dedicated follow-up trial (Karaa et al., 2024, Orphanet Journal of Rare Diseases). In heart failure with reduced ejection fraction, a 71-patient Phase 2 trial (PROGRESS-HF) found no significant improvement in heart chamber volumes on cardiac MRI at either tested dose compared with placebo (Butler et al., 2020, Journal of Cardiac Failure). An earlier, smaller first-in-heart-failure study (n=36) had found a significant reduction in left ventricular volume, but only at the highest single-infusion dose (Daubert et al., 2017, Circulation: Heart Failure). In dry age-related macular degeneration, the 176-patient Phase 2 ReCLAIM-2 trial did not meet its primary visual-acuity and geographic-atrophy-growth endpoints, but did show a significant slowing of ellipsoid-zone loss, a structural marker of photoreceptor damage, which is now the primary endpoint for an ongoing Phase 3 trial (Ehlers et al., 2024, Ophthalmology Science).

Animal and preclinical research

The material reviewed for this entry does not describe a distinct animal-only literature separate from SS-31's extensive human trial program; nearly all of its development has proceeded directly through human Phase 1-3 studies, and no specific preclinical study was detailed in the sources reviewed.

Major findings

The core, blinded phase of the Barth syndrome trial (TAZPOWER, n=12) met neither primary endpoint, but its open-label extension showed a 96.1-meter cumulative improvement in six-minute walk distance by week 168 (P=.003) (Thompson et al., 2020 & 2024).
The largest and most definitive mitochondrial myopathy trial (MMPOWER-3, n=218) did not show significant overall benefit; a subgroup with nuclear-DNA-related disease trended toward improvement, prompting a dedicated follow-up trial (Karaa et al., 2024).
A 71-patient heart failure trial (PROGRESS-HF) found no significant improvement in ventricular volumes at either dose tested (Butler et al., 2020).
An earlier, smaller heart-failure study found a significant ventricular-volume reduction, but only at the single highest infusion dose (Daubert et al., 2017).
The 176-patient ReCLAIM-2 dry-AMD trial missed its primary visual and structural endpoints but found a significant slowing of photoreceptor-layer loss, now used as the primary endpoint in an ongoing Phase 3 trial (Ehlers et al., 2024).
Across nearly every recent trial, the same 40 mg once-daily subcutaneous dose was used regardless of condition, and dose was not the factor separating positive from negative results.

What has not been established

Why open-label extensions and small subgroups repeatedly show improvement that core randomized comparisons do not.
Whether the nuclear-DNA-mutation subgroup signal in mitochondrial myopathy will hold up in its dedicated follow-up Phase 3 trial.
Whether the structural eye-imaging benefit in dry AMD will translate into a vision benefit patients can perceive.
What happens with use beyond the roughly one-to-three-year windows tested so far.
Whether elamipretide will succeed clearly enough in any large blinded trial to support regulatory approval.

Important limitations

Every completed Phase 2 or 3 program to date has missed or only partly met its primary efficacy endpoint.
Positive results have come mainly from open-label extensions (no placebo comparison) or post hoc subgroup analyses, both weaker forms of evidence than a blinded primary result.
Trial populations were small for a genetic and rare-disease focus (n=12 to n=218 in the trials described here).
All trials ran under close clinical monitoring in people with a specific, often rare, diagnosed disease, not healthy volunteers.

Regulatory status

SS-31/elamipretide is not approved as a medicine anywhere. Every completed Phase 2 or Phase 3 program to date has either missed its primary endpoint or produced mixed results. Development is ongoing, including an active Phase 3 dry-AMD trial (ReNEW) built around the ellipsoid-zone endpoint identified in ReCLAIM-2.

Primary research sources

Thompson WR, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER): Genet Med 2020;23(3):471-478. PMID: 33077895
Thompson WR, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER: Genet Med 2024;26(7):101138. PMID: 38602181
Karaa A, et al. Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial: Orphanet J Rare Dis 2024;19(1):431. PMID: 39574155
Butler J, et al. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial: J Card Fail 2020;26(5):429-437. PMID: 32068002
Daubert MA, et al. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide: Circ Heart Fail 2017;10(12). PMID: 29217757
Ehlers JP, et al. ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration: Ophthalmol Sci 2024;5(1):100628. PMID: 39605874

Full evidence entry (complete data, registry records, dosing evidence)

Mixed human evidence

Controlled human trials exist and disagree

At a glance

Also known as: Elamipretide, MTP-131, Bendavia (early research name), SS-31
Class: Synthetic aromatic-cationic tetrapeptide, mitochondria-targeting agent
Derived from: A synthetic four-amino-acid peptide from the Szeto-Schiller (SS) peptide series, designed to concentrate in the inner mitochondrial membrane and bind cardiolipin, a lipid essential to mitochondrial energy production
Registered human trials: 21
…with published results: Most of the 21 registered trials are completed with posted results or full publications, spanning Barth syndrome, primary mitochondrial myopathy, heart failure, and macular degeneration
Largest human trial: 308 patients hospitalized with heart failure and congestion (Phase 2, 2016-2017)
Studied for: Barth syndrome, primary mitochondrial myopathy, heart failure (reduced and preserved ejection fraction), dry age-related macular degeneration / geographic atrophy, Leber's hereditary optic neuropathy, ischemia-reperfusion injury during angioplasty
Dosing evidence: Doses used in trialsNearly every human trial has used the same daily 40 mg subcutaneous dose regardless of condition, but that dose has repeatedly failed to separate from placebo on the trials' primary efficacy endpoints; no dose of elamipretide has been shown reliably effective for any condition.
Regulatory status: Not approved as a medicine anywhere. Every completed Phase 2 or Phase 3 program to date has either missed its primary endpoint or produced mixed results. Development is ongoing (a Phase 3 dry-AMD trial, ReNEW, is active), and an expanded-access program exists for some patients with genetically confirmed mitochondrial disease.

What it is

SS-31 — its clinical name is elamipretide — is a small synthetic peptide, only four amino acids long, designed to concentrate inside the inner mitochondrial membrane and bind cardiolipin, a lipid mitochondria need to produce energy efficiently. The idea is that stabilizing this lipid could help failing mitochondria work better, in diseases where energy production at the cellular level is thought to be part of the problem.

It has never been approved as a medicine anywhere, despite more than a decade of clinical development by its manufacturer, Stealth BioTherapeutics, across several different diseases.

What the studies actually found

Elamipretide has a genuinely extensive trial record, and the results are a real mixture — some clearly negative, some clearly positive only in open-label or exploratory analyses, and at least one indication still being pursued into Phase 3.

In Barth syndrome, a rare genetic disease affecting heart and skeletal muscle, the core randomized, double-blind, placebo-controlled phase of the TAZPOWER trial did not meet either of its co-primary endpoints — a walking-distance test and a fatigue symptom score — in its 12 participants (Thompson et al., 2020, Genetics in Medicine). The subsequent open-label extension, in which everyone knew they were receiving the drug, did show statistically significant improvement from the start of that extension, sustained out to 168 weeks (Thompson et al., 2024, Genetics in Medicine). An open-label result without a placebo comparison is weaker evidence than a blinded one.

In primary mitochondrial myopathy, the Phase 3 MMPOWER-3 trial — the largest and most definitive study of this use — did not demonstrate a significant overall benefit, according to the trial's own investigators. A post hoc subgroup of patients with a specific class of nuclear-DNA-related mitochondrial disease showed a trend toward improved walking distance, which is now being tested in a dedicated follow-up Phase 3 trial (Karaa et al., 2024, Orphanet Journal of Rare Diseases).

In heart failure, a Phase 2 trial in patients with reduced ejection fraction found no significant improvement in heart chamber volumes on cardiac MRI at either tested dose, compared with placebo (Butler et al., 2020, Journal of Cardiac Failure) — though an earlier, smaller first-in-heart-failure study had found a significant reduction in ventricular volume at its highest single-infusion dose (Daubert et al., 2017, Circulation: Heart Failure).

In dry age-related macular degeneration, the Phase 2 ReCLAIM-2 trial did not meet its primary visual-acuity and geographic-atrophy-growth endpoints in 176 patients, but did show a significant slowing of a structural marker of photoreceptor loss — a result now being used as the primary endpoint for an ongoing Phase 3 trial (Ehlers et al., 2024, Ophthalmology Science).

What exists in humans

Twenty-one trials are registered on ClinicalTrials.gov, nearly all sponsored by Stealth BioTherapeutics, spanning Barth syndrome, primary mitochondrial myopathy, heart failure, dry AMD, Leber's hereditary optic neuropathy, Fuchs' corneal dystrophy, and ischemia-reperfusion injury during coronary or renal artery procedures. Most are completed, and most have posted results or a full publication — this is one of the more thoroughly documented compounds in this library, which is precisely what makes its repeated primary-endpoint misses notable rather than a case of "no one ever checked."

What doses have been studied in humans

Across nearly every recent human trial — Barth syndrome, mitochondrial myopathy, and the geographic atrophy and Fuchs'-dystrophy eye trials — researchers used the same 40 mg once-daily subcutaneous injection, typically for 12 weeks to just under a year, compared with a matching placebo. Earlier heart failure and reperfusion-injury studies instead tested intravenous infusions at several different rates over a few hours to 28 days.

Despite this consistency, dose was not the limiting factor in most negative results — the same 40 mg daily dose was used in trials that failed their primary endpoint and in trials whose secondary or open-label results looked more favorable. An administered amount is well documented for this compound, but it has not translated reliably into a proven clinical benefit for any single condition tested so far.

None of this dosing evidence applies to any unsupervised or off-label use, since every trial ran under close clinical monitoring, mostly in people with a specific, often rare, diagnosed disease.

What remains unknown

Why open-label extensions and small subgroups repeatedly show improvement that the core randomized

comparisons do not

Whether the nuclear-DNA-mutation subgroup signal in mitochondrial myopathy will hold up in the

dedicated Phase 3 trial built around it

Whether the structural eye-imaging benefit seen in dry AMD will translate into a vision benefit

patients can perceive

What happens with use beyond the roughly one-to-three-year windows tested so far
Whether any future trial will succeed clearly enough, in a large enough blinded comparison, to

support regulatory approval

Registry and study records

A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER core): PubMed · Thompson et al., 2020, Genetics in Medicine. 'In part 1 neither primary endpoint was met.' DOI: 10.1038/s41436-020-01006-8
Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER: PubMed · Thompson et al., 2024, Genetics in Medicine. Unblinded extension; 96.1 m cumulative 6MWT improvement at week 168, P=.003. DOI: 10.1016/j.gim.2024.101138
Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial: PubMed · Karaa et al., 2024, Orphanet Journal of Rare Diseases. 'The MMPOWER-3 clinical trial did not demonstrate a significant benefit... in a genotypically diverse population.' DOI: 10.1186/s13023-024-03421-5
Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial: PubMed · Butler et al., 2020, Journal of Cardiac Failure. n=71; no significant improvement in LVESV at either dose. DOI: 10.1016/j.cardfail.2020.02.001
Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide: PubMed · Daubert et al., 2017, Circulation: Heart Failure. n=36; significant LV volume reduction at highest single-infusion dose only. DOI: 10.1161/CIRCHEARTFAILURE.117.004389
ReCLAIM-2: A Randomized Phase II Clinical Trial Evaluating Elamipretide in Age-related Macular Degeneration: PubMed · Ehlers et al., 2024, Ophthalmology Science. n=176; primary endpoints not met; exploratory ellipsoid-zone endpoint positive. DOI: 10.1016/j.xops.2024.100628
TAZPOWER (Barth syndrome): ClinicalTrials.gov NCT03098797 · Phase 2/3, n=12, completed 2021
MMPOWER-3 (primary mitochondrial myopathy): ClinicalTrials.gov NCT03323749 · Phase 3, n=218, completed 2020
Elamipretide in heart failure hospitalized with congestion: ClinicalTrials.gov NCT02914665 · Phase 2, n=308, completed 2017
ReCLAIM-2 (dry AMD, noncentral geographic atrophy): ClinicalTrials.gov NCT03891875 · Phase 2, n=176, completed 2022

See the full Evidence Index →

Evidence last reviewed: September 2026. Peptide Proof reports what studies found. We do not give medical advice, dosing guidance, or treatment recommendations.