SS-31 is a mitochondria-targeted tetrapeptide, also known as elamipretide and previously as MTP-131 and Bendavia. It localises to the inner mitochondrial membrane and binds cardiolipin, a phospholipid required for the formation of mitochondrial cristae.

What did the July 2026 meta-analysis find about elamipretide?

That it did not perform well. Pooled across six mitochondria-targeted agents in heart failure, the analysis found improvements in ejection fraction and NYHA class and reductions in mortality and hospitalisation. In the subgroup analysis the combined elamipretide and resveratrol arm was not associated with a significant ejection-fraction improvement compared with baseline, and the meta-regression ranked elamipretide the least effective of the agents evaluated.

How much elamipretide data was in that meta-analysis?

Two studies out of 31, totalling 107 patients: a 36-person phase 1 infusion study from 2017 and the 71-person PROGRESS-HF phase 2 trial from 2020. Coenzyme Q10 or ubiquinol contributed 13 studies and trimetazidine nine. The pooled mortality and hospitalisation signal rests on the coenzyme Q10 and ubiquinol arm: in the subgroup analysis neither trimetazidine nor L-carnitine reduced mortality significantly.

Has elamipretide ever met a randomised primary endpoint?

In the trials we reviewed, rarely. MMPOWER-1 in mitochondrial myopathy produced a positive exercise result in an early dose-escalation setting. PROGRESS-HF in heart failure, MMPOWER-2 and the pivotal phase 3 MMPOWER-3 in mitochondrial myopathy, the randomised part of TAZPOWER in Barth syndrome, EMBRACE STEMI in heart attack and ReCLAIM-2 in dry macular degeneration all missed their primary endpoints.

Is elamipretide approved anywhere?

Once. The FDA granted accelerated approval on 19 September 2025 under the brand name Forzinity, for improving muscle strength in adult and paediatric patients weighing at least 30 kg who have Barth syndrome, a genetic disorder affecting roughly 150 people in the United States. There is no EMA approval and no approval for any other condition.

What does accelerated approval mean here?

That the approval rests on an intermediate clinical endpoint, an improvement in knee extensor muscle strength, and is conditional. FDA required a randomised, double-blind, placebo-controlled confirmatory trial in patients aged five and older to verify the clinical benefit, with a final report due in March 2030, and the approval letter states that the approval can be withdrawn if that trial fails to verify benefit.

What happened at the FDA advisory committee?

Before the October 2024 meeting, FDA's own briefing document stated that the available evidence did not establish effectiveness for Barth syndrome, and the question put to the committee was whether elamipretide can be concluded effective on the available evidence. A majority of the committee voted yes. FDA still did not approve straight away: it issued an action letter on 15 May 2025, and accelerated approval followed in September 2025, after the company filed a complete response in August.

What did the phase 3 mitochondrial myopathy trial show?

MMPOWER-3 randomised 218 patients to 24 weeks of subcutaneous elamipretide or placebo and missed both primary endpoints: the six-minute walk distance differed by -3.2 metres (p = 0.69) and the fatigue score by -0.07 (p = 0.37). The registry lists the trial as terminated, with the stated reason that the double-blind portion did not meet its primary endpoints.

Why do some sources quote large improvements in Barth syndrome?

Because they come from the open-label extension rather than the randomised comparison. In the randomised part of TAZPOWER neither primary endpoint was met. The often-quoted 95.9 metre walk improvement and 2.1 point symptom improvement were measured at 36 weeks in the open-label extension, where everyone knew they were receiving the compound and there was no placebo group.

How solid is the cardiolipin mechanism?

The binding itself is well supported by in vitro work and animal models, beginning with a 2013 study that demonstrated high-affinity binding to cardiolipin and protection of cristae in a rat kidney ischemia model. The longer causal chain that usually follows in marketing copy, from binding to cristae stabilisation to reduced oxidative stress to more ATP, is extrapolation. The approved label states only that the compound binds cardiolipin, localises to the inner mitochondrial membrane and improves mitochondrial morphology and function.

Does SS-31 help heart failure?

Not on the randomised evidence available. The phase 2 PROGRESS-HF trial missed its primary endpoint at both doses and showed no ejection-fraction difference, the 2017 phase 1 study was designed to assess adverse events rather than efficacy, and the 2026 meta-analysis ranked elamipretide last among the six agents it evaluated. A third, larger phase 2 heart-failure trial with 308 patients completed in 2017 and appears never to have been published.

Is SS-31 the same as MOTS-c?

No. Both are discussed in the context of mitochondria, but MOTS-c is a 16 amino acid peptide encoded in mitochondrial DNA, while SS-31 is a synthetic four amino acid peptide that localises to the inner mitochondrial membrane. Their evidence bases are also very different: SS-31 has been through multiple randomised human trials, while FDA's own literature search in July 2026 found no published clinical studies of MOTS-c in human subjects.

What were the reported side effects in the trials?

The most consistently reported issue across the subcutaneous trials is injection-site reactions, described as occurring in about 80 percent of participants in one crossover trial and mostly mild. In the eye trial, adverse events occurred in 86 percent of the treated group against 71 percent on placebo. This is a summary of published trial safety reporting, not a safety assessment of any research material.

Why is the research-grade compound not the same as the approved product?

An approved medicine is manufactured to pharmaceutical standards, comes with a label, a defined indication and a regulated supply chain, and in this case exists in one country for one rare disease. A research compound is supplied for laboratory use and carries none of that. The existence of the approval says nothing about any research material, which is why identity and purity documentation matters independently.

How can the identity and purity of SS-31 be checked?

Through a batch-specific certificate of analysis from a third-party laboratory reporting identity, normally by mass spectrometry, purity by HPLC and the measured content per vial, verifiable against the issuing laboratory's records. Our supplier batch reports are published per batch on our CoA page.

Is SS-31 approved or sold as a medicine in the EU?

No. There is no EU marketing authorisation for elamipretide. We supply SS-31 as a research compound for laboratory use only, not for human consumption, and we give no dosing or usage recommendations.

SS-31 Ranked Last of Six: What 16 Years of Elamipretide Trials Actually Show (2026)

Important notice: This article summarises published clinical research and regulatory documents for scientific information only. SS-31 is supplied by us as a research compound, not for human consumption. The one approved elamipretide product discussed here is a prescription medicine authorised in the United States for a single ultra-rare disease, and its existence is not a statement about any other use. Nothing here is a dosing recommendation, a protocol or medical advice.

TL;DR: one of the very few peptides we sell with a real randomised trial record, and the most sobering one

New this month: a systematic review and meta-analysis of six mitochondria-targeted agents in heart failure, pooling 31 studies and 2,603 patients, published in Frontiers in Cardiovascular Medicine and PubMed-listed on 13 July 2026. It is the first meta-analysis to include elamipretide. The pooled result looks good: ejection fraction improved, more patients improved by at least one NYHA class, all-cause mortality was lower (risk ratio 0.62) and heart-failure hospitalisations fell (risk ratio 0.60). The part that concerns SS-31: elamipretide contributed 2 of the 31 studies, showed no significant ejection-fraction improvement, and the meta-regression ranked it the least effective of the agents evaluated. The mortality signal rests on the coenzyme Q10 and ubiquinol studies: in the subgroup analysis neither L-carnitine nor trimetazidine reduced mortality significantly. Zoomed out: elamipretide has failed the primary endpoint of a phase 3 mitochondrial myopathy trial, a phase 2 heart-failure trial, a phase 2a heart-attack trial and a phase 2 eye trial. It holds exactly one approval anywhere in the world: a US accelerated approval from September 2025 for Barth syndrome, a disease affecting roughly 150 people in the United States.

SS-31longevity

Mitochondria-targeted tetrapeptide (Elamipretide) that stabilizes cardiolipin and prevents ROS formation at the source.

Why this compound deserves an honest article

SS-31, also called elamipretide and previously MTP-131 or Bendavia, is unusual in our catalogue. Most research peptides have thin human evidence because almost nobody has run the trials. SS-31 is the opposite case: a company has spent more than a decade running real randomised trials of it, in several diseases, with pre-registered endpoints and published results.

That makes it one of the few compounds where you can ask a hard question and get a real answer. The answer is more complicated than either the marketing or the dismissals suggest.

The new meta-analysis, and what it actually shows

The June 2026 paper pooled 31 studies published between 1992 and 2023, comprising 24 randomised controlled trials and 7 crossover trials with 2,603 patients in total, across six mitochondria-targeted agents.

Agent	Studies contributed
Coenzyme Q10 or ubiquinol	13
Trimetazidine	9
Carnitine family	5
Elamipretide (SS-31)	2
Resveratrol	1
Cyclosporine	1

Coenzyme Q10 or ubiquinol

Studies contributed: 13

Trimetazidine

Studies contributed: 9

Carnitine family

Studies contributed: 5

Elamipretide (SS-31)

Studies contributed: 2

Resveratrol

Studies contributed: 1

Cyclosporine

Studies contributed: 1

Pooled across all six, the results are encouraging: ejection fraction improved against baseline (standardised mean difference 0.53, 95 percent confidence interval 0.42 to 0.65) and against controls (0.42, 0.31 to 0.53), more patients improved an NYHA functional class (risk ratio 2.38, 1.48 to 3.84, number needed to treat 3), all-cause mortality fell (risk ratio 0.62, 0.47 to 0.82, number needed to treat 23) and heart-failure hospitalisations fell (risk ratio 0.60, 0.42 to 0.85). Six-minute walking distance, notably, did not improve significantly against controls.

Read the subgroup, not the headline

The pooled result is not a result about SS-31. In the paper's own words, "elamipretide and resveratrol was not associated with a significant improvement in LVEF compared to baseline", while L-carnitine was, and in the meta-regression elamipretide ranked as the least effective of the agents evaluated. That subgroup estimate pools elamipretide together with resveratrol; for elamipretide on its own, the discussion is explicit that PROGRESS-HF showed no LVEF improvement against placebo or baseline, and that in the phase 1 study "there was no significant improvement in LVEF at any dose". The entire elamipretide contribution is two trials totalling 107 patients: a 36-person phase 1 infusion study and the 71-person PROGRESS-HF trial. If you take the mortality and hospitalisation benefit from this paper and attach it to SS-31, you have attached a coenzyme Q10 result to a peptide that the same analysis places last.

Quality caveats the authors state themselves

Nine of the 31 studies were judged low risk of bias, fifteen raised some concerns and seven were high risk. Most crossover trials were analysed as parallel-group trials because paired data were not reported, which prevents adjustment for within-subject correlation. Only about 13 percent of studies included heart failure with preserved ejection fraction. The abstract describes the certainty of evidence as low across all outcomes, although the paper's own GRADE table rates mortality moderate and two outcomes very low.

Every major elamipretide trial, including the ones that failed

This is the part that no product page will show you. These are the pre-registered, published, randomised trials.

Trial	Design	Primary endpoint	Result
Daubert 2017, heart failure	Phase 1, n = 36, single 4-hour infusion	Adverse events	Safety endpoint met. In the highest-dose group, end-diastolic volume fell 18 mL (p = 0.009) and end-systolic volume 14 mL (p = 0.005) at end of infusion.
PROGRESS-HF 2020, heart failure	Phase 2, n = 71, 4 or 40 mg daily for 28 days	Change in end-systolic volume	Not met. 4 mg versus placebo -0.3 (p = 0.90), 40 mg versus placebo +2.3 (p = 0.28). No ejection-fraction difference either.
MMPOWER-1 2018, mitochondrial myopathy	Phase 1/2, n = 36, ascending infusions	Exercise performance	Primary comparison missed at p = 0.053 (highest dose 64.5 m versus 20.4 m on placebo); significant only in a covariate-adjusted model (51.2 versus 3.0 m, p = 0.0297), with a dose-dependent increase (p = 0.014). Graded Class I evidence by the journal.
MMPOWER-2 2020, mitochondrial myopathy	Phase 2 crossover, n = 30, 4 weeks	Six-minute walk distance	Not met. Difference 19.8 m (p = 0.0833). Patient-reported fatigue scores did improve.
MMPOWER-3 2023, mitochondrial myopathy	Phase 3, n = 218, 24 weeks	Walk distance and fatigue	Not met, in both. Walk distance -3.2 m (p = 0.69), fatigue -0.07 (p = 0.37). Registered as terminated, with the reason given as the double-blind portion missing its endpoints.
TAZPOWER, Barth syndrome	Phase 2/3 crossover, n = 12	Walk distance and symptom score	Neither met in the randomised part. In the open-label extension at 36 weeks, walk distance improved 95.9 m (p = 0.024) and the symptom score 2.1 points (p = 0.031).
EMBRACE STEMI 2016, heart attack	Phase 2a randomised	Infarct size	Not met, and no improvement in imaging, angiographic, electrocardiographic or clinical outcomes.
ReCLAIM-2 2024, dry macular degeneration	Phase 2, n = 176, 48 weeks	Low-luminance vision and lesion area	Co-primary endpoints not met. Additional predefined imaging endpoints, reported with nominal p-values, showed reductions in progression.

Daubert 2017, heart failure

Design: Phase 1, n = 36, single 4-hour infusion
Primary endpoint: Adverse events
Result: Safety endpoint met. In the highest-dose group, end-diastolic volume fell 18 mL (p = 0.009) and end-systolic volume 14 mL (p = 0.005) at end of infusion.

PROGRESS-HF 2020, heart failure

Design: Phase 2, n = 71, 4 or 40 mg daily for 28 days
Primary endpoint: Change in end-systolic volume
Result: Not met. 4 mg versus placebo -0.3 (p = 0.90), 40 mg versus placebo +2.3 (p = 0.28). No ejection-fraction difference either.

MMPOWER-1 2018, mitochondrial myopathy

Design: Phase 1/2, n = 36, ascending infusions
Primary endpoint: Exercise performance
Result: Primary comparison missed at p = 0.053 (highest dose 64.5 m versus 20.4 m on placebo); significant only in a covariate-adjusted model (51.2 versus 3.0 m, p = 0.0297), with a dose-dependent increase (p = 0.014). Graded Class I evidence by the journal.

MMPOWER-2 2020, mitochondrial myopathy

Design: Phase 2 crossover, n = 30, 4 weeks
Primary endpoint: Six-minute walk distance
Result: Not met. Difference 19.8 m (p = 0.0833). Patient-reported fatigue scores did improve.

MMPOWER-3 2023, mitochondrial myopathy

Design: Phase 3, n = 218, 24 weeks
Primary endpoint: Walk distance and fatigue
Result: Not met, in both. Walk distance -3.2 m (p = 0.69), fatigue -0.07 (p = 0.37). Registered as terminated, with the reason given as the double-blind portion missing its endpoints.

TAZPOWER, Barth syndrome

Design: Phase 2/3 crossover, n = 12
Primary endpoint: Walk distance and symptom score
Result: Neither met in the randomised part. In the open-label extension at 36 weeks, walk distance improved 95.9 m (p = 0.024) and the symptom score 2.1 points (p = 0.031).

EMBRACE STEMI 2016, heart attack

Design: Phase 2a randomised
Primary endpoint: Infarct size
Result: Not met, and no improvement in imaging, angiographic, electrocardiographic or clinical outcomes.

ReCLAIM-2 2024, dry macular degeneration

Design: Phase 2, n = 176, 48 weeks
Primary endpoint: Low-luminance vision and lesion area
Result: Co-primary endpoints not met. Additional predefined imaging endpoints, reported with nominal p-values, showed reductions in progression.

Read down that column and the pattern is clear. Elamipretide has produced signals in early and open-label settings, and has repeatedly failed to confirm them in the randomised, blinded, adequately sized version of the same question. That is the most common way a promising compound fails, and it is exactly why phase 3 trials exist.

The one approval, and what it is for

On 19 September 2025 the FDA granted accelerated approval to elamipretide under the brand name Forzinity, for Barth syndrome, an ultra-rare genetic disorder affecting roughly 150 people in the United States. The indication is narrow: to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg.

The path there is instructive. The company submitted an application in August 2021 against FDA's advice and received a Refusal-to-File letter, with FDA stating that the application did not contain a single adequate and well-controlled trial that could establish effectiveness. Going into the October 2024 advisory committee meeting, FDA's written position was unchanged: it "does not believe that the available evidence establishes the effectiveness of elamipretide for the treatment of BTHS". A majority of the committee disagreed. Even then FDA did not approve: on 15 May 2025, seven months after the favourable vote, it issued an action letter, and the accelerated approval followed only after the company filed a complete response on 15 August 2025.

Accelerated approval means the question is still open

Accelerated approval here rests on what the label calls an improvement in knee extensor muscle strength, an intermediate clinical endpoint, and it comes with a debt. FDA required a randomised, double-blind, placebo-controlled confirmatory trial in Barth syndrome patients aged five and older "to verify and describe the clinical benefit". The agreed timetable runs to a final report in March 2030. The approval letter also spells out the consequence: if the confirmatory trial fails to verify clinical benefit, or is not conducted with due diligence, the approval can be withdrawn. There is no EMA approval, and the company's own materials note that there are no EMA-approved therapies for this condition.

What the mechanism claim rests on

SS-31 is described almost everywhere as binding cardiolipin, a phospholipid of the inner mitochondrial membrane, thereby stabilising cristae, reducing oxidative stress and increasing ATP production. The first half of that sentence is well supported. The second half is an extrapolation.

The foundational work, published in 2013, used a fluorescent analogue to show high-affinity binding to cardiolipin, showed that the complex inhibits cytochrome c peroxidase activity, and showed that pretreatment protected cristae membranes in a rat model of renal ischemia. That is an in vitro binding assay plus an animal model. A 2020 biophysical study refined the picture, proposing that the peptide partitions into the membrane interface and modulates surface electrostatics, and describing the mechanisms as nonexclusive rather than settled.

The most disciplined statement of the mechanism is the one FDA approved. Section 12.1 of the Forzinity label, in its entirety, reads: "FORZINITY is a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function." No ATP, no oxidative stress, no apoptosis. When a regulator writes the shortest possible version of a mechanism, that is usually a signal about how much of the longer version is established.

How to hold this compound in your head

Separate the target from the drug

Mitochondrial dysfunction is a real and well-evidenced feature of heart failure and of mitochondrial myopathies. That the target is real does not make any particular molecule aimed at it effective, and the new meta-analysis is a clean demonstration: the class shows benefit, the specific peptide ranks last within it.

Separate open-label from randomised

Almost every positive elamipretide number comes from an open-label extension, a dose-escalation cohort or a secondary endpoint. Almost every randomised, blinded primary endpoint has been missed. When you see a walk-distance improvement quoted, check which of the two it came from.

Separate one rare disease from everything else

The 2025 approval covers Barth syndrome in the United States, on an intermediate clinical endpoint, with a confirmatory trial still to report in 2030. It is not an approval for heart failure, for mitochondrial myopathy generally, for eye disease, or for healthy people interested in mitochondria.

What this means for research use

SS-31 remains a legitimate and interesting research compound: there is a plausible mechanism, real preclinical work behind it, and an unusual amount of human data for a peptide of this kind. What there is not, in 2026, is randomised evidence that it improves cardiac function, exercise capacity or fatigue in the populations where it has been tested most seriously. Anyone designing research with it is working in an area where the well-funded, well-run version of the same question has repeatedly come back negative, and that is worth knowing before rather than after. Our supplier batch reports for SS-31, from a third-party laboratory, are on our CoA page.

Related compounds

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The compound in this article

SS-31longevity

Mitochondria-targeted tetrapeptide (Elamipretide) that stabilizes cardiolipin and prevents ROS formation at the source.

Other mitochondrial and longevity research compounds

MOTS-clongevity

Mitochondrial-derived signaling peptide (16 amino acids) that mimics the effects of exercise at the cellular level. Activates AMPK, improves glucose uptake, and enhances fat metabolism - a key tool in metabolic and longevity research.

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Essential cellular coenzyme that declines with age. Powers energy metabolism in every cell, activates sirtuins (longevity genes), and supports DNA repair. A cornerstone molecule in aging and longevity research.

Epitalonlongevity

Tetrapeptide (Ala-Glu-Asp-Gly) that activates telomerase, the enzyme responsible for maintaining telomere length. One of the most studied peptides in longevity research, developed by Prof. Khavinson at the St. Petersburg Institute of Bioregulation.

FAQ

Sources

Mohammed O, Rasheed SA, Arora A, et al. "Therapeutic targeting of mitochondrial dysfunction in heart failure: a systematic review and meta-analysis of clinical outcomes." Frontiers in Cardiovascular Medicine 2026;13:1824101. PMID 42440741. https://pubmed.ncbi.nlm.nih.gov/42440741/
Daubert MA, et al. "Novel mitochondria-targeting peptide in heart failure treatment." Circulation: Heart Failure 2017. Phase 1 infusion study, n = 36. PMID 29217757. https://pubmed.ncbi.nlm.nih.gov/29217757/
Butler J, et al. PROGRESS-HF: phase 2 trial of elamipretide in heart failure with reduced ejection fraction, n = 71. PMID 32068002. https://pubmed.ncbi.nlm.nih.gov/32068002/
Karaa A, et al. MMPOWER-3: phase 3 trial of elamipretide in primary mitochondrial myopathy, n = 218, 24 weeks. PMID 37268435. https://pubmed.ncbi.nlm.nih.gov/37268435/
Reid Thompson W, et al. TAZPOWER: randomised crossover trial of elamipretide in Barth syndrome, n = 12, plus open-label extension. PMID 33077895. https://pubmed.ncbi.nlm.nih.gov/33077895/
Gibson CM, et al. "EMBRACE STEMI study: a phase 2a trial of intravenous MTP-131." European Heart Journal 2016;37(16):1296-1303. PMID 26586786. https://pubmed.ncbi.nlm.nih.gov/26586786/
US Food and Drug Administration. Forzinity (elamipretide) approval letter and prescribing information, 19 September 2025, application 215244, including the postmarketing requirement for a confirmatory randomised trial. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf
Birk AV, et al. "The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin." Journal of the American Society of Nephrology 2013;24(8):1250-1261. PMID 23813215. https://pubmed.ncbi.nlm.nih.gov/23813215/

Research disclaimer: All content serves scientific information only. SS-31 is supplied as a research compound, is not intended for human consumption and holds no EU marketing authorisation. Trial figures are reported as published study results, never as expectations for any other use.