SS-31 (elamipretide) peptide: the trials behind the 2025 approval, the trials that missed, and what the gray-market use rests on

At a glance

What SS-31 is, and why it is also called elamipretide and Forzinity

SS-31 is a peptide in the mitochondrial peptides class (cardiolipin-binding, inner-membrane targeted). Europe PMC indexes 493 publications naming it or a listed alias in a title or abstract, including 16 randomized controlled trials and 14 clinical trials of any design, as of 14 Sep 2026. The strongest evidence tier in that literature is human clinical trials.

This page reports what those studies state, sentence by sentence, with each statement tied to its source and labeled by the kind of evidence it is. It does not recommend use, and it does not translate study doses into anything personal.

• SS-31 is elamipretide, a four-amino-acid synthetic peptide (D-arginine, dimethyltyrosine, lysine, phenylalanine) from the Szeto-Schiller series designed at Cornell in the early 2000s. Its alternating positive and aromatic residues let it cross cell membranes and concentrate a thousandfold in the inner mitochondrial membrane, where it binds cardiolipin, the lipid that holds the respiratory-chain complexes in their working arrangement and that is abnormal in Barth syndrome.Editorial synthesis
  Editorial synthesis from general knowledge
• The proposed effect is structural rather than chemical: by binding cardiolipin it is thought to stabilise cristae, keep cytochrome c in its electron-carrying role rather than its peroxidase role, and so raise ATP output while lowering the reactive oxygen produced by a leaking chain. Early papers called it an antioxidant; the developers' later work describes it as a cardiolipin-protective compound, and the older-adult trial is the human demonstration: ATP capacity up within hours of one infusion, then back to baseline.Editorial synthesis
  Editorial synthesis from general knowledge
• What is not established is durable benefit outside cardiolipin disorders. The mechanism predicts the largest effect where cardiolipin is most abnormal, which is Barth syndrome, and the trial record matches: the Barth programme produced the approval, while the genotypically mixed myopathy trial, the heart-failure trial and the eye trials did not meet their primary endpoints.Editorial synthesis
  Editorial synthesis from general knowledge

• Randomized controlled trial humans 2024 Human clinical trial
  Doses stated in the abstract: 40 mg
  Patients entering the OLE continued elamipretide 40 mg subcutaneous daily.
  Source pmid-38602181 · quoted verbatim from the abstract, emphasis added
• Randomized controlled trial humans n = 218 2023 Human clinical trial
  Doses stated in the abstract: 40 mg/d
  After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously.
  Source pmid-37268435 · quoted verbatim from the abstract, emphasis added
• Phase 3 clinical trial humans n = 8 2022 Human clinical trial
  Doses stated in the abstract: 40 mg daily
  A phase 3, observational, retrospective, and non-interventional study was designed to establish a natural history control (NHC) cohort of patients with Barth syndrome (BTHS) to provide further analysis of the efficacy of elamipretide observed in an open-label extension (OLE) phase of the TAZPOWER trial, a clinical trial that tested the efficacy of 40 mg daily of elamipretide in patients with BTHS.
  Source pmid-36056411 · quoted verbatim from the abstract, emphasis added
• Randomized controlled trial humans n = 12 2021 Human clinical trial
  Doses stated in the abstract: 40 mg per day
  In part 1, 12 subjects were randomized to 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm.
  Source pmid-33077895 · quoted verbatim from the abstract, emphasis added
• Randomized controlled trial humans n = 30 2020 Human clinical trial
  Doses stated in the abstract: 40 mg/day
  Participants were randomly assigned (1:1) to 40 mg/day SC elamipretide for 4 weeks followed by placebo SC for 4 weeks, separated by a 4-week washout period, or the opposite sequence.
  Source pmid-32096613 · quoted verbatim from the abstract, emphasis added
• Case report humans 2025 Observational, human
  Doses stated in the abstract: 0.25 mg/kg; 0.5 mg/kg
  On day of life (DOL) 34, therapy with daily IV elamipretide (0.25 mg/kg increased to 0.5 mg/kg on DOL39) began, followed by standard-of-care oral heart failure medications.
  Source pmid-39917770 · quoted verbatim from the abstract, emphasis added

• Randomized controlled trial humans 2024 Human clinical trial
  Elamipretide was well tolerated, with injection-site reactions being the most common adverse events.
  Source pmid-38602181 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 12 2024 Human clinical trial
  The primary outcome measure was assessment of adverse events (AEs) from the administration of topical elamipretide, and the primary efficacy end point was change in best-corrected visual acuity (BCVA).
  Source pmid-37923251 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 218 2023 Human clinical trial
  Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity.
  Source pmid-37268435 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 30 2020 Human clinical trial
  Injection site reactions were the most commonly reported adverse events with elamipretide (80%), the majority of which were mild.
  Source pmid-32096613 · quoted verbatim from the abstract
• Human study humans 2024 Observational, human
  Elamipretide was well tolerated and both patients demonstrated improvement in symptoms while on therapy.
  Source pmid-39619320 · quoted verbatim from the abstract
• Trials that did not reach the ledger: PROGRESS-HF (2020) gave elamipretide to people with heart failure for 28 days and found no change in left-ventricular volume, its primary endpoint; ReCLAIM-2 tested it in dry age-related macular degeneration and, by the sponsor's report, missed its primary endpoints. Neither reported a safety signal beyond injection-site reactions. They are cited here from public summaries and are pending sources.Editorial synthesis
  Editorial synthesis from general knowledge · primary document to be added to the ledger
• No trial has given elamipretide to healthy people for longer than a single infusion, so the safety of months of use for energy or longevity is unmeasured. The disease trials ran up to 168 weeks in Barth syndrome (eight patients) and 24 weeks in 109 people with mitochondrial myopathy.Editorial synthesis
  Editorial synthesis from general knowledge

• Randomized controlled trial humans n = 218 2023 Human clinical trial
  Between the participants receiving elamipretide and those receiving placebo, the difference in the least squares mean (SE) from baseline to week 24 on distance walked on the 6MWT was -3.2 (95% CI -18.7 to 12.3; p = 0.69) meters, and on the PMMSA, the total fatigue score was -0.07 (95% CI -0.10 to 0.26; p = 0.37).
  Source pmid-37268435 · quoted verbatim from the abstract
• Phase 3 clinical trial humans n = 8 2022 Human clinical trial
  For the 6-min walk test (6MWT, primary endpoint), the least squares (LS) mean difference between groups was 79.7 m (P = 0.0004) at week 64 and 91.0 m (P = 0.0005) at week 76 in favor of elamipretide.
  Source pmid-36056411 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 19 2019 Human clinical trial
  Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3-2220.1) pg/mL vs. 496.5 (379.4-703.8) pg/mL ( P ⩽0.05).
  Source pmid-28534645 · quoted verbatim from the abstract
• Animal study mice 2026 Animal, preclinical
  In contrast, SS-31 reduced oocyte aneuploidy, ROS accumulation and DNA damage.
  Source pmid-41612464 · quoted verbatim from the abstract
• Animal study mice 2026 Animal, preclinical
  We therefore tested whether elamipretide, a synthetic cardiolipin-binding peptide, could improve mitochondrial function and cardiolipin levels in βTFP-deficient mice and patient-derived fibroblasts.
  Source pmid-41500837 · quoted verbatim from the abstract
• Animal study rats, mice 2026 Animal, preclinical
  In vitro experiments were performed on BV2 cells subjected to oxygen-glucose deprivation/reoxygenation, assessing cell viability, lipid peroxidation, ferroptosis-associated protein expression, and cytokine secretion following SS-31 intervention.
  Source pmid-41136322 · quoted verbatim from the abstract

• Animal study mice 2026 Animal, preclinical
  Co-administration of SS-31 and NMN significantly attenuated post-ischemic brain damage and ameliorated neurological deficits (P < 0.0001), demonstrating effects markedly superior to either monotherapy.
  Source pmid-42443448 · quoted verbatim from the abstract

• A single two-hour infusion raised muscle mitochondrial ATP capacity immediately; by day 7 the effect had gone, which the authors attributed to the drug's short half-life in human blood.Human clinical trial
  Source pmid-34264994
• In the dose-finding trial, walking distance rose within five days of treatment.Human clinical trial
  Source pmid-29500292
• In Barth syndrome, neither primary endpoint moved in 12 weeks of randomized treatment; at 36 weeks of open-label treatment walking distance had improved by 95.9 metres.Human clinical trial
  Source pmid-33077895

• Randomized controlled trial humans n = 36 2018 Human clinical trial
  Participants were randomized to intravenous elamipretide (0.01, 0.1, and 0.25 mg/kg/h or placebo for 2 hours in a dose-escalating sequence).
  Source pmid-29500292 · quoted verbatim from the abstract

• Randomized controlled trial humans 2024 Human clinical trial
  Durations stated: 28 week; 168 week
  TAZPOWER was a 28-week randomized, double-blind, and placebo-controlled trial followed by a 168-week OLE.
  Source pmid-38602181 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 12 2024 Human clinical trial
  Durations stated: 52 week; 52 weeks
  This phase II, prospective, randomized, vehicle-controlled, single-center clinical trial involved administration of elamipretide 1% topical ophthalmic solution to patients with LHON over a 52-week double-masked treatment period, followed by an open-label extension (OLE) for up to 108 additional weeks of treatment.
  Source pmid-37923251 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 218 2023 Human clinical trial
  Durations stated: 24 weeks
  After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously.
  Source pmid-37268435 · quoted verbatim from the abstract, emphasis added
• Clinical trial humans 2023 Human clinical trial
  Durations stated: 12 years
  In clinical trials, elamipretide produced clinical and functional improvements in adults and adolescents with mitochondrial disorders, such as primary mitochondrial myopathy and Barth syndrome; however, experience in younger patients is limited and to our knowledge, these are the first case reports on the safety and efficacy of elamipretide treatment in children under 12 years of age.
  Source pmid-36636586 · quoted verbatim from the abstract, emphasis added
• Randomized controlled trial humans n = 12 2021 Human clinical trial
  Durations stated: 12 weeks; 4 week
  In part 1, 12 subjects were randomized to 40 mg per day of elamipretide or placebo for 12 weeks, followed by a 4-week washout and then 12 weeks on the opposite arm.
  Source pmid-33077895 · quoted verbatim from the abstract, emphasis added
• Randomized controlled trial humans n = 30 2020 Human clinical trial
  Durations stated: 4 weeks; 4 week; 6 month
  Participants were randomly assigned (1:1) to 40 mg/day SC elamipretide for 4 weeks followed by placebo SC for 4 weeks, separated by a 4-week washout period, or the opposite sequence.
  Source pmid-32096613 · quoted verbatim from the abstract, emphasis added

• Randomized controlled trial humans n = 12 2025 Human clinical trial
  administration by subcutaneous route reported
  The BTHS-SA was administered in TAZPOWER, a phase 2, randomized, double-blind, placebo-controlled crossover study to evaluate daily subcutaneous injections of elamipretide in subjects with genetically confirmed BTHS.
  Source pmid-40281531 · quoted verbatim from the abstract
• Randomized controlled trial humans 2024 Human clinical trial
  administration by subcutaneous route reported
  Patients entering the OLE continued elamipretide 40 mg subcutaneous daily.
  Source pmid-38602181 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 12 2024 Human clinical trial
  administration by topical route reported
  This study aimed to assess the safety, tolerability, and potential efficacy of topical elamipretide in patients affected with Leber hereditary optic neuropathy (LHON).
  Source pmid-37923251 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 218 2023 Human clinical trial
  administration by subcutaneous route reported
  After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously.
  Source pmid-37268435 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 30 2020 Human clinical trial
  administration by subcutaneous route reported
  This study aims to evaluate the effect of subcutaneous (SC) elamipretide dosing on exercise performance using the 6 min walk test (6MWT), patient-reported outcomes measuring fatigue, functional assessments, and safety to guide the development of the Phase 3 trial.
  Source pmid-32096613 · quoted verbatim from the abstract
• Randomized controlled trial humans n = 36 2018 Human clinical trial
  administration by intravenous route reported
  Participants were randomized to intravenous elamipretide (0.01, 0.1, and 0.25 mg/kg/h or placebo for 2 hours in a dose-escalating sequence).
  Source pmid-29500292 · quoted verbatim from the abstract

• Case report humans 2025 Observational, human
  Weight-normalized doses as published: 0.25 mg/kg; 0.5 mg/kg
  On day of life (DOL) 34, therapy with daily IV elamipretide (0.25 mg/kg increased to 0.5 mg/kg on DOL39) began, followed by standard-of-care oral heart failure medications.
  Source pmid-39917770 · quoted verbatim from the abstract, emphasis added

• Outside the clinic, SS-31 circulates for energy, longevity, recovery and 'mitochondrial health', injected subcutaneously from research-chemical vials, often alongside MOTS-c or NAD+ precursors. Reported effects are more stamina and less brain fog; reported complaints are injection-site redness and, at higher amounts, nausea and dizziness. None of this comes from a study of that use. The nearest trial gave 39 healthy older adults one infusion and found a transient rise in muscle ATP capacity and no change in fatigue resistance. The doses on vendor pages were not derived from the trials, whose dose was 40 mg once daily under the skin, and are not reproduced here.Editorial synthesis
  Editorial synthesis from general knowledge

• Randomized controlled trial humans n = 218 2023 Human clinical trial
  After screening, eligible participants were randomized 1:1 to receive either 24 weeks of elamipretide at a dose of 40 mg/d or placebo subcutaneously.
  Source pmid-37268435 · quoted verbatim from the abstract

• An approved prescription medicine in the United States since 19 September 2025: Forzinity (elamipretide hydrochloride), granted accelerated approval to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg, supplied as 280 mg in 3.5 mL (80 mg/mL) for once-daily subcutaneous injection. Accelerated approval means the sponsor must confirm clinical benefit in a further study. It is not approved for primary mitochondrial myopathy, heart failure, dry macular degeneration or optic neuropathy, all of which were tried. Not approved in the EU. Vials sold as 'SS-31 peptide' are unapproved products containing the same molecule. The compound is not named on the WADA Prohibited List; the live list should be checked. The prescribing information is not yet in the ledger.Editorial synthesis
  Editorial synthesis from general knowledge · primary document to be added to the ledger

• The Forzinity prescribing information, the PROGRESS-HF heart-failure trial and the ReCLAIM-2 macular-degeneration trial are cited from public summaries and are not yet in the ledger.
• No trial has given elamipretide to healthy people for longer than a single infusion.
• The confirmatory study required by the accelerated approval has not reported.

Questions people ask

1. 1
   Mitochondrial Stress Commitment as an ARCH-Governed Biological Decision:Cardiolipin as the Ancestral Φ Substrate

   doi-10-20944-preprints202607-2136-v1 · 29 Jul 2026 · preprint
2. 2
   Elamipretide (SS-31) and Nicotinamide Mononucleotide (NMN) Combination Therapy Targets TREM2 to Mitigate Post-ischemic Brain Injury in Mice.

   pmid-42443448 · 14 Jul 2026 · peer-reviewed
3. 3
   Mitochondrial-targeted therapy with elamipretide preserves cardiac function and prevents late mortality in murine polymicrobial sepsis

   doi-10-64898-2026-07-03-736409 · 9 Jul 2026 · preprint
4. 4
   Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.

   pmid-42450582 · 28 Jun 2026 · peer-reviewed
5. 5
   SS-31 improves the quality of maternally aged oocytes by ameliorating mitochondrial function and metabolism.

   pmid-41612464 · 29 Jan 2026 · peer-reviewed
6. 6
   Elamipretide Improves Mitochondrial Function in Mitochondrial Trifunctional Protein-Deficient Mice and Human Fibroblasts.

   pmid-41500837 · 1 Jan 2026 · peer-reviewed
7. 7
   Endothelial Glycocalyx Degradation as a Mediator of Neuroinflammation and Cognitive Impairment in Aged Rats: Protective Role of SS-31.

   pmid-41247543 · 17 Nov 2025 · peer-reviewed
8. 8
   SS-31 improves post-cardiac arrest brain injury by inhibiting microglial ferroptosis and polarization.

   pmid-41136322 · 24 Oct 2025 · peer-reviewed
9. 9
   Mitochondrial-Targeted Protective Potential of Elamipretide for the In Vitro Production of Porcine Embryos.

   pmid-40941292 · 25 Aug 2025 · peer-reviewed
10. 10
    SS-31 Targets NOS2 to Enhance Osteogenic Differentiation in Aged BMSCs by Restoring Mitochondrial Function.

    pmid-40570323 · 26 Jun 2025 · peer-reviewed
11. 11
    Initial Psychometric Evaluation of the Barth Syndrome Symptom Assessment (BTHS-SA) for Adolescents and Adults in a Phase 2 Clinical Study.

    pmid-40281531 · 25 Apr 2025 · peer-reviewed
12. 12
    Expanded-access use of elamipretide in a newborn with Barth syndrome: a case report.

    pmid-39917770 · 22 Jan 2025 · peer-reviewed

Reference card

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1. 2026-09-29 · Reviewed by Adam Mirando, PharmD, on 2026-09-29.
2. 2026-09-24 · Written under the sequencing rule after research/intents/ss-31.json: guide (8 sections incl. a trial-by-trial table), FAQ to 12 plus 10 from the map, mechanism, reported-use, regulatory (Forzinity approval 2025-09-19, pending_source for the label) and timeline claims; evidence tier set to approved-label by hand; three misdrafted interactions claims removed; intent-driven H1 and title. Triage: ChEMBL approval fields set by hand so the fact tiles agree with the tier; two directory links added.
3. 2026-09-14 · Claims drafted extractively from 32 ledger sources by scripts/draft_claims.py: 42 claims, 25 evidence-table rows. Status researched -> draft.
4. 2026-09-14 · Claims drafted extractively from 32 ledger sources by scripts/draft_claims.py: 45 claims, 25 evidence-table rows. Status researched -> draft.
5. 2026-09-14 · Evidence fetched from Europe PMC and ChEMBL by scripts/fetch_evidence.py; claims not yet written.