SS-31
FDA ApprovedA first-in-class mitochondria-targeting tetrapeptide that binds cardiolipin on the inner mitochondrial membrane. Developed by Stealth BioTherapeutics for mitochondrial diseases, heart failure, and age-related macular degeneration. Phase 3 trials in primary mitochondrial myopathy did not meet primary endpoints, but Barth syndrome data was positive. Strong preclinical rationale with mixed clinical translation.
Elamipretide · Bendavia · MTP-131
12 human studies
- Preclinical
- 66%
- Clinical
- 34%
Based on 35 cited sources
clinically demonstrated · low confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 76: ≥2 independent RCTs (MMPOWER-3 PMM Phase 3 37268435, TAZPOWER Barth Phase 2/3 33077895, PROGRESS-HF Phase 2 32068002, EMBRACE STEMI Phase 2a 26586786, ReCLAIM AMD Phase 2) [1A 30], double-blind low-RoB RCTs but no high-confidence systematic review [1B 15], total human N 300–1,000 across trials [1C 9], direct population/route/outcome match [1D 13], extensive replicated preclinical program across rabbit/sheep/dog/mouse and human ex-vivo tissue [1E 9]. Mechanism 81: named target cardiolipin with binding + functional confirmation (Birk 23813215, Mitchell 32273339) [2A 30], full target→ETC→ROS/cristae pathway mapped [2B 26], in-vivo dose-response across models [2C 15], confirmed in-vivo mammalian [2D 10]. Plausibility 77: mechanism→surrogate (respiration, LVEF) solid but surrogate→clinical partial since several Phase 3 primaries missed [3A 28], fully coherent with cardiolipin/Barth biology [3B 24], class analogy from MitoQ with mixed translation [3C 14], moderately broad multi-organ scope [3D 11]. Global Coverage 79: replicated across multiple independent groups/countries [4A 27], many countries (US/EU/China/Korea) [4B 22], ~35 cited / >100 total PubMed studies [4C 20], FDA-approved single regulator [4D 10]. Community Experience 46: niche persistent longevity-circle use [5A 10], ~3–7yr track record [5B 17], thin but consistent reports [5C 10], no recurring adverse signal over limited exposure [5D 9]. Effectiveness basis clinical (low confidence): Barth OLE ~96m 6MWT gain (33077895) and ReCLAIM low-luminance visual-acuity benefit exceed MCID and are patient-relevant, but controlled Phase 3 primaries (PMM, HFrEF) were missed and positive signals derive largely from uncontrolled open-label extensions/subgroups; first approved therapy for Barth with no prior standard of care.
The mechanisms of SS-31 have been well-characterized in preclinical and mechanistic studies. Unlike conventional antioxidants, SS-31 targets the source of reactive oxygen species rather than scavenging them after formation.
How It Works (Simplified)
SS-31 is a mitochondria-targeting peptide that optimizes cellular energy production:
Rapidly penetrates cells and concentrates 1,000-5,000x inside mitochondria within minutes, specifically localizing to the inner membrane.
Binds to cardiolipin, a unique phospholipid essential for respiratory complex function, optimizing its interactions with cytochrome c.
Improves electron transport chain efficiency - more ATP produced per oxygen consumed, fewer electrons leak to form damaging superoxide.
Protects cardiolipin from peroxidation, maintains cristae structure, and stabilizes membrane potential to prevent cell death cascades.
Key Research: Birk AV et al. (2013) elucidated the cardiolipin binding mechanism. PMID:23813215
FDA Approval & Clinical Milestones
SS-31 (elamipretide) received FDA approval in September 2025 under the brand name Forzinity for the treatment of Barth syndrome, making it the first mitochondria-targeted peptide therapeutic to achieve regulatory approval. The approval was supported by the TAZPOWER clinical program (NCT03098797), including open-label extension data through 168 weeks demonstrating sustained functional improvements.
NuPower Therapeutics (formerly Stealth BioTherapeutics) continues Phase 3 development for additional mitochondrial conditions beyond Barth syndrome.
Important Limitations
- Phase 3 trials in PMM did not meet primary endpoints despite strong preclinical data
- Clinical translation has been challenging due to heterogeneous patient populations
- Functional endpoints (6MWT) may not capture mitochondrial-specific improvements
- Optimal patient selection biomarkers still being identified
- Human pharmacokinetics differ from plasma half-life due to tissue concentration
| NCT ID | Title | Peptide | Phase | Status | Completion |
|---|---|---|---|---|---|
| NCT02805790 | TAZPOWER: Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Myopathy Primary Mitochondrial Disease | SS-31 | Phase 2 | Completed | Mar 2017 |
| NCT03323749 | SPIMM-301: Subcutaneous Elamipretide in Primary Mitochondrial Myopathy Primary Mitochondrial Myopathy | SS-31 | Phase 3 | Terminated | Feb 2020 |
| NCT02367014 | TAZPOWER-Barth: Elamipretide in Barth Syndrome Mitochondrial Myopathy | SS-31 | Phase 1/2 | Completed | Apr 2016 |
| NCT03891875 | ReCLAIM-2: Elamipretide in Geographic Atrophy Secondary to Dry AMD Age-related Macular Degeneration | SS-31 | Phase 2 | Completed | Feb 2022 |
| NCT03098797 | ReCLAIM: Elamipretide Topline in Dry AMD Barth Syndrome | SS-31 | Phase 2/3 | Completed | Oct 2018 |
| NCT02814097 | PROGRESS-HF: Elamipretide in Heart Failure With Reduced Ejection Fraction Chronic Heart Failure | SS-31 | Phase 2 | Completed | May 2017 |
| NCT02388464 | EMBRACE STEMI: Elamipretide in ST-Elevation Myocardial Infarction Congestive Heart Failure | SS-31 | Phase 1 | Completed | Apr 2015 |
| NCT02245620 | Phase 1/2 Dose-Escalation Study in Primary Mitochondrial Myopathy Skeletal Muscle Mitochondrial Dysfunction in the Elderly | SS-31 | Phase 2 | Completed | Jul 2016 |
| NCT02693119 | Elamipretide in Renal Artery Stenosis (EVREST) Leber's Hereditary Optic Neuropathy | SS-31 | Phase 2 | Completed | Sep 2019 |
| NCT02914665 | Elamipretide in Leber's Hereditary Optic Neuropathy (LHON) Heart Failure | SS-31 | Phase 2 | Completed | Nov 2017 |
| NCT07531251 | Clinical Trial in Patients With Barth Syndrome- 4TAZPower Barth Syndrome | SS-31 | Phase 4 | Not yet recruiting | Sep 2029 |
| NCT07275424 | Study of Healthy Aging and Physical Function With Elamipretide Aging, Healthy | SS-31 | Phase 2 | Recruiting | Mar 2026 |
| NCT06373731 | ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD) Age Related Macular Degeneration (ARMD) | SS-31 | Phase 3 | Active | Aug 2027 |
| NCT05162768 | Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD) Mitochondrial Myopathies, Mitochondrial Pathology +6 more | SS-31 | Phase 3 | Completed | Sep 2024 |
| NCT05168774 | FRDA Investigator Initiated Study (IIS) With Elamipretide Friedreich Ataxia | SS-31 | Phase 1/2 | Completed | Jun 2024 |
| NCT02976038 | Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM) Primary Mitochondrial Disease | SS-31 | Phase 2 | Terminated | Mar 2020 |
| NCT02848313 | An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration Age-Related Macular Degeneration | SS-31 | Phase 1 | Completed | Mar 2018 |
| NCT02788747 | Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction Heart Failure | SS-31 | Phase 2 | Completed | Sep 2017 |
| NCT02653391 | A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED) Fuchs' Corneal Endothelial Dystrophy (FCED) | SS-31 | Phase 1/2 | Completed | Mar 2018 |
| NCT02388529 | A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Bendavia™ (MTP-131) in Patients With Heart Failure Heart Failure | SS-31 | Phase 1 | Withdrawn | Sep 2015 |
| NCT02436447 | A Phase 1 Study Investigating the Safety and Pharmacokinetics of Repeat-dose Intravenous Infusion of MTP-131 in Subjects With Impaired Renal Function Normal and Impaired Renal Function | SS-31 | Phase 1 | Completed | Jul 2015 |
| NCT02314299 | A Study of MTP-131 Topical Ophthalmic Solution in Subjects With Diabetic Macular Edema and Non-Exudative Intermediate Age-related Macular Degeneration Diabetic Macular Edema, Age-related Macular Degeneration | SS-31 | Phase 1/2 | Completed | May 2015 |
| NCT01786915 | Safety and Pharmacokinetic (PK) Study of Oral Bendavia Administered for 7 Days Healthy Volunteers | SS-31 | Phase 1 | Completed | Mar 2013 |
| NCT01755858 | Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery Renal Artery Obstruction, Hypertension, Renovascular +1 more | SS-31 | Phase 1/2 | Terminated | Dec 2015 |
| NCT01754818 | A Phase 1 Study Examining the Pharmacokinetics and Tolerability of a Single Oral Dose of Bendavia (MTP-131) Healthy | SS-31 | Phase 1 | Completed | Jan 2013 |
| NCT01572909 | Evaluation of Myocardial Effects of MTP-131 for Reducing Reperfusion Injury in Patients With Acute Coronary Events Reperfusion Injury, STEMI | SS-31 | Phase 2 | Completed | Nov 2014 |
| NCT01518985 | The Impact of Intravenous Bendavia™ on Endothelial Reactivity Dysfunction in Cigarette Smoking Healthy Volunteers | SS-31 | Phase 1 | Completed | Mar 2012 |
| NCT01513200 | Study to Assess the Pharmacodynamic Effects of Unfractionated Heparin (UFH) in Healthy Volunteers With and Without Bendavia Healthy Volunteers | SS-31 | Phase 1 | Completed | Feb 2012 |
| NCT01115920 | Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of Intravenous (IV) Infusion of MTP-131 (Bendavia™) in Healthy Adults Healthy | SS-31 | Phase 1 | Completed | Sep 2010 |
TAZPOWER: Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Myopathy
SPIMM-301: Subcutaneous Elamipretide in Primary Mitochondrial Myopathy
ReCLAIM-2: Elamipretide in Geographic Atrophy Secondary to Dry AMD
PROGRESS-HF: Elamipretide in Heart Failure With Reduced Ejection Fraction
EMBRACE STEMI: Elamipretide in ST-Elevation Myocardial Infarction
Phase 1/2 Dose-Escalation Study in Primary Mitochondrial Myopathy
Elamipretide in Leber's Hereditary Optic Neuropathy (LHON)
Clinical Trial in Patients With Barth Syndrome- 4TAZPower
Study of Healthy Aging and Physical Function With Elamipretide
ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD)
Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)
FRDA Investigator Initiated Study (IIS) With Elamipretide
Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)
An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration
Effect of Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Reduced Ejection Fraction
A Study Investigating the Safety, Tolerability, and Efficacy of Elamipretide Topical Ophthalmic Solution for the Treatment of Fuchs' Corneal Endothelial Dystrophy (FCED)
A Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of Bendavia™ (MTP-131) in Patients With Heart Failure
A Phase 1 Study Investigating the Safety and Pharmacokinetics of Repeat-dose Intravenous Infusion of MTP-131 in Subjects With Impaired Renal Function
A Study of MTP-131 Topical Ophthalmic Solution in Subjects With Diabetic Macular Edema and Non-Exudative Intermediate Age-related Macular Degeneration
Safety and Pharmacokinetic (PK) Study of Oral Bendavia Administered for 7 Days
Effects of Intravenous Bendavia™ on Reperfusion Injury in Patients Undergoing Angioplasty of the Renal Artery
A Phase 1 Study Examining the Pharmacokinetics and Tolerability of a Single Oral Dose of Bendavia (MTP-131)
Evaluation of Myocardial Effects of MTP-131 for Reducing Reperfusion Injury in Patients With Acute Coronary Events
The Impact of Intravenous Bendavia™ on Endothelial Reactivity Dysfunction in Cigarette Smoking
Study to Assess the Pharmacodynamic Effects of Unfractionated Heparin (UFH) in Healthy Volunteers With and Without Bendavia
Study to Evaluate Safety, Tolerability, and Pharmacokinetics (PK) of Intravenous (IV) Infusion of MTP-131 (Bendavia™) in Healthy Adults
SS-31 rapidly crosses plasma membrane and concentrates 1000-5000x in mitochondria. Binds cardiolipin on inner mitochondrial membrane. In aged mice, single 1-hour treatment showed immediate improvements in mitochondrial function.
PMID:23692570Clinical trials used daily SC dosing with steady state achieved within days. The PROGRESS-HF Phase 2 trial dosed daily for 28 days but did not significantly change cardiac structural parameters versus placebo.
PMID:32068002Phase 3 PMM trials evaluated 24-week endpoints. In the Barth syndrome TAZPOWER trial, significant 6-minute walk and symptom improvements emerged during the open-label extension by 36 weeks. Long-term extension studies showed durable improvements in completers.
PMID:33077895168-week open-label extension data in Barth syndrome suggests sustained effects. The ongoing Phase 3 ReNEW trial in dry AMD is evaluating chronic dosing for geographic atrophy. Long-term human pharmacokinetics and optimal treatment duration continue to be characterized.
PMID:38602181Research-based observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Good Signs (7 indicators)
Warning Signs (5 indicators)
Bad Signs (7 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Mitoq
CompatibleDifferent mitochondrial targets - SS-31 binds cardiolipin on inner membrane while MitoQ accumulates in matrix. May provide complementary antioxidant and bioenergetic effects. No interaction studies available.
Coq10
CompatibleCoQ10 functions as electron carrier in ETC while SS-31 optimizes cardiolipin-cytochrome c interactions. Theoretically complementary mechanisms for mitochondrial support.
Nad-Precursors
CompatibleNAD+ precursors (NMN, NR) support different aspects of mitochondrial function than SS-31. Non-overlapping mechanisms may provide additive benefits.
Urolithin-A
CompatibleUrolithin A promotes mitophagy while SS-31 optimizes existing mitochondrial function. Different but potentially complementary approaches to mitochondrial health.
Idebenone
CompatibleIdebenone bypasses Complex I while SS-31 optimizes overall ETC efficiency through cardiolipin. May have additive effects in mitochondrial dysfunction.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
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