Ss 31: Safety Profile & Research Summary
17 PubMed CitationsExpert ReviewedGMP CertifiedLast Reviewed: April 2026
Preclinical & Clinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Sabbah et al. (2016) | Dogs, microembolization HF β 0.5 mg/kg SC Γ 3 mo | LVEF 30%β36% (p<0.05); NT-proBNP β774 pg/mL (p<0.001); ATP/ADP 1.16 vs 0.38 control | [6] |
| Dai et al. (2013) | C57BL/6 mice TAC β osmotic minipump Γ 4 wk | Fibrosis reduced ~5% vs ~15% control (p=0.005); protected 84% of mitochondrial proteins | [14] |
| Campbell et al. (2019) | 26-mo female C57BL/6 mice β 3 mg/kg/day SC Γ 8 wk | Treadmill endurance nearly doubled (p<0.05); reversed ATPmax decline; no β mitochondrial content | [4] |
| Chiao et al. (2020) | Aged C57BL/6 mice β cardiac dysfunction model | Late-life SS-31 administration reversed age-related cardiac dysfunction; restored diastolic function | [15] |
| Zhao et al. (2019) | LPS cognitive impairment mice β 5 mg/kg IP | Escape latency β (p<0.01); hippocampal TNF-Ξ±/IL-6 β (p<0.05); BDNF signaling enhanced | [8] |
| Birk et al. (2013) | Ischemic renal tubules β 1 nMβ1 Β΅M in vitro; rodent ARAS model | Re-energized ischemic mitochondria; restored tubular ATP; protected brush border membranes | [11] |
| 26-wk Rat Tox (FDA NDA) | Sprague Dawley rats β SC 5β15 mg/kg/day Γ 26 wk | Systemic NOAEL 40/15 mg/kg/day (~6.2-fold human AUC); primary AEs: injection site only; no systemic toxicity | [3] |
| 39-wk Dog Tox (FDA NDA) | Beagles β SC 2.5β20 mg/kg/day Γ 39 wk | Systemic NOAEL 20/10 mg/kg/day (~5.7-fold human AUC); no ECG/BP/HR effects up to 100 mg/kg | [3] |
Clinical Trials Summary
| Trial | Indication | n / Design | Key Outcome | Ref |
|---|---|---|---|---|
| TAZPOWER P2/3 OLE (NCT03098797) | Barth syndrome | n=12; 40 mg SC daily; 168-wk OLE | +96.1 m 6MWT (p=0.003); β muscle strength; β LV stroke volume β basis for FDA approval | [9] |
| MMPOWER Phase 1/2 (NCT02367014) | Primary mitochondrial myopathy | n=36; IV 0.25 mg/kg/h Γ 5 days | +64.5 m 6MWT vs +20.4 m placebo (p=0.053); significant dose-dependent effect (p=0.014) | [10] |
| MMPOWER-3 Phase 3 (NCT03323749) | Primary mitochondrial myopathy | n=218; 40 mg SC daily Γ 24 wk | Failed primary (6MWT -3.2 m, p=0.69); post-hoc benefit in nDNA replisome mutation subgroup | [10] |
| EMBRACE-STEMI Ph2a (NCT01572909) | Acute MI (ischemia) | n=118; IV 0.05 mg/kg/h | No significant infarct size reduction; trend toward reduced CHF events | [16] |
| PROGRESS-HF Phase 2 | Heart failure (HFrEF) | n=71; 4 or 40 mg SC Γ 28 days | No significant LVESV improvement vs placebo | [5] |
| ARAS Phase 2a (NCT01755858) | Renal artery stenosis | n=14; IV 0.05 mg/kg/h during angioplasty | Renal blood flow 262 vs 202 mL/min (p=0.04); improved GFR | [13] |
| ReCLAIM-2 Phase 2 (NCT03891875) | Dry AMD | 40 mg SC daily | Failed primary (VA, GA area); slowed ellipsoid zone degradation | [12] |
| ReNEW Phase 3 (NCT06373731) | Dry AMD | n=360 target; 40 mg SC Γ 96 wk | Ongoing (2026) | [12] |
Safety Summary
| Parameter | Finding |
|---|---|
| Most common AEs | Injection site reactions (erythema, pruritus, pain β up to 80% in some studies), headache, dizziness, fatigue |
| Cardiovascular | No significant changes in BP, HR, or QTc across all clinical trials |
| Serious AEs | Rare: 1 hypersensitivity reaction in PMM trial |
| Genotoxicity | Negative in Ames, chromosomal aberration, and in vivo micronucleus assays |
| Reproductive toxicity | No teratogenicity in rats or rabbits at clinically relevant exposures |
| Special populations | Contains benzyl alcohol β contraindicated in neonates (gasping syndrome risk). Post-marketing MATE1 inhibition study required (metformin interaction) |
| Drug interactions | Not CYP450 substrate; potential MATE1 inhibition (metformin); no known QT-prolonging interactions |
| Concentrations used | In vitro: 1 nMβ1 Β΅M effective range. In vivo: 1β5 mg/kg/day (mice); 0.5 mg/kg/day (dogs); 40 mg SC daily (humans, approved dose) |
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References
- Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology. 2014;171(8):2029-2050.
- Birk AV, Liu S, Soong Y, 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.
- FDA Press Announcement. FDA approves first treatment for rare genetic heart muscle disease. September 19, 2025.
- Campbell MD, Duan J, Bhatt SK, et al. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radical Biology and Medicine. 2019;134:268-281.
- Sabbah HN. Elamipretide (SS-31) improves mitochondrial function and prevents cellular apoptosis in heart failure and its comorbidities. Expert Opinion on Investigational Drugs. 2021;30(12):1227-1244.
- Sabbah HN, Gupta RC, Kohli S, et al. Chronic therapy with elamipretide (MTP-131), a novel mitochondria-targeting peptide, improves left ventricular and mitochondrial function in dogs with advanced heart failure. Circulation: Heart Failure. 2016;9(2):e002206.
- Sabbah HN, Klewer SE, O'Brien T, et al. Elamipretide and NF-ΞΊB/NLRP3 inflammasome inhibition. Biomedicine & Pharmacotherapy. 2025;183:118056.
- Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic integrity, and cognition in an Alzheimer's disease model. Scientific Reports. 2019;9(1):13137.
- Thompson WR, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genetics in Medicine. 2024;101138.
- Karaa A, Haas R, Goldstein A, et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018;90(14):e1212-e1221.
- Birk AV, Chao WM, Bracken C, et al. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. British Journal of Pharmacology. 2014;171(8):2017-2028.
- Cousins D, Brar P, McFarlane T, et al. Phase 2 study of elamipretide (SS-31) in age-related macular degeneration (ReCLAIM-2). Ophthalmology Retina. 2023.
- Saad A, Herrmann SMS, Eirin A, et al. Phase 2a clinical trial of mitochondrial protection (elamipretide) during stent revascularization in patients with atherosclerotic renal artery stenosis. Circulation: Cardiovascular Interventions. 2017;10(9):e005130.
- Dai DF, Hsieh EJ, Chen T, et al. Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Circulation: Heart Failure. 2013;6(5):1067-1076.
- Chiao YA, Rabinovitch PS, Bhatt SK, et al. Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice. eLife. 2020;9:e55513.
- Lincoff AM, Bhatt DL, Fischell T, et al. Elamipretide and postβcardiac arrest outcomes (EMBRACE STEMI). American Heart Journal. 2014;168(2):222-228.
- FDA Integrated Review NDA 215244 β Forzinity (elamipretide) Approval Package. 2025.
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This content is provided for educational and informational purposes only. Products are furnished for in-vitro studies only and are not medicines, drugs, or supplements. Not approved by the FDA to prevent, treat, or cure any condition.