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Research review · Sources checked October 17, 2026

SS-31 (elamipretide): what the research shows

SS-31 (elamipretide, also called MTP-131 or Bendavia) is a four-amino-acid peptide that binds cardiolipin in the inner mitochondrial membrane. It is FDA-approved only as Forzinity, under accelerated approval, to improve muscle strength in Barth syndrome patients weighing at least 30 kg, at 40 mg a day under the skin.[1][3]

What the animal research shows

In very old mice, a single 3 mg/kg injection restored muscle energy output to young levels within an hour, and 8 weeks of daily dosing improved exercise tolerance.[4][5]

Human data

A 2021 trial in 39 older adults found a borderline rise in one hand muscle’s ATP output after a single infusion (P = 0.055 on the raw change), gone by day 7.[6] Across 13 placebo-controlled phase 2 or 3 trials in heart, kidney, muscle and eye disease, none clearly met its main goal, including a 218-person phase 3 in mitochondrial myopathy and a 176-person trial in dry macular degeneration.[7][8][9] FDA’s clinical and statistical reviewers recommended against approval for Barth syndrome; the office director approved it, accepting more uncertainty for a disease affecting about 150 Americans.[2]

Safety

Injection-site reactions occurred in every Barth patient on the drug in the randomized trial. The label warns of hypersensitivity reactions, eosinophilia, benzyl alcohol in the formulation and a metformin transporter interaction, and notes that carcinogenicity studies have not been done.[1][3]

What is not known

No trial has tested SS-31 for aging. The only registered aging study is a 30-person open-label safety study.[10] A phase 3 in dry macular degeneration reads out in the second half of 2027.[11] For the full paper trail, see our teardown below.

References

  1. FDA. FORZINITY (elamipretide) injection, for subcutaneous use. Prescribing information, NDA 215244, revised 9/2025 (indication “to improve muscle strength” in Barth syndrome patients ≥30 kg, approved under accelerated approval on knee extensor strength; 40 mg once daily, 20 mg if eGFR <30; contains benzyl alcohol 20 mg/mL; hypersensitivity incl. serious reactions “minutes to months” after starting; injection-site reactions in 12 of 12 patients on drug vs 8 of 12 on placebo, erythema 100% vs 25%; eosinophilia peaking ~90 days; overdose signs “likely to be histamine-related”; no patients ≥65 in Barth studies; “Carcinogenicity studies have not been conducted”; MATE1 inhibitor; “not superior to placebo” on the randomized trial’s primary endpoints; knee strength gains “were not observed during the randomized trial but were observed during the extension period”; Table 3 median change in knee extensor strength at week 12: placebo −5 N, elamipretide +4 N; open-label week 168 +63 N in 8 patients). https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215244s000lbl.pdf. Checked October 17, 2026.
  2. FDA. Integrated Review, NDA 215244, Forzinity (elamipretide), Reference ID 5592071 (“The clinical and biostatistical reviewers and the Cross-Discipline Team Leader (CDTL) conclude that there is not substantial evidence of effectiveness on knee muscle strength for accelerated approval and recommend a Complete Response action”; elamipretide “does not directly target the underlying genetic defect that causes BTHS, nor does it meaningfully impact the elevated cardiolipin ratio”; the signatory authority “agrees that there is more uncertainty than we would accept for more common diseases” but approves for a disease of “~150 subjects in the United States”; refuse-to-file October 18, 2021; expanded-access case of a 20-year-old woman whom ambulance staff “treated … as anaphylactic shock” with adrenaline, classified by FDA as a serious allergic reaction; histamine release from rat mast cells above 49 µM, with rat blood levels below that threshold). https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/215244Orig1s000IntegratedR.pdf. Checked October 17, 2026.
  3. FDA. NDA 215244 accelerated approval letter for Forzinity, signed September 19, 2025 (postmarketing requirements: 4802-1 confirmatory randomized trial, completion 09/2029, final report 03/2030; 4802-2 26-week TgRasH2 mouse carcinogenicity study; 4802-3 2-year rat carcinogenicity study, completion 10/2029, report 01/2030; 4802-4 metformin interaction study; rare pediatric disease priority review voucher). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2025/215244Orig1s000ltr.pdf. Checked October 17, 2026.
  4. Siegel MP, Kruse SE, Percival JM, et al. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging Cell. 2013;12(5):763-771. doi:10.1111/acel.12102. PMID 23692570 (27-month-old mice, single 3 mg/kg injection into the belly; muscle energetics restored “to young levels … after only one hour”; no effect in young mice; 8 days of treatment raised endurance). https://pubmed.ncbi.nlm.nih.gov/23692570/. Checked October 17, 2026.
  5. Campbell MD, Duan J, Samuelson AT, et al. Improving mitochondrial function with SS-31 reverses age-related redox stress and improves exercise tolerance in aged mice. Free Radic Biol Med. 2019;134:268-281. doi:10.1016/j.freeradbiomed.2018.12.031. PMID 30597195 (26-month-old female mice, 3 mg/kg/day for 8 weeks). https://pubmed.ncbi.nlm.nih.gov/30597195/. Checked October 17, 2026.
  6. Roshanravan B, Liu SZ, Ali AS, et al. In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial. PLoS One. 2021;16(7):e0253849. doi:10.1371/journal.pone.0253849. PMID 34264994; PMC8282018; NCT02245620 (120 screened; 47 excluded for high mitochondrial function; 39 randomized; one 2-hour IV infusion at 0.25 mg/kg/h; first dorsal interosseous hand muscle; change in ATPmax P = 0.055, percent change P = 0.045, mean increase 27% vs 12%; no difference at day 7; no effect on fatigue resistance; funded by Stealth BioTherapeutics; authors report consulting payments from Stealth). https://pmc.ncbi.nlm.nih.gov/articles/PMC8282018/. Checked October 17, 2026.
  7. Jabbit analysis. SS-31 / elamipretide trials, FDA listings and PubMed counts, October 17, 2026: 30 ClinicalTrials.gov records that give the drug; 13 placebo-controlled phase 2 or 3 trials with an efficacy primary endpoint, hand-reviewed; FDA NDC bulk-ingredient and establishment-registration files dated October 16, 2026; PubMed counts. Data: https://jabbitapp.com/research/sources/ss31-elamipretide-trials-listings-2026-10-17.json. Script: ops/scripts/ss31_analysis.py. Checked October 17, 2026.
  8. Karaa A, Bertini E, Carelli V, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology. 2023;101(3):e238-e252. doi:10.1212/WNL.0000000000207402. PMID 37268435; NCT03323749 (218 patients; 6-minute walk −3.2 m vs placebo, P = 0.69; fatigue P = 0.37). https://pubmed.ncbi.nlm.nih.gov/37268435/. Checked October 17, 2026.
  9. Ehlers JP, Hu A, Boyer D, et al. ReCLAIM-2: a randomized phase II clinical trial evaluating elamipretide in age-related macular degeneration, geographic atrophy growth, visual function, and ellipsoid zone preservation. Ophthalmol Sci. 2025;5(1):100628 (published online October 2024). doi:10.1016/j.xops.2024.100628. PMID 39605874; NCT03891875 (176 patients aged ≥55; 40 mg a day for 48 weeks; “did not meet statistical significance for the primary end points”; 43% and 47% less progression of ellipsoid-zone loss, nominal P = 0.0034 and 0.0040). https://pubmed.ncbi.nlm.nih.gov/39605874/. ClinicalTrials.gov results: deaths 2 of 117 vs 0 of 59; serious adverse events 18 of 117 vs 6 of 59. https://clinicaltrials.gov/study/NCT03891875. Checked October 17, 2026.
  10. ClinicalTrials.gov. NCT07275424: Study of Healthy Aging and Physical Function With Elamipretide (SHAPE), University of Washington (30 adults aged 65–80; open-label, one arm, no placebo; primary outcome safety and tolerability of daily injections; eligibility includes “No known allergies/adverse effects from Fexofenadine”). https://clinicaltrials.gov/study/NCT07275424. Checked October 17, 2026.
  11. ClinicalTrials.gov. NCT06373731: ReNEW, phase 3 study of subcutaneous elamipretide in dry AMD (313 enrolled; primary outcome photoreceptor-loss growth at week 48). https://clinicaltrials.gov/study/NCT06373731. NCT07531251: 4TAZPower, Barth syndrome (48 planned; randomized, placebo-controlled). https://clinicaltrials.gov/study/NCT07531251. Checked October 17, 2026.

This page summarizes published research and regulatory documents. It is not medical advice and does not recommend using, sourcing, or dosing any of these substances.