SS-31, now called elamipretide, is a small synthetic peptide of four amino acids that enters cells and concentrates on the inner membrane of mitochondria, the cell’s energy-producing compartments. It binds cardiolipin, a phospholipid (a type of fat molecule) that the inner membrane needs to keep its folded shape and run the machinery that makes ATP. The “SS” stands for Szeto–Schiller, after the researchers who designed it. It was developed further by Stealth BioTherapeutics and has also been tested under the codes MTP-131 and Bendavia.
On September 19, 2025, the FDA granted elamipretide (brand name Forzinity) accelerated approval for one ultra-rare disease: Barth syndrome, an inherited cardiolipin disorder. The approval rests on a gain in knee muscle strength seen in an open-label extension of 10 patients. The randomized part of the same trial, and a large phase 3 trial in mitochondrial myopathy, missed their primary endpoints. No trial has tested it as a performance or recovery aid in healthy people.
This page summarizes what the FDA label, the FDA review and clinical trials report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Mitochondrial cardiolipin binder; synthetic tetrapeptide |
| Other names | SS-31, MTP-131, Bendavia; brand Forzinity (Stealth BioTherapeutics) |
| US approval | NDA 215244, accelerated approval September 19, 2025 (orphan drug, priority review) |
| Approved use | To improve muscle strength in Barth syndrome, patients weighing at least 30 kg |
| Route and strength | Subcutaneous injection; 280 mg/3.5 mL (80 mg/mL) single-patient-use vial |
| Labeled dose | 40 mg once daily; 20 mg once daily if eGFR under 30 mL/min and not on dialysis |
| Half-life (FDA review) | About 3–4 h; 3.2 h in healthy volunteers and 1.5 h in Barth syndrome patients after one 40 mg dose |
| Elimination | Broken down to inactive fragments; about 100% of a dose recovered in urine within 48 h |
| WADA status | Not named on the 2026 Prohibited List |
What it is
Elamipretide is a four-residue peptide with an amidated end. Its design alternates aromatic (ring-containing) and positively charged amino acids. It includes one D-amino acid, D-arginine, which resists breakdown by enzymes, and a non-natural, dimethylated form of tyrosine. The label lists the free peptide’s formula as C₃₂H₄₉N₉O₅; the marketed hydrochloride salt has a molecular weight of 749.2 (FDA label; PubChem).
The compound came out of opioid-peptide research at Weill Cornell. Szeto’s group noticed that a highly polar opioid tetrapeptide they were studying acted on the brain after injection under the skin, suggesting it crossed biological barriers, and then designed analogs such as SS-31 that keep this property but have negligible affinity for opioid receptors (Szeto and Birk, Clin Pharmacol Ther 2014). In cell and isolated-mitochondria experiments, these peptides concentrated about 1,000-fold in the inner mitochondrial membrane and reduced oxidative damage (Zhao et al., J Biol Chem 2004).
The mechanism was later refined. Rather than acting mainly as a general antioxidant, SS-31 binds cardiolipin with high affinity. In rats with kidney ischemia, pretreatment protected the cristae (the inner-membrane folds) and sped ATP recovery after blood flow returned (Birk et al., J Am Soc Nephrol 2013). The FDA label describes the mechanism in one line: it localizes to the inner mitochondrial membrane and “improves mitochondrial morphology and function.”
It is not a hormone, a growth-hormone secretagogue or an anabolic agent. It does not act on androgen, growth hormone or IGF-1 pathways. Related mitochondria-focused peptides in this library include MOTS-c and humanin, which act by different mechanisms.
Pharmacokinetics
From the FDA label and the FDA integrated review (FDA label; FDA integrated review):
| Parameter | Value |
|---|---|
| Time to peak after subcutaneous dose | 0.5–1 h |
| Bioavailability (subcutaneous) | About 92% |
| Volume of distribution | About 0.5 L/kg (total body water) |
| Plasma protein binding | About 39% |
| Half-life, single 40 mg dose | 3.16 h in healthy volunteers (n = 32); 1.48 h in Barth syndrome patients (n = 7) |
| Half-life at steady state, 40 mg daily for 7 days | 2.8 h (n = 5) |
| Accumulation with daily dosing | Minimal (ratio 1.03) |
| Metabolism | Stepwise trimming from the C-terminal end to an inactive tripeptide (M1) and dipeptide (M2); no liver metabolism seen in vitro |
| Excretion | Urine; about 100% of a dose recovered within 48 h |
Peak levels after a 40 mg dose averaged about 1,710 ng/mL in healthy volunteers and 1,852 ng/mL in Barth patients. Exposure rises in proportion to dose over 2–80 mg.
Because the kidneys clear it, exposure rises with kidney impairment. Elamipretide AUC (total exposure) rose by 39%, 75% and 125% in mild, moderate and severe impairment. The inactive metabolites M1 and M2 rose up to 280% and 640% in severe impairment, which is why the label halves the dose when eGFR is under 30 mL/min.
Approved medical use
Barth syndrome
Barth syndrome is an X-linked genetic disease that predominantly affects males. It is caused by defects in the TAFAZZIN gene. The defect produces abnormal cardiolipin and dysfunctional mitochondria. It causes cardiomyopathy, low white-cell counts (neutropenia), muscle weakness, growth delay, fatigue and poor exercise tolerance. The FDA review estimates about 150 patients in the US and an incidence of 1 in 300,000–400,000 (FDA integrated review).
Forzinity is indicated “to improve muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kg.” The label sets the dose at 40 mg subcutaneously once daily (FDA label):
| Situation | Labeled dose |
|---|---|
| Weight at least 30 kg, eGFR ≥30 mL/min | 40 mg once daily |
| Adults with eGFR under 30 mL/min, not on dialysis | 20 mg once daily |
| Dialysis, or children with kidney impairment | No dosing recommendation (insufficient data) |
| Weight under 30 kg | Safety and effectiveness not established |
Continued approval may depend on a confirmatory trial. FDA agreed with the company on a global, randomized, double-blind, placebo-controlled trial in patients aged 5 years and older.
How the approval was reached
The approval was contested inside FDA, and the published review documents the disagreement (FDA integrated review):
- First cycle (May 2025). FDA issued a complete response letter. It could not conclude that elamipretide had an effect on any clinical endpoint, and it also cited manufacturing-facility deficiencies.
- Resubmission (August 2025). The company resubmitted, focusing on knee extensor strength as an “intermediate clinical endpoint.”
- Split review. The clinical and statistical reviewers and the cross-discipline team leader recommended another rejection. They cited the open-label, uncontrolled design, patient attrition and the effort-dependent nature of strength testing.
- Signatory decision. The signatory authority approved it anyway, accepting more uncertainty than usual because the disease is very rare, serious and had no approved treatment.
What the research shows
Barth syndrome (TAZPOWER)
TAZPOWER was a randomized, double-blind, placebo-controlled crossover trial in 12 males with Barth syndrome. Each received 12 weeks of elamipretide 40 mg daily and 12 weeks of placebo, separated by a 4-week washout, followed by an open-label extension (Reid Thompson et al., Genet Med 2021).
- Randomized phase: neither primary endpoint was met. The 6-minute walk distance (p = 0.97) and the fatigue score (p = 0.89) did not differ from placebo, and no secondary endpoint reached even nominal significance (FDA integrated review).
- Open-label extension: 10 patients continued on elamipretide. At week 36, the 6-minute walk distance had improved by 95.9 m. By week 168, the cumulative improvement was 96.1 m in the 8 patients remaining (Thompson et al., Genet Med 2024).
The approval was based on knee extensor strength measured by handheld dynamometry, one of the secondary endpoints. Baseline median strength was 124 newtons. The label reports these descriptive changes from that baseline (FDA label):
| Phase and visit | n | Median change (newtons) | Range |
|---|---|---|---|
| Randomized, week 12, placebo | 12 | −5 | −31 to 48 |
| Randomized, week 12, elamipretide | 12 | 4 | −41 to 86 |
| Open-label, week 12 | 10 | 34 | 7 to 95 |
| Open-label, week 24 | 9 | 68 | 3 to 90 |
| Open-label, week 48 | 8 | 41 | −2 to 144 |
| Open-label, week 168 | 8 | 63 | 38 to 78 |
No strength gain was seen during the blinded 12 weeks. The gains appeared only once every patient knew he was on the drug. These are descriptive numbers with no control group, which is why FDA’s own reviewers disagreed about what they show.
Primary mitochondrial myopathy
Primary mitochondrial myopathies are genetic disorders of mitochondrial energy production that cause muscle weakness and exercise intolerance. Three randomized trials tested elamipretide:
| Trial | Design | Dose | Main result |
|---|---|---|---|
| MMPOWER (Karaa et al., Neurology 2018) | Phase 1/2, n = 36, 5 days | IV, 0.01–0.25 mg/kg/h over 2 h; 5 days of treatment | Highest dose: +64.5 m vs +20.4 m placebo on 6-minute walk (p = 0.053) |
| MMPOWER-2 (Karaa et al., J Cachexia Sarcopenia Muscle 2020) | Crossover, n = 30, 4 weeks per period | 40 mg SC daily | +19.8 m on 6-minute walk (95% CI −2.8 to 42.5; p = 0.083); fatigue scores nominally better |
| MMPOWER-3 (Karaa et al., Neurology 2023) | Phase 3, n = 218, 24 weeks | 40 mg SC daily | No benefit: −3.2 m on 6-minute walk (95% CI −18.7 to 12.3; p = 0.69); fatigue unchanged (p = 0.37) |
The largest and longest trial, MMPOWER-3, was clearly negative on both primary endpoints. The authors described it as Class I evidence that elamipretide does not improve walking distance or fatigue at 24 weeks in this population.
Heart disease
Elamipretide was first developed for the heart, and three cardiology trials were negative or limited to short-term imaging changes:
- Heart attack (EMBRACE STEMI). A one-hour IV infusion during primary angioplasty for anterior heart attack did not reduce infarct size, measured by the CK-MB enzyme, or improve MRI, angiographic or clinical outcomes (Gibson et al., Eur Heart J 2016).
- Heart failure, single infusion. In 36 patients with reduced ejection fraction, the highest of three doses briefly reduced left-ventricular end-diastolic (−18 mL) and end-systolic (−14 mL) volume at the end of a 4-hour infusion; the drug was undetectable by 24 hours (Daubert et al., Circ Heart Fail 2017).
- Heart failure, 4 weeks (PROGRESS-HF). In 71 patients randomized to placebo, 4 mg or 40 mg daily, neither dose improved end-systolic volume or ejection fraction compared with placebo (Butler et al., J Card Fail 2020).
Dry age-related macular degeneration
ReCLAIM-2 randomized 176 people aged 55 or older with geographic atrophy (an advanced form of dry macular degeneration) to 40 mg daily or placebo for 48 weeks. It missed both primary endpoints, low-light visual acuity and growth of the atrophic area. Nominal differences favored elamipretide on a secondary imaging measure of photoreceptor loss (Ehlers et al., Ophthalmol Sci 2025). The company has moved this indication into phase 3 (Shirley, Drugs 2026).
Aging muscle, endurance and recovery
Interest in SS-31 for “endurance” and “recovery” comes mainly from animal studies. In aged female mice, 8 weeks of SS-31 at 3 mg/kg/day restored maximal mitochondrial ATP production in muscle and increased treadmill endurance (Campbell et al., Free Radic Biol Med 2019).
The only randomized human study in older adults was much narrower. In 39 healthy people aged 60–85 selected for poorly functioning muscle mitochondria, a single 2-hour IV infusion raised maximal ATP production in a small hand muscle immediately afterward. The effect was gone by day 7, and the infusion did not improve the muscle’s fatigue resistance (Roshanravan et al., PLoS One 2021).
About “endurance” and “recovery” claims. No controlled trial has tested elamipretide in healthy young adults or athletes, for exercise performance, muscle growth or injury recovery. In people with genetic mitochondrial muscle disease, the 218-patient phase 3 trial found no improvement in walking distance or fatigue. The positive endurance data are from aged mice.
Side effects and risks
Injection site reactions
Injection site reactions are the most common adverse effect. In the 12-patient placebo-controlled Barth trial (FDA label):
| Reaction | Elamipretide (n = 12) | Placebo (n = 12) |
|---|---|---|
| Any injection site reaction | 12 (100%) | 8 (67%) |
| Redness (erythema) | 12 (100%) | 3 (25%) |
| Pain | 9 (75%) | 5 (42%) |
| Hardening (induration) | 8 (67%) | 2 (17%) |
| Itching (pruritus) | 8 (67%) | 2 (17%) |
| Bruising | 3 (25%) | 0 |
| Hives (urticaria) | 3 (25%) | 0 |
The pattern was similar in other trials. In MMPOWER-2, 80% of patients on elamipretide had injection site reactions, mostly mild (Karaa et al., 2020). In ReCLAIM-2, adverse events occurred in 86% on elamipretide and 71% on placebo, led by injection site reactions (Ehlers et al., 2025).
Hypersensitivity
The label carries a warning for hypersensitivity, including serious allergic reactions that needed emergency treatment. Reactions included rash, papular lesions, eczema-like dermatitis and cough, and occurred anywhere from minutes to months after starting. A serious hypersensitivity reaction to elamipretide is the label’s only contraindication. In one case reviewed by FDA, a patient developed cough and a widespread rash 15 minutes after an injection on day 28 of treatment and was given adrenaline by paramedics (FDA integrated review).
Eosinophilia
Eosinophils (a type of white blood cell involved in allergy) often rose in studies lasting 30 days or longer. Counts peaked around day 90, with a mean rise of about 0.5–0.6 × 10³/µL, and returned to baseline after 6–12 months of continued use or after stopping. In the Barth trial, 9 of 12 treated patients had mild eosinophilia, without related symptoms.
Other label points
- Benzyl alcohol. The solution contains benzyl alcohol (20 mg/mL) as a preservative and is not for use in neonates, because of the risk of fatal “gasping syndrome.”
- Kidney impairment. Exposure rises with declining kidney function; the dose is halved below an eGFR of 30 mL/min.
- Overdose. No overdoses occurred in trials. The label expects histamine-related signs such as low blood pressure and near-fainting.
- Drug interactions. In vitro, elamipretide did not inhibit or induce the main CYP liver enzymes but did inhibit the kidney transporter MATE1. It did not change the effects of aspirin, clopidogrel or heparin in clinical studies. FDA required a further drug-interaction study after approval.
- Long-term unknowns. Carcinogenicity studies have not been done; FDA required two after approval. The Barth safety database is 12 patients, with about 26 person-years of open-label exposure. Trials in macular degeneration and mitochondrial myopathy added 132 person-years (FDA integrated review).
No trial has studied use outside these medical settings, at other doses, or in combination with other performance drugs.
Legal status and use outside medicine
In the US, elamipretide is a prescription drug, approved only for Barth syndrome in patients weighing at least 30 kg (Drugs@FDA). Product sold online as “SS-31” for research or self-use is not the FDA-approved product, and nothing guarantees its identity, purity, dose or sterility.
Elamipretide is not named on the WADA 2026 Prohibited List. The list’s S0 class covers pharmacological substances with no current approval by any government health authority for human therapeutic use. Elamipretide has held US approval since September 2025.
Key takeaways
- A mitochondrial peptide, not an anabolic. Elamipretide is a four-amino-acid peptide that binds cardiolipin in the inner mitochondrial membrane. It has no hormonal or growth-factor activity.
- One narrow approval. FDA granted accelerated approval in September 2025 to improve muscle strength in Barth syndrome, an ultra-rare disease with about 150 US patients, at 40 mg once daily.
- Thin and contested evidence. The approval rests on open-label strength gains in 10 patients after the blinded phase showed no benefit. FDA’s clinical reviewers recommended against approval.
- Negative large trials. The 218-patient phase 3 trial in mitochondrial myopathy, and trials in heart attack and heart failure, did not meet their main goals.
- Short half-life, daily injections. The half-life is about 3–4 hours, and the drug is cleared through the kidneys. Injection site reactions occurred in every treated Barth patient, and serious allergic reactions have occurred.
- No human evidence for performance use. Endurance and recovery claims rest on mouse studies; no trial has tested it in healthy adults or athletes.
Sources
- Stealth BioTherapeutics. Forzinity (elamipretide) injection, prescribing information, NDA 215244. FDA; DailyMed.
- Food and Drug Administration. Drugs@FDA: NDA 215244, Forzinity (elamipretide hydrochloride). Drugs@FDA.
- Food and Drug Administration, Center for Drug Evaluation and Research. Integrated review, NDA 215244 (Forzinity, elamipretide), 2025. FDA.
- National Center for Biotechnology Information. Elamipretide, PubChem CID 11764719. PubChem.
- Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279(33):34682–34690. PubMed.
- Szeto HH, Birk AV. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clin Pharmacol Ther. 2014;96(6):672–683. PubMed.
- Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250–1261. PubMed.
- Reid Thompson W, 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. Genet Med. 2021;23(3):471–478. PubMed.
- Thompson WR, Manuel R, Abbruscato A, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138. PubMed.
- 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. PubMed.
- Karaa A, Haas R, Goldstein A, et al. A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy. J Cachexia Sarcopenia Muscle. 2020;11(4):909–918. PubMed.
- 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. PubMed.
- Gibson CM, Giugliano RP, Kloner RA, et al. EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J. 2016;37(16):1296–1303. PubMed.
- Daubert MA, Yow E, Dunn G, et al. Novel mitochondria-targeting peptide in heart failure treatment: a randomized, placebo-controlled trial of elamipretide. Circ Heart Fail. 2017;10(12):e004389. PubMed.
- Butler J, Khan MS, Anker SD, et al. Effects of elamipretide on left ventricular function in patients with heart failure with reduced ejection fraction: the PROGRESS-HF phase 2 trial. J Card Fail. 2020;26(5):429–437. PubMed.
- 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. PubMed.
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- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.