SS-31 (Elamipretide): Approved for One Disease, Failed in the Others

By Evan Marsh, EditorUpdated July 30, 2026Sources: FDA label, Phase 3 trial reports

Almost everything written about SS-31 is out of date, and in the same direction: it is described as a promising research peptide. It is not. It is an approved prescription drug — and separately, it failed the Phase 3 trial for the condition most buyers are actually hoping to treat. Both halves of that matter, and they are usually reported apart.

The short version. In September 2025 the FDA granted accelerated approval to elamipretide, sold as FORZINITY, to improve muscle strength in Barth syndrome — a genetic disease affecting roughly 150 people in the United States. In primary mitochondrial myopathy, the broader condition, its Phase 3 trial missed both co-primary endpoints. In heart failure, its trials were negative too.

What SS-31 actually is

SS-31 is a four-amino-acid peptide — D-Arg-2,6-dimethylTyr-Lys-Phe-NH₂ — that has collected an unusual number of names along the way: SS-31 in the academic literature, MTP-131 and Bendavia in earlier development, elamipretide as the international nonproprietary name, FORZINITY on the pharmacy label. They are one molecule.

Its defining property is where it goes. The peptide concentrates roughly a thousandfold in the inner mitochondrial membrane, and once there it binds cardiolipin — the phospholipid that holds the cristae folds in shape and organises the electron transport chain along them. When cardiolipin is disrupted, the cristae flatten and electron transport becomes leaky and inefficient.

That is why the mechanism is structural rather than antioxidant. Early work described the SS peptides as targeted antioxidants; the later and better-supported account is that SS-31 restores membrane architecture, and the improvement in oxidative stress follows from that rather than causing it.

Barth syndrome: the approved indication

Barth syndrome is caused by mutations in TAZ, the gene for the enzyme that remodels cardiolipin. So the disease is, mechanistically, a cardiolipin problem — which makes it the most logical possible target for a cardiolipin-binding drug. That coherence is the strongest part of the SS-31 story.

The trial history is messier than the approval suggests. TAZPOWER enrolled just12 patients in a randomised crossover of 40 mg daily against placebo, 12 weeks per arm. Neither primary endpoint was met. Ten patients then continued into an open-label extension, eight completed 36 weeks, and there the results were substantial: a 95.9 metre improvement in six-minute walk distance and a 2.1-point improvement in symptom score, both statistically significant, alongside knee strength and cardiac measures.

The approval is accelerated, granted on knee extensor muscle strength as an intermediate endpoint, with continued approval contingent on a confirmatory trial. That trial is only now recruiting. In plain terms: a randomised phase that missed, an open-label extension that impressed, and a regulator willing to accept that for a disease with 150 patients and no other option.

Detail	Value
Approved product	FORZINITY (elamipretide HCl), NDA 215244
Approval date	19 September 2025, accelerated
Indication	Improve muscle strength in adult and pediatric Barth syndrome patients ≥ 30 kg
Dose	40 mg subcutaneously once daily
Volume	0.5 ml containing 40 mg elamipretide (46.8 mg as the HCl salt)
Sites	Abdomen or outer thigh, rotated
Most common adverse reactions	Injection-site reactions — erythema, pain, induration, pruritus, bruising, urticaria

Mitochondrial myopathy: where it failed

This is the part that gets left out. Primary mitochondrial myopathy is the condition SS-31 was developed for at scale, and the one that maps onto what people buying it want — fatigue, exercise intolerance, mitochondrial function. The Phase 3 trial tested exactly that, in 218 adults, and it did not work.

Co-primary endpoint	Difference at 24 weeks	95% CI	p
Six-minute walk distance	−3.2 metres	−18.7 to 12.3	0.69
Fatigue score (PMMSA)	−0.07	−0.10 to 0.26	0.37

Both endpoints missed, and the walk distance actually favoured placebo by a trivial margin. The trial was terminated after the readout.

A post hoc analysis later found a significant walk-distance improvement confined to patients whose disease came from nuclear-DNA rather than mitochondrial-DNA mutations. That is a genuinely interesting signal and it is also, by construction, hypothesis-generating: the subgroup was identified after the fact. A follow-up trial in exactly that population completed in December 2024 and its results have not been published — which is the single most useful thing to watch for anyone tracking this compound.

Heart failure: also negative

SS-31 was taken into cardiology under the name Bendavia, on the logic that failing heart muscle is energetically starved. The trials did not support it. The PROGRESS-HF Phase 2 trial in reduced-ejection-fraction heart failure and an earlier randomised trial both failed to demonstrate benefit on their primary endpoints, and no heart failure indication was pursued to approval.

A Phase 3 trial in dry age-related macular degeneration is running, with completion expected in 2027. So the development story is not over — it has simply gone narrow rather than broad.

Reconstitution, for the research-grade form

The approved product ships as a solution at a fixed concentration. Research-grade SS-31 is sold as lyophilised powder, so the volume has to be calculated. Note that the approved daily dose is 40 mg — a milligram-scale dose, unlike most peptides on this site, which means vials empty fast and the arithmetic is worth doing before ordering.

Vial	Water	Concentration	10 mg	20 mg	Doses at 40 mg
10 mg	2 ml	5 mg/ml	—	—	0.25
50 mg	2.5 ml	20 mg/ml	50 units	100 units	1.25
100 mg	5 ml	20 mg/ml	50 units	100 units	2.5

A 10 mg vial does not contain a single approved-strength dose. That is worth stating plainly, because vial sizes marketed for this compound frequently imply otherwise.

Peptide preset

Peptide in vial (mg)

Bacteriostatic water added (ml)

Desired dose (mcg)

—

Concentration (mcg / ml)

—

Volume to draw (ml)

—

Units on U-100 insulin syringe

—

Doses per vial

Draw to this mark on a 1 ml U-100 insulin syringe

Formula: concentration = peptide (mcg) ÷ water (ml). Volume = dose ÷ concentration. One unit on a U-100 insulin syringe = 0.01 ml. Values are for laboratory reference only.

How to read all this

SS-31 occupies an unusual position, and it deserves a more careful description than either side of the argument gives it. The mechanism is real and well characterised in strong journals. The approval is real. And the evidence in the condition people actually buy it for — general mitochondrial fatigue and exercise capacity — is a failed Phase 3 trial.

An approval for a 150-patient genetic disease is not an endorsement of mitochondrial supplementation. It is the opposite of a broad claim: the regulator accepted an intermediate endpoint in a population with no alternatives, and required a confirmatory trial to keep it. Anyone citing "FDA approved" for SS-31 without naming Barth syndrome is using a true fact misleadingly.

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Frequently asked questions

Is SS-31 approved by the FDA?

Yes — but for one ultra-rare disease, not for general mitochondrial health. In September 2025 the FDA granted accelerated approval to elamipretide as FORZINITY, to improve muscle strength in adults and children with Barth syndrome weighing at least 30 kg. Barth syndrome affects roughly 150 people in the United States.

Did SS-31 work for mitochondrial myopathy?

No. The Phase 3 MMPOWER-3 trial in 218 adults with primary mitochondrial myopathy missed both co-primary endpoints: the six-minute walk distance differed by −3.2 metres (p = 0.69) and the fatigue score by −0.07 (p = 0.37). That is the indication most people buying SS-31 have in mind, and it is the one where it failed.

What is the SS-31 dose?

The approved product is 40 mg subcutaneously once daily, injected into the abdomen or outer thigh with sites rotated. That figure comes from the Barth syndrome program, where a 12-week randomised phase also missed its primary endpoints and the open-label extension produced the gains that supported approval.

How does SS-31 work?

It concentrates roughly a thousandfold in the inner mitochondrial membrane and binds cardiolipin, a phospholipid that holds the cristae folds in shape and organises the electron transport chain. Restoring that architecture is the documented mechanism — it is a structural intervention, not an antioxidant in the usual sense.

Is SS-31 banned in sport?

It is not named in the 2026 WADA Prohibited List. Before its approval it would have been captured by the S0 catch-all for substances with no regulatory approval anywhere; now that a marketing authorisation exists, that clause no longer applies on its face. Anyone subject to testing should confirm with their anti-doping authority rather than rely on that reading.

Sources

Zhao K et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. Journal of Biological Chemistry, 2004;279(33):34682–90. PubMed
Birk AV 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):1250–61. PubMed
Karaa A 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
Karaa A et al. Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial. Orphanet Journal of Rare Diseases, 2024;19(1):431. PubMed
Reid Thompson W et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genetics in Medicine, 2021;23(3):471–478. PubMed
Butler J et al. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. Journal of Cardiac Failure, 2020;26(5):429–437. PubMed
Daubert MA et al. Novel Mitochondria-Targeting Peptide in Heart Failure Treatment: A Randomized, Placebo-Controlled Trial of Elamipretide. Circulation: Heart Failure, 2017;10(12). PubMed
Karaa A et al. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology, 2018;90(14):e1212–e1221. PubMed
FORZINITY (elamipretide) prescribing information, NDA 215244. DailyMed label
Trial registry: TAZPOWER, Barth syndrome (NCT03098797) and MMPOWER-3 (NCT03323749).

Related guides

Research use only. Research-grade SS-31 is not the approved prescription product. This page summarizes published trial data and the FDA label for informational purposes and is not medical advice.