SS-31

Origin and structure

SS-31 comes from the laboratory of the pharmacologist Hazel Szeto at Weill Cornell Medical College in New York, who worked on it with Peter Schiller; the letters SS stand for their two names. In a 2004 paper they described a family of small peptides built from alternating aromatic and basic (positively charged) amino acids that cross cell membranes and concentrate about 1,000-fold in the inner mitochondrial membrane. SS-31 became the lead compound. Its sequence is D-arginine, 2′,6′-dimethyltyrosine, lysine and phenylalanine amide (D-Arg-Dmt-Lys-Phe-NH2), its formula C32H49N9O5 (about 640 g/mol), and in the medicine it is present as the hydrochloride salt.

Stealth BioTherapeutics developed it under the code MTP-131 and, in early trials, the name Bendavia; elamipretide is its international non-proprietary name and Forzinity its US brand name. The early clinical programme gave intravenous infusions to try to limit damage to the heart and kidneys when blood flow returns after a blockage. Later trials moved to daily injections under the skin in inherited mitochondrial diseases and in eye disease.

How it is thought to work

Mitochondria make most of the cell's ATP, its energy carrier, on the folds of their inner membrane, the cristae. Cardiolipin is a lipid of that inner membrane, and the FDA label describes elamipretide as a 'mitochondrial cardiolipin binder' that settles in the inner membrane and improves the shape and function of mitochondria.

The first papers presented SS-31 as an antioxidant: the dimethyltyrosine was meant to neutralise reactive oxygen species, and in cells and isolated mitochondria the peptide reduced oxidative damage and mitochondrial swelling. Later work shifted the explanation towards its binding to cardiolipin, which is thought to stabilise the cristae and improve how efficiently oxygen use is turned into ATP. Almost all of this comes from cells, isolated mitochondria and animals.

In people, the first direct test of the idea was a randomised trial in 39 older adults whose muscle mitochondria worked poorly: a single 2-hour infusion raised the maximum rate of ATP production in a hand muscle straight afterwards, a borderline result statistically; the effect had gone a week later, and the muscle did not tire less. After an injection under the skin, blood levels peak within 0.5 to 1 hour, about 92% of the dose is absorbed, and practically all of it leaves in the urine within 48 hours, as unchanged peptide or two inactive breakdown products; in laboratory tests the liver did not break it down.

Is SS-31 approved?

In the US, yes, for one narrow use. In the EU, no.

Barth syndrome is a rare inherited disease in which the mitochondria lack normal cardiolipin; because it is X-linked, it almost only affects boys and men. Stealth submitted its application to the FDA in January 2024. On 15 May 2025 the FDA declined to approve it; after a resubmission in August 2025 it granted accelerated approval on 19 September 2025. Forzinity is indicated to improve muscle strength in adults and children with Barth syndrome who weigh at least 30 kg; below that weight safety and effectiveness have not been established. Accelerated approval means the FDA accepted an intermediate measure, here the strength of the muscles that straighten the knee, instead of proof of clinical benefit. The drug also holds a US orphan drug designation for this use, and the approval earned the company a rare paediatric disease priority review voucher.

Continued approval depends on a randomised, double-blind, placebo-controlled trial in patients aged 5 and over, and the FDA can withdraw the approval if that trial fails to confirm benefit. This trial, 4TAZPower, started in July 2026 with a planned 48 participants and 72 weeks of treatment, and is due to finish in 2029; the final report to the FDA is scheduled for March 2030.

No medicine containing elamipretide is authorised in the EU or in the Netherlands. The European Commission, on the EMA's advice, has designated it an orphan medicine for Barth syndrome (20 May 2021; since April 2024 the sponsor is a Dutch-registered company, Atnahs Pharma Netherlands B.V.) and for myopathic mitochondrial DNA depletion syndrome (16 May 2022). An orphan designation brings scientific support and, once a medicine is authorised, market exclusivity, but it is not an authorisation. One phase 3 trial, NuPower, included a site at Radboudumc in Nijmegen.

Research-grade SS-31 is not Forzinity. Forzinity is a ready-to-use solution made and tested under a US licence. Research peptide sold for laboratory use has no marketing authorisation anywhere and may not be used in people.

What the research shows

More than 20 trials of elamipretide are registered on ClinicalTrials.gov. The ones that matter most, controlled and uncontrolled kept apart:

• TAZPOWER, controlled phase (Barth syndrome): 12 men aged 12 to 35 received elamipretide and placebo for 12 weeks each, in random order with a 4-week break in between. Neither main endpoint, the six-minute walk test and a fatigue score, improved compared with placebo, and knee strength barely moved (median +4 newtons on elamipretide, −5 on placebo).
• TAZPOWER, open-label extension (uncontrolled): 10 men continued on elamipretide and 8 reached week 168. Compared with the start of the extension they walked a cumulative 96.1 metres further at week 168, and knee strength, from a median of 124 newtons at the start of the trial, was a median 63 newtons higher. There was no placebo group in this phase; it is the result behind the FDA approval.
• MMPOWER-3 (Neurology 2023), primary mitochondrial myopathy: 218 people aged 16 to 80, 24 weeks of daily injections or placebo. Walking distance did not differ (−3.2 metres, 95% CI −18.7 to 12.3), and neither did fatigue. In an exploratory analysis that the authors call post hoc, the 58 participants with defects in nuclear DNA walked about 25 metres further on elamipretide than on placebo. NuPower, a phase 3 trial in 102 people with such defects, ended in December 2024; no results have been posted on the registry.
• Heart: in EMBRACE STEMI (Eur Heart J 2016; about 300 people with a first anterior heart attack) an infusion started just before the procedure to reopen the artery and continued for an hour afterwards did not reduce infarct size. In PROGRESS-HF (J Card Fail 2020; 71 people with heart failure and reduced pumping function) four weeks of daily injections at two doses did not change the volume of the left ventricle compared with placebo.
• Dry age-related macular degeneration, ReCLAIM-2 (Ophthalmology Science 2025): 176 people with geographic atrophy, 48 weeks of treatment. Both main endpoints, vision in low light and growth of the atrophic area, were missed; the authors report slower loss of the photoreceptor layer as a nominal finding. The phase 3 trial ReNEW has enrolled 313 people for 96 weeks of treatment; its primary completion is expected in August 2027.
• Ageing: in a randomised trial in 39 healthy adults aged 60 to 85 with poorly working muscle mitochondria (PLoS One 2021), one infusion briefly raised the maximum ATP production of a hand muscle, a borderline result, but did not improve fatigue resistance. In old mice, a single dose or eight weeks of treatment improved muscle energy production and fatigue resistance. A small open-label 4-week safety study in people aged 65 to 80 (SHAPE, 30 planned) is listed as recruiting, though its registry entry has not been updated since December 2025. No controlled trial has measured lifespan, everyday energy or sports performance.

Side effects and warnings

Injection-site reactions are close to universal. In the Barth crossover trial, redness occurred in all 12 patients on elamipretide against 3 of 12 on placebo, pain in 9 against 5, hardening and itching in 8 each against 2, and bruising and hives in 3 against none. In ReCLAIM-2, 86% on elamipretide reported an adverse event against 71% on placebo, most often injection-site reactions; in MMPOWER-3 most adverse events were mild to moderate.

The US label warns of hypersensitivity, including serious allergic reactions that needed emergency treatment, with rash, eczema-like skin reactions or cough, from minutes to months after the start; anyone who has had a serious reaction should not receive it again. Eosinophils, a type of white blood cell, often rose in the first months (peaking around day 90) and returned to baseline within 6 to 12 months, without symptoms. An overdose is expected to cause histamine-like effects such as low blood pressure and near-fainting.

Forzinity contains the preservative benzyl alcohol and is not approved for newborns. The dose is halved in severe kidney impairment, because the peptide and its breakdown products leave through the kidneys. No carcinogenicity studies had been done by the time of approval; the FDA required a 26-week study in mice and a 2-year study in rats, the latter due in 2029, as well as a study of the interaction with metformin, because elamipretide blocks the drug transporter MATE1 in the laboratory. The safety data behind the approval cover 12 patients; the larger trials add exposure, but in other diseases. Research-grade SS-31 has no safety data of its own.

Frequently asked questions

Is SS-31 the same as elamipretide and Forzinity?

It is the same molecule: SS-31 is the original laboratory code, elamipretide the international non-proprietary name, and Forzinity the US medicine. Forzinity is a licensed, ready-to-use solution with a known strength, made and tested under pharmaceutical rules. Research-grade SS-31 is a peptide sold for laboratory use; its identity and purity are what a certificate of analysis says, nothing more, and it may not be used in people.

Is SS-31 legal in the Netherlands?

There is no registered medicine containing elamipretide in the Netherlands or anywhere else in the EU; Forzinity is a US product. The EMA's orphan designations for Barth syndrome and for mitochondrial DNA depletion syndrome support development but are not an authorisation. Research-grade SS-31 is sold for laboratory research, not as a medicine, and may not be used in people.

Why did the FDA approve it when the controlled trial missed its goals?

Under accelerated approval. In TAZPOWER's 12-week placebo-controlled phase neither walking distance nor fatigue improved. In the open-label extension knee strength rose, a median 63 newtons above the starting value by week 168 in 8 patients, and the FDA accepted that intermediate measure for this rare disease. It first declined the application in May 2025 and approved it in September 2025 after a resubmission, on condition that a placebo-controlled trial confirms benefit; if it does not, the approval can be withdrawn.

Does SS-31 slow ageing or give more energy?

That has not been shown in people. In old mice, single doses and longer treatment improved muscle energy production and fatigue resistance. In the one controlled human study, in 39 adults aged 60 to 85, a single infusion raised the maximum ATP production of a hand muscle for a short time, a borderline result, but did not make the muscle tire less, and the effect had gone after a week. A small open-label safety study in older adults is registered; no trial has measured lifespan, everyday energy or performance.

Is SS-31 banned in sport?

It is not named on the WADA Prohibited List for 2026 or 2027, which the Dopingautoriteit applies in the Netherlands. The list's catch-all class S0 covers substances with no approval by any government health authority for human therapeutic use; elamipretide has had FDA approval since September 2025, so it falls outside S0, and it is not named in any of the other classes, such as the metabolic modulators in S4.

Storage and handling

Store according to product-label instructions and batch handling notes. Lyophilized research peptides are commonly kept dry, protected from light, and handled with clean laboratory technique.

References

Checked against these sources on 28 October 2026.

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