SS-31 Guide: Evidence & Sourcing

SS-31 at a glance

What it is

A synthetic mitochondria-targeting tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2 (Dmt = 2',6'-dimethyltyrosine). C32H49N9O5, average molecular weight 639.8 Da, PubChem CID 11764719. Known across its development history as SS-31, MTP-131, Bendavia and elamipretide; the approved product is Forzinity.

Approval status

FDA-approved in 2025 (Forzinity, elamipretide hydrochloride injection, Stealth BioTherapeutics) to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg. This is an accelerated approval based on an intermediate endpoint, with continued approval contingent on confirmatory trials.

Mechanism, per the label

"A mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function." That is the FDA-approved mechanism statement verbatim, not a paraphrase.

Approved dose

40 mg subcutaneously once daily, at the same time each day, in patients weighing at least 30 kg; reduced in severe renal impairment. Research-community discussion typically reports far lower figures, with no study behind them.

What the trial found

The randomised crossover trial in 12 Barth syndrome patients did not beat placebo on either primary endpoint (6-minute walk distance and Total Fatigue Score). Approval rests on knee extensor muscle strength, a secondary endpoint, and gains appeared only during the open-label extension rather than the randomised period.

Pharmacokinetics

From the label: exposure is dose-proportional from 2 to 80 mg with minimal accumulation; Tmax 0.5-1 hour; absolute subcutaneous bioavailability approximately 92%; volume of distribution ~0.5 L/kg; plasma protein binding ~39%; roughly 100% of the dose recovered in urine within 48 hours.

Half-life

The label does not state one. It gives Tmax, bioavailability, distribution, metabolism and complete urinary recovery by 48 hours, but no elimination half-life figure - so numbers quoted elsewhere are not coming from the label.

Formulation contrast

The approved product is a ready-to-use 80 mg/mL aqueous solution preserved with benzyl alcohol, discarded 8 days after first puncture. Research-market SS-31 ships lyophilised and has to be reconstituted, which is why the arithmetic on this page exists.

Research-market status

SS-31 sold as a lyophilised research vial is not the approved product, is not approved for any use in that form, and is supplied for research and educational use only.

Educational reference. This page does not publish dose ranges or reconstitution arithmetic.

What it is / mechanism

SS-31 is a tetrapeptide with an unusual design brief: get into the inner mitochondrial membrane and stay there. Its sequence is D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine, and the alternating aromatic-cationic pattern is the point rather than an accident. The molecule carries a net positive charge that draws it toward the strongly negative membrane potential inside mitochondria, and the aromatic residues give it enough lipophilicity to partition into the membrane once it arrives. The D-arginine at the N-terminus is there for stability: swapping in the D-isomer makes the peptide substantially more resistant to the aminopeptidases that would otherwise chew it from that end. Molecular weight is 639.8 Da (C32H49N9O5), which is large for a tetrapeptide because of the dimethylated tyrosine. The FDA-approved label states the mechanism in one sentence: elamipretide is "a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane and improves mitochondrial morphology and function." It is worth pausing on how unusual it is to be able to quote a regulator-reviewed mechanism statement for a compound in this market. Almost every other peptide on a research-supplier site has a mechanism section assembled from primary papers and inference. This one has a mechanism section that a regulatory agency reviewed and permitted. Cardiolipin is what makes the target specific. It is a phospholipid found essentially only in the inner mitochondrial membrane, where it makes up a large fraction of the lipid content and does structural work that ordinary phospholipids do not. Cardiolipin stabilises the cristae - the folds that give the inner membrane its enormous surface area - and it physically organises the respiratory chain complexes, holding them in the supercomplex arrangements that make electron transport efficient. It also anchors cytochrome c to the membrane. When cardiolipin is damaged by oxidation or is abnormal in structure, cristae architecture degrades, respiratory supercomplexes disassemble, electron transport becomes leakier, and cytochrome c is released more readily. SS-31 binds cardiolipin and, on the model the development programme was built around, restores that architecture rather than adding an antioxidant or a substrate. Barth syndrome is why this mechanism found a clinical home. It is a rare X-linked disorder caused by mutations in the tafazzin gene, whose product remodels cardiolipin into its mature form. Patients therefore have structurally abnormal cardiolipin from birth, along with cardiomyopathy, skeletal muscle weakness and neutropenia. A drug whose entire mechanism is cardiolipin binding and cristae stabilisation is about as mechanistically targeted at that disease as a molecule can be, which is why the indication that ultimately succeeded was this one rather than the larger populations the programme originally pursued. The compound's name history is worth untangling, because it causes real confusion in supplier listings and search results. It originated in academic work as SS-31 - the Szeto-Schiller series, hence the SS - was developed clinically as MTP-131, carried the trade name Bendavia during its cardiovascular reperfusion-injury phase, was renamed elamipretide as its international non-proprietary name, and is marketed as Forzinity. Five names, one molecule. A research supplier listing "SS-31" and a pharmacy dispensing "Forzinity" are referring to the same peptide, though not to the same product - the formulations are entirely different, as the reconstitution section explains. One thing the mechanism does not do is generalise as easily as it reads. A molecule that improves mitochondrial membrane architecture sounds as though it should help any condition with mitochondrial involvement, and that is precisely the reasoning the clinical programme tested at scale across primary mitochondrial myopathy, cardiovascular reperfusion injury, heart failure and retinal disease. The results of those trials are covered in the evidence and dosage sections, and they are a useful lesson in how far a clean mechanism carries on its own.

Researched effects

The effect claims for SS-31 are best read in two columns: what the approved label supports, and what the wider trial programme actually produced. The label supports one thing, narrowly. Forzinity is indicated to improve muscle strength in adult and paediatric Barth syndrome patients weighing at least 30 kg, and the approval is an accelerated one based on knee extensor muscle strength measured by handheld dynamometry - explicitly described in the label as an intermediate clinical endpoint, with continued approval contingent on verification of clinical benefit in confirmatory trials. That is a real, regulator-reviewed efficacy finding in a rare disease, and it is the only approved effect claim that exists for this molecule anywhere. The registration trial itself is worth describing honestly, because it is more complicated than "approved for Barth syndrome" implies and no commercial page seems to say so. It enrolled 12 patients, aged 12 to 35, with genetically confirmed Barth syndrome, in a double-blind placebo-controlled crossover design: 12 weeks of elamipretide, a 4-week washout, 12 weeks of placebo, or the reverse order. The primary endpoints were distance walked in a 6-minute walk test and Total Fatigue Score on the Barth Syndrome Symptom Assessment. The label states plainly that Forzinity was not superior to placebo on those primary endpoints. Ten patients completed and entered an open-label extension; eight reached Week 168 and three reached Week 192. Knee extensor strength - a secondary endpoint - showed no increase during the randomised trial, and increases were observed during the extension period. Median baseline strength was 124 newtons (range 92 to 176). So the approved effect rests on a secondary endpoint that moved in an uncontrolled open-label extension rather than in the randomised comparison, in a total population of twelve people. That is not a reason to dismiss it - in an ultra-rare disease with no alternative, regulators weigh evidence differently, and the accelerated-approval pathway exists precisely for this situation, with the confirmatory-trial requirement as the safeguard. It is a reason to be accurate about what has and has not been demonstrated, especially when the same molecule is sold as a research chemical to people extrapolating from the word "approved." Outside Barth syndrome, the record is largely one of well-designed trials that did not deliver. The clinical programme was broad and serious: a Phase 3 trial in primary mitochondrial myopathy, terminated; earlier intravenous work on reperfusion injury in patients undergoing angioplasty under the Bendavia name, terminated; multiple Phase 1/2 studies in mitochondrial myopathy and skeletal muscle function; and topical ophthalmic formulations tested in Phase 2. A Phase 3 study of subcutaneous elamipretide in retinal disease remains active. The pattern across that programme is the substantive finding: a compound with a clean, specific, well-characterised mechanism repeatedly failed to convert it into endpoint-level benefit in larger populations, and succeeded only in the rare disease where the mechanism maps onto the causal defect directly. What gets reported in research-community settings - improved endurance, faster recovery, subjective energy - has no controlled data behind it at all. It is not supported by the label, which makes no such claim, and it is not supported by the failed trials, several of which were specifically powered to detect exactly that kind of functional improvement in people with genuine mitochondrial impairment. Anyone reading anecdotal reports of an energy effect should weigh them against a 6-minute walk test that did not separate from placebo. Nothing here is a claim that SS-31 treats, prevents or improves any condition outside its single approved indication, and nothing here is medical advice.

Research timeline

Dated milestones taken from the primary records: the molecule's discovery, its first registered human study, the trials that shaped the evidence and the regulatory decisions. Each entry links to the record it comes from.

1. Aug 13, 2004The Szeto–Schiller laboratory at Weill Cornell describes its cell-permeable peptide antioxidants: they concentrate about 1,000-fold in the inner mitochondrial membrane, protect cells and isolated mitochondria from oxidative damage and improve contraction in an isolated-heart model; analogues without dimethyltyrosine do not. PMID 15178689
2. Apr 2016EMBRACE STEMI, the phase 2a heart-attack trial of intravenous MTP-131 given during coronary stenting, is published: it was safe and well tolerated but did not reduce infarct size, which ended the cardiac reperfusion programme's main hypothesis. PMID 26586786
3. Apr 2018MMPOWER, a phase 1/2 trial in 36 adults with primary mitochondrial myopathy, reports a dose-dependent increase in six-minute walk distance after five days of intravenous elamipretide; other efficacy and safety measures did not differ from placebo. PMID 29500292
4. Aug 2020MMPOWER-2, a four-week crossover trial of daily subcutaneous elamipretide in the same condition, misses its primary endpoint (19.8 m more on the six-minute walk, not significant) while fatigue questionnaires improve; injection-site reactions affected 80% of participants. PMID 32096613
5. Mar 2021TAZPOWER, the Barth syndrome trial, is published: in its randomised crossover part (12 patients) neither primary endpoint was met; in the open-label extension walk distance, symptom scores and knee-extensor strength improved after 36 weeks, without a placebo comparison. PMID 33077895
6. Jul 2023MMPOWER-3, the phase 3 trial in 218 adults with primary mitochondrial myopathy, did not meet either primary endpoint after 24 weeks: walk distance and fatigue scores were no better than with placebo; the drug was well tolerated. PMID 37268435
7. Apr 2024A 52-week trial of elamipretide eye drops in 12 patients with Leber hereditary optic neuropathy misses its primary endpoint: visual acuity did not improve against vehicle-treated eyes. PMID 37923251
8. Sep 19, 2025FDA grants accelerated approval to Forzinity (elamipretide, Stealth BioTherapeutics) as a new molecular entity, to improve muscle strength in Barth syndrome patients weighing at least 30 kg; continued approval depends on confirmatory trials. FDA · NDA 215244

Records checked Oct 3, 2026

Claims at a glance

The claims most often made about this compound, each with the strongest kind of evidence we found for it. The grade says what was studied, not whether the claim is true; the line beside it says what that study showed.

• Increases walking distance and exercise capacityHuman, randomised trial. The largest trial, 218 people with mitochondrial myopathy over 24 weeks, was stopped after its double-blind part missed its primary endpoints; placebo walked slightly farther. NCT03323749
• Reduces fatigueHuman, randomised trial. Two double-blind trials made fatigue a primary endpoint, in Barth syndrome and in mitochondrial myopathy; neither found a difference from placebo. PMID 33077895
• An approved treatment for Barth syndromeHuman, randomised trial. FDA granted accelerated approval in September 2025 on knee strength; in the 12-person randomised period placebo gained more, and the gains came in the open-label extension. NCT03098797
• Improves heart function in heart failureHuman, randomised trial. In a 28-day randomised trial of 71 people with stable heart failure, neither heart volume nor ejection fraction improved more than on placebo. NCT02788747
• Protects the kidneysHuman, randomised trial. A 16-person pilot around kidney-artery stenting was stopped early; on its registered main measure the drug group gained less than placebo, while the paper reports gains on other measures. NCT01755858
• Slows vision loss in macular degenerationHuman, randomised trial. A 48-week double-masked trial of 176 people did not meet its primary endpoints; a phase 3 on photoreceptor loss, a different endpoint, reports from 2027. NCT03891875
• Rejuvenates ageing skinNo study found. A PubMed search pairing SS-31 or elamipretide with skin, ageing, wrinkle and collagen terms found no human skin study (17 records, Oct 2026), only delivery-vehicle work on tissue. PubMed search, Oct 6, 2026

The reasoning behind each grade, study by study, is in this guide's Benefit & Outcome Review.

Grades checked Oct 6, 2026

Half-life & pharmacokinetics

The FDA-approved label does not state an elimination half-life for elamipretide. That is worth saying explicitly, because it is a genuinely unusual gap in an otherwise detailed pharmacokinetics section, and because half-life figures for SS-31 do circulate without attribution. What the label does provide is substantial, and in practice more useful than a single number. Exposure increases proportionally across a dose range of 2 to 80 mg with daily subcutaneous injection, and accumulation is minimal - which is itself the most practically relevant half-life statement available, since a compound that does not accumulate on once-daily dosing is clearing substantially within the dosing interval. Maximum concentrations are reached 0.5 to 1 hour after subcutaneous administration, so absorption is fast. Absolute subcutaneous bioavailability is approximately 92%, which is high, and exposure is comparable between thigh and abdominal injection. Distribution is throughout total body water at a volume of approximately 0.5 L/kg, with low plasma protein binding of around 39%. Elimination is characterised in structural terms rather than temporal ones. Elamipretide is metabolised by sequential C-terminal degradation to an M1 tripeptide and an M2 dipeptide, neither of which has pharmacological activity, and parent plus both metabolites are excreted in urine, with approximately 100% of the dose recovered there by 48 hours in patients with normal renal function. Complete urinary recovery within 48 hours puts a real outer bound on how long the molecule and its fragments persist, even without a stated t-half. The practical reading is that this behaves as a rapidly absorbed, rapidly and renally cleared peptide dosed once daily without accumulation, and that once-daily dosing in the approved regimen reflects that profile rather than a long duration of action. If you encounter a specific half-life figure for SS-31, it did not come from the approved label - which is the most authoritative pharmacokinetic source that exists for this compound - and the useful question is which study did produce it.

Storage & handling

• The approved product's storage tells you what the molecule tolerates: Forzinity is stored refrigerated at 2-8 C and must not be frozen. After the first dose, the opened vial may be kept refrigerated or at room temperature between 20-25 C.
• Discard 8 days after first opening. This in-use limit is set by the benzyl alcohol preservative rather than by peptide stability, and it is a useful calibration point for anyone judging how long a reconstituted multi-dose vial should be trusted.
• Research-market SS-31 lyophilised and unopened: store cold and dark, typically at -20 C for long-term storage, with refrigeration generally described as adequate for shorter periods. Keep the vial in its carton.
• After reconstitution with bacteriostatic water: refrigerate at roughly 2-8 C and do not freeze. Freeze-thaw cycling degrades peptides in solution and is the most common avoidable handling error.
• Add bacteriostatic water slowly down the inside wall of the vial rather than onto the powder, swirl rather than shake, keep the stopper clean and use a fresh needle for each withdrawal. Mechanical agitation causes aggregation, and no preservative compensates for repeated entry with a contaminated needle.

Evidence File

The SS-31 Evidence File: 29 Trials and Four Traced Numbers

Elamipretide has been registered on ClinicalTrials.gov under five different names, and the registry does not cross-index them, so a search on the international non-proprietary name alone returns an incomplete programme. It also has something almost no research-market peptide has: a registry results database entry for fourteen of its trials, in which the sponsor posted the actual arm-by-arm numbers, including for the trials that failed. Those posted tables are a separate document from any journal publication and are rarely quoted anywhere. This module works from them, trial by trial, and traces the figures that circulate about this compound back to the documents they came from.

• 29 interventional trials of this molecule enumerated
• 9 studies an INN-only registry search does not return
• 4 circulating claims traced, one of them to no source at all
• 456 subjects of completed but unreported trial data

Sourcing File

The SS-31 Sourcing File: Salt Form, Stereochemistry and the Certificate Gap

Elamipretide is registered with the FDA's substance registry twice - once as a free base and once as a salt, each with its own registry identifier, its own CAS number and its own molecular weight. The approved brand name is attached to the salt. That distinction is invisible on a research-vial label and invisible to a purity figure, and it changes what a stated milligram amount means before any question of quality is asked. This module works through the identity numbers as registered, the arithmetic that follows from them, the impurities and look-alikes that are specific to this sequence, and which of them a standard certificate can and cannot exclude.

• 2 substances registered with the FDA under this molecule's name
• 1.53-fold spread in actual peptide from one 50 mg label
• 4 mass offsets separating SS-31 from its analogs and its likeliest degradant
• 2 chiral tests that would settle the D-arginine, neither standard on a certificate

Benefit & Outcome Review

The SS-31 Benefit and Outcome Review: 14 Claims Against the Human Record

Most peptides in this market are judged against rodent studies because nothing else exists. SS-31 is the unusual case where that is not necessary: elamipretide has been tested in randomised, placebo-controlled human trials in mitochondrial myopathy, Barth syndrome, heart failure, reperfusion injury, renal artery stenosis and macular degeneration, and most of those trials posted their numbers. This review takes the claims made for the compound one at a time, separates human data from animal data, states the effect size against the actual comparator rather than against baseline, and says plainly which claims have no human study behind them at all.

• 14 marketed claims judged against the human record
• 4 randomised trials measured six-minute walk distance
• 6 claims with no human study located
• 1 claim accepted by a regulator, on an intermediate endpoint

Guide FAQ

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