What it is
SS-31 is the laboratory name for a synthetic aromatic-cationic tetrapeptide, D-arginine-2,6-dimethyltyrosine-lysine-phenylalanine amide, developed by Hazel Szeto and Peter Schiller and numbered the 31st compound in their peptide series. The molecule later carried the development codes MTP-131 and Bendavia, and its International Nonproprietary Name is elamipretide. As of 19 September 2025, elamipretide hydrochloride is also the active ingredient of an approved US drug, sold under the brand name FORZINITY. In the primary literature, SS-31, MTP-131, Bendavia and elamipretide all refer to the same chemical entity across every stage of its development; what changed over time was the salt form used in the marketed product and, most recently, its regulatory status.
That last point makes this entry different from most others on this site. Elamipretide is not simply an unapproved research peptide, and it is not simply an approved drug either. It is both, depending on who is selling it and for what.
Mechanism
SS-31 is described in the primary literature as an amphipathic, polybasic peptide that partitions into lipid bilayer interfacial regions and is proposed to concentrate at the inner mitochondrial membrane because that membrane is unusually rich in the anionic phospholipid cardiolipin. Biophysical and computational work in model bilayers, isolated mitochondria and a yeast system found that the peptide did not destabilize lamellar membranes even at high binding concentrations, but did alter lipid packing and membrane surface electrostatics, a mechanism the study’s authors proposed as the likely basis of its reported mitochondrial-protective effects, rather than a classical receptor interaction.
The clinical literature has repeated a downstream hypothesis built on that biophysical finding: that stabilizing cardiolipin preserves the organization of electron transport chain complexes, improves oxidative phosphorylation, and reduces reactive oxygen species leakage. That causal chain has not been measured directly in the same human trial in the sources reviewed for this entry. The trials that exist measured functional outcomes, such as walk distance and muscle strength, not electron transport chain efficiency in patients. A 2025 review on mitochondrial approaches to kidney injury identified a protein called phospholipid scramblase 3 as an emerging mediator of the peptide’s protective effects in preclinical models, while cautioning that mitochondrial peptide therapies including this one face translational hurdles including limited bioavailability, difficulty establishing effective dosing, and incomplete mechanistic understanding. That caveat, from researchers studying the compound’s own proposed mechanism, is worth holding onto when reading any of the sections below.
What is approved, and at what dose
A record of what the FDA had approved as of 18 September 2026, not an instruction.
FORZINITY (elamipretide hydrochloride injection) was granted accelerated approval on 19 September 2025 under New Drug Application 215244. The label states the indication as improving muscle strength in adult and pediatric patients with Barth syndrome weighing at least 30 kilograms. Barth syndrome is a rare, X-linked genetic disorder caused by mutations in the TAZ gene that impair remodeling of cardiolipin, the same lipid the peptide is proposed to bind.
The label’s own limitations-of-use language is the single sentence that governs how this entry should be read: the indication was approved under accelerated approval, based on an improvement in knee extensor muscle strength, described as an intermediate clinical endpoint, and continued approval may be contingent on verification of clinical benefit in a confirmatory trial. In plain terms, the drug was approved because it moved a muscle-strength surrogate in a small trial population, not because a completed trial demonstrated improved survival, cardiac function, or another outcome patients would directly feel. That confirmatory trial, registered as a Phase 3b/4 study in genetically confirmed Barth syndrome patients, was reported as recruiting as of this writing, with a primary completion date years away.
The approved dose is 40 mg injected subcutaneously once daily, reduced to 20 mg once daily in patients with severe renal impairment not on dialysis, rotated between the abdomen and outer thigh. There is no boxed warning. The label’s contraindication is limited to serious hypersensitivity to elamipretide or its excipients. Because the multi-dose vial is preserved with benzyl alcohol, the label states the product should not be used in neonates, a restriction that, combined with the 30-kilogram weight floor, excludes an approved use in the youngest and often most severely affected Barth syndrome patients. In the small trial that underlies the label, injection site reactions were reported in essentially all treated patients, and this pattern of frequent local reactions, not systemic toxicity, has been the dominant safety finding across the entire elamipretide program.
How the approval actually happened
The regulatory history behind that one approved sentence is unusually long and worth telling as a sequence rather than compressing into “approved.” Stealth BioTherapeutics submitted its first New Drug Application for elamipretide in Barth syndrome on 24 August 2021. The FDA issued a Refusal to File on 20 October 2021, a pre-review administrative rejection meaning the agency judged the application incomplete before review even began. Advocacy records show the application was subsequently reassigned between three different FDA review divisions over roughly two and a half years, reflecting difficulty classifying a therapy for a rare, multi-system disease within the agency’s organizational structure.
A resubmitted application was accepted for filing on 3 April 2024 and granted Priority Review the following month. On 10 October 2024, FDA’s Cardiovascular and Renal Drugs Advisory Committee voted 10 to 6 in favor of approval for the Barth syndrome indication. Despite that favorable vote, FDA issued a Complete Response Letter on 29 May 2025, declining to approve the application as submitted. Stealth announced a third resubmission on 18 August 2025, and FDA granted accelerated approval one month later, on 19 September 2025. The application was not killed by the Complete Response Letter; it was redirected, from a standard-approval submission toward one resting on the muscle-strength surrogate, and the redirected version succeeded.
The approval carries post-marketing requirements beyond the confirmatory efficacy trial, including a mouse carcinogenicity study and a two-year rat carcinogenicity study, meaning the drug reached the market before its long-term carcinogenic potential in standard rodent testing had been characterized.
Barth syndrome: the trial the approval rests on
The pivotal trial, known as TAZPOWER, was a small, randomized, double-blind, placebo-controlled crossover study at a single site, enrolling 12 male patients age 12 and older with genetically confirmed Barth syndrome, followed by a long open-label extension. In the open-label extension, reported at week 168, ten patients entered and eight completed. Six-minute walk distance improved at every assessed time point, reaching a cumulative improvement of 96.1 meters by week 168. Echocardiographic measures of left ventricular volume also improved over the same period, and a disease-specific lipid biomarker improved in a pattern the study’s authors reported as correlating with the clinical changes.
Because Barth syndrome is ultra-rare, a large placebo-controlled trial was not considered practical, so the sponsor built a retrospective natural-history comparison cohort of 19 untreated patients and compared it, via propensity scoring, to the eight patients who remained on treatment through the open-label extension. That comparison favored elamipretide on walk distance and handheld dynamometry-measured muscle strength. This is the strongest efficacy claim in the Barth syndrome program, and it should be read as exactly what it is: an uncontrolled, retrospective, propensity-matched comparison in a disease population of a few dozen genetically confirmed patients worldwide, not a randomized result.
Every other indication tested: a program of negative trials
Outside Barth syndrome, elamipretide has been tested across primary mitochondrial myopathy, dry age-related macular degeneration, heart failure, and acute heart attack, and every one of those programs failed on its stated primary endpoint.
In primary mitochondrial myopathy, the Phase 2 crossover trial MMPOWER-2 missed its primary six-minute-walk endpoint, reporting a 19.8-meter difference against placebo that did not reach significance, though several patient-reported fatigue measures improved. The Phase 3 trial that followed, MMPOWER-3, enrolled 218 patients and was terminated after not demonstrating a significant benefit in its overall, genotypically diverse population, according to the investigators’ own published account. A post hoc subgroup analysis suggested a possible effect in patients with mitochondrial DNA replisome-related disorders, but that subgroup finding came from a negative trial, and the dedicated follow-up study designed to test it, NuPOWER, completed without a located published result. There is no approved indication for elamipretide in primary mitochondrial myopathy of any genotype.
In dry age-related macular degeneration, the Phase 2 trial ReCLAIM-2 did not meet either of its co-primary endpoints, low-luminance visual acuity and geographic atrophy area. A secondary, exploratory endpoint measuring preservation of photoreceptor structure did show a statistically significant effect, and that surrogate has since been made the primary endpoint of an ongoing Phase 3 trial, ReNEW, which has not yet reported results. As of this writing there is no FDA approval and no completed Phase 3 result in this indication.
In heart failure, the Phase 2 trial PROGRESS-HF found no significant difference from placebo on its primary cardiac MRI endpoint in patients with reduced ejection fraction, with the trial’s own authors concluding the drug did not improve that measure. A larger acute decompensated heart failure trial enrolling more than 300 patients completed without a located published efficacy result. In first-time anterior heart attack undergoing emergency angioplasty, the Phase 2 trial EMBRACE STEMI found no difference in infarct size between elamipretide and placebo, and the authors reported no improvement on any prespecified imaging, electrocardiographic, or clinical outcome. There is no cardiovascular indication anywhere in this compound’s regulatory history.
Put together, the Barth syndrome approval is a narrow exception inside a much larger record of trials that did not confirm a clinical benefit. The evidence tier assigned to this entry, E1, reflects the genuine approved-label evidence that exists for Barth syndrome specifically. It does not extend to any other proposed use, all of which sit at a lower tier: failed or unproven Phase 2 and Phase 3 results, hypothesis-generating post hoc subgroups, or preclinical mechanism alone.
Safety
Injection site reactions are, by a wide margin, the most consistently reported adverse finding across the entire program, present from early Phase 1 studies through the approved label. In the trial underlying approval, erythema was reported in all treated patients against a quarter of placebo patients, with pain, pruritus and induration also more common on treatment. The Phase 2 dose-ranging trial in mitochondrial myopathy reported injection site reactions in 80 percent of treated participants, and the AMD trial ReCLAIM-2 reported adverse events in 86 percent of treated patients versus 71 percent on placebo, again dominated by local reactions.
No serious systemic safety signal has emerged across the trials reviewed, and multiple studies describe the drug as well tolerated at the systemic level, with the important caveat that most trials enrolled small numbers of patients and none has run long enough to characterize rare serious events. The longest published human exposure data are the Barth syndrome open-label extension at 168 weeks in a handful of patients and the AMD trial at 48 weeks. As noted above, the FDA’s own post-marketing requirements include carcinogenicity studies that had not completed at the time of approval.
What circulates
This compound is not on this site’s circulating-figures exclusion list, so what follows records the general pattern found in circulating research-peptide material, without naming any vendor, without a date, and without treating the figure as guidance.
Material sold as “SS-31” circulates as lyophilized powder in small vials, typically marketed under research-use-only framing. The route described in circulating material, subcutaneous, and the once-daily frequency both broadly match the studied and approved route and frequency, which is unusual for a compound on this site. Where circulating material states a dose, it commonly describes a daily amount of a few milligrams, which sits below the 40 mg once-daily dose used in essentially every late-stage human trial of this compound and in the approved FORZINITY label, including the Barth syndrome pivotal trial, both mitochondrial myopathy Phase 2 and 3 trials, the AMD Phase 2 trial, and one arm of the heart failure trial. Across every one of those late-stage trials, the studied subcutaneous dose is the same 40 mg once daily, which gives this comparison an unusually clean anchor: the approved and studied dose is consistent, and circulating material describing a lower daily figure sits below all of it, not above it, which is the less common pattern on this site.
Circulating material of this kind typically does not cite the FDA label’s approved dose, the accelerated-approval and surrogate-endpoint limitation, the benzyl-alcohol and neonatal warning, or the narrow Barth-syndrome-only indication, and it typically continues to describe the compound as a purely investigational research peptide, predating or ignoring the September 2025 approval. Where such material claims a general anti-aging, mitochondrial-support, or performance benefit, that claim conflicts directly with the single narrow indication on the approved label and with the negative results recorded above for heart failure, heart attack, and general-population mitochondrial myopathy.
Approved and warned against, at the same time
FDA issued a warning letter dated 24 August 2026 to a research-peptide vendor, naming “SS-31 (Elamipretide)” among several other compounds marketed on the vendor’s site, roughly eleven months after FORZINITY’s approval. The letter’s cited legal basis was that the vendor’s product is a new drug, lacking an approved application for the use for which it was being marketed, introduced into interstate commerce unlawfully. A second warning letter from the same period named the same compound alongside several others, indicating this was part of a coordinated sweep across multiple peptide products rather than an action aimed at elamipretide specifically.
The two facts sit side by side and both are true. Elamipretide hydrochloride is an FDA-approved prescription drug, sold as FORZINITY, for one narrow rare-disease indication, in patients weighing at least 30 kilograms, at a specific dose, under an approval that remains contingent on a confirmatory trial still years from reporting. The same molecule, sold by research-peptide vendors as “SS-31” for unsupervised use and for indications that were never demonstrated to work, or that failed outright in controlled trials, is not a lawful version of that drug and was the subject of a federal warning letter after the approval, not before it. An approved application for one indication does not make an unapproved, differently labeled, differently dosed version of the same molecule lawful for any other use, and nothing about the Barth syndrome approval changes what the primary mitochondrial myopathy, heart failure, heart attack, and dry AMD trials actually found.