Stealth BioTherapeutics‘ FORZINITY (elamipretide/SS-31) is a recently-approved therapy for Barth Syndrome, and Stealth is advancing it for several additional indications. Elamipretide is an antioxidant peptide compound that readily penetrates cell membranes and targets the inner mitochondrial membrane, where it binds reversibly to the key mitochondrial lipid cardiolipin. Cardiolipin is a phospholipid synthesized within the mitochondrial matrix that confers the distinctive folded shape to the inner mitochondrial membrane, helps organize the supercomplexes of the electron transport chain, and is crucial to its function. When a mitochondrion is damaged, cardiolipin moves to the outer mitochondrial membrane, where it triggers the selective destruction of the damaged organelle (mitophagy). Conversely, if the mitochondrion is damaged beyond repair, it will eject cariolipin and the key inner membrane protein cytochrome c outside itself, triggering “cellular suicide” (apoptosis).

Elamipretide stabilizes mitochondrial structure and sustains mitochondrial respiration, thereby improving electron transport chain function and ATP production in several animal models of age-related diseases, most notably renal disease, mitochondrial disorders, and heart failure. It achieves this in part by protecting cardiolipin from oxidative damage and maintaining its normal interactions with cytochrome c, thus preventing it from being ejected and triggering apoptosis.

Stealth adopted the WHO and United States Adopted Names Council (USAN) generic name “elamipretide” in 2016; it was previously known as MTP-131, SS-31, Bendavia, and Ocuvia.  

Barth Syndrome
Barth syndrome is a rare genetic disorder that afflicts roughly one in a million boys, with an estimated 130 patients in the United States. It is caused by mutations in the gene for Tafazzin (TAZ), an enzyme that catalyzes the final step in cardiolipin production. These mutations prevent the cell from producing enough cardiolipin for its needs and cause the cell to accumulate abnormal byproducts of cardiolipin synthesis, leading to mitochondrial dysfunction, early-onset cardiomyopathy, abnormal growth, skeletal muscle myopathy, and intermittent rounds of dangerously low neutrophil levels. Victims’ lives are very limited and generally cut short, and while doctors can help with some of the individual symptoms of the disorder, there are currently no specific treatments.

In March 2020, Stealth announced that FDA had granted Rare Pediatric Disease designation for elamipretide for the treatment of Barth syndrome.

In March 2021, scientists from Johns Hopkins and Stealth reported the results of TAZPOWER, a Phase II/III randomized, placebo-controlled crossover trial of elamipretide in Barth syndrome, followed by an open-label extension period. Because Barth is rare, the trial was small: just twelve subjects were randomized, and only eight subjects completed all 36 weeks of the extension study.

The primary endpoints for the trial proper were improvement in the 6-minute walk test and the Barth Syndrome Symptom Assessment (BSSA) scale; several secondary endpoints were specified for the extension study. Elamipretide failed on both fronts during the randomized phase, with no suggestion of an effect on either metric. However, both outcomes seemed to improve during the open-label extension, with walking test improvements of 16% at week 12 and 25% at week 36. Similarly, BSSA fatigue scores appeared to improve by 19% and 26% at the two time points, knee extensor strength by 30% and 42%, and there were nonsignificant nominal improvements on the Clinician Global Impression of symptom severity of 15% and 43%, respectively.

Stealth-affiliated scientists followed this up with a Phase III study comparing the TAZPOWER subjects with natural history controls. These controls were patients with Barth syndrome that Stealth recruited at the 2014, 2016, and 2018 Barth Syndrome Foundation International Conference and volunteered for a clinical phenotyping assessment by Stealth-affiliated scientists. The results showed that the improvements on primary and secondary metrics during the open extension in subjects on elamipretide were of similar magnitude when compared to natural history controls as they were when compared to their own baseline in the trial.

Following these two reports, Stealth filed a New Drug Application (NDA) for elamipretide in August 2021, primarily on the basis of the natural history control study.. In October 2021,  Stealth announced that it received a Refusal to File letter from FDA. FDA determined that Stealth’s application was insufficient for a substantive review, since TAZPOWER was negative during the randomized, double-blind period, and the open-label extension period was not controlled. Stealth objected that FDA did not consider the natural history control study, since FDA had granted elamipretide a Rare Pediatric Disease designation for the treatment of Barth, and FDA had previously issued guidance supporting the use of natural history control studies in rare disease drug development.

In June 2022, Stealth announced that FDA had agreed to meet with them to discuss a possible new NDA for elamipretide for Barth syndrome, and that they would be presenting new data collected at later time periods as part of the TAZPOWER extension study.

In July 2024, researchers affiliated with Stealth reported the 168-week open-label extension results of TAZPOWER. Elamipretide-treated patients sustained their improvement in the walk test (96.1 m of increased walking distance, similar to the 95.9 m (25%) improvement at week 36). BSSA fatigue scores partially reverted to baseline levels such that the difference was no longer significant. Subjects maintained their knee extensor strength gains from week 36. Balance scores appeared to have improved throughout the treatment period, from 71 at baseline to 77 at week 36 and 91 at week 168.

In October 2024, ahead of an independent advisory committee meeting, FDA staff issued a briefing document stating that FDA “does not believe that the available evidence establishes the effectiveness of elamipretide” for Barth syndrome, essentially repeating their earlier objections. In the event, however, the FDA Cardiovascular and Renal Drugs Advisory Committee voted 10 to 6 in favor of the revised NDA, concluding that elamipretide is effective for treating Barth syndrome.

In the following months, according to Stealth’s account of events, “FDA extended its review from January to April 2025, then missed its April 29 extended prescription drug user fee action date. The FDA also cited observations arising from a May 2025 CGMP surveillance inspection of a third-party manufacturing facility for elamipretide, although no specific deficiencies related to the elamipretide manufacturing process were identified.”

In May 2025, Stealth announced that FDA had “identified a potential path forward for elamipretide for the treatment of Barth syndrome.” Stealth would resubmit the elamipretide NDA, updated to include any additional safety data that they had collected since its most recent submission, and FDA would consider knee extensor strength as a potential intermediate endpoint to support accelerated approval on the basis that this endpoint significantly correlated with improvements on the six-minute walk test, which FDA recognizes as an indicator of clinical benefit.

In July 2025, FDA confirmed that the deficiencies at Stealth’s elamipretide manufacturing facility that they had previously cited had been resolved, and the facility remained in compliance, according to Stealth. In August, they resubmitted the NDA in accordance with FDA guidance.

On September 19, 2025, FDA granted accelerated approval for elamipretide to improve muscle strength in patients with Barth syndrome who weigh at least 30 kg. Stealth’s elamipretide will be sold under the brand name FORZINITY™. This is the first approval for any therapy for Barth.

Stealth continues to advance elamipretide for additional indications.