FDA approves elamipretide (Forzinity) for Barth syndrome

The US FDA granted accelerated approval to elamipretide (brand name Forzinity) in September 2025 as the first-ever approved therapy for Barth syndrome (BTHS). Barth syndrome is a rare X-linked mitochondrial disorder characterized by cardiomyopathy, myopathy, neutropenia, and high infant mortality. Elamipretide is a synthetic tetrapeptide that targets the inner mitochondrial membrane - a milestone for peptide therapeutics in rare diseases. Here I break down the clinical evidence, mechanism of action, and what this means.

Key facts at a glance

• The FDA granted elamipretide (Forzinity) accelerated approval for Barth syndrome - the first approved treatment for this condition.
• The peptide targets cardiolipin in the inner mitochondrial membrane, stabilizing cellular energy production.
• Approval is based on the Phase 3 TAZPOWER trial, which showed improved knee extensor muscle strength as an intermediate clinical endpoint.
• The approved dose is 40 mg subcutaneously once daily for patients weighing at least 30 kg.
• A confirmatory Phase 3b/4 trial (4TAZPower) is ongoing to verify long-term efficacy.

What is Barth syndrome and why has it been so hard to treat?

Barth syndrome (BTHS) is a rare X-linked metabolic disorder that almost exclusively affects boys. It is caused by mutations in the TAFAZZIN (TAZ) gene, which encodes an acyltransferase required for cardiolipin (CL) biosynthesis^[7]. Cardiolipin is a specific mitochondrial phospholipid that stabilizes the assembly of supercomplexes involved in oxidative phosphorylation^[3]. Without functional cardiolipin, cellular energy production is severely impaired, leading to cardiomyopathy, generalized muscle weakness, growth delay, and recurrent infections due to neutropenia. Before elamipretide, no causal therapy existed - only symptomatic management.

How does elamipretide work - and what does this have to do with peptides?

Elamipretide is a linear tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH₂ (Dmt = dimethyltyrosine). It belongs to the Szeto-Schiller peptide family and is the first mitochondria-targeted peptide to receive FDA approval. The mechanism: elamipretide binds to cardiolipin in the inner mitochondrial membrane and stabilizes its structure^[5]. This slows the degradation of cardiolipin via the intermediate monolysocardiolipin, keeps respiratory supercomplexes intact, and allows the cell to produce more ATP. This makes elamipretide a textbook example of how peptides can act as highly specific therapeutics at the subcellular level.

What do the clinical data from the TAZPOWER trial show?

The approval is based on the TAZPOWER trial, a randomized, double-blind, placebo-controlled Phase 3 study over 28 weeks followed by a 168-week open-label extension (OLE)^[1]. Of 12 enrolled subjects, 10 entered the OLE and 8 completed the week-168 assessment^[4]. The FDA based its accelerated approval on improved knee extensor muscle strength measured by handheld dynamometry as an intermediate clinical endpoint^[5][7]. OLE data showed significant improvements in muscle strength, fatigue, and cardiac function over 168 weeks^[7]. Importantly, exact p-values and effect sizes from the randomized phase are not reported in detail in publicly available sources - the evidence is limited due to the tiny sample size (n=12).

Who is Forzinity approved for and what is the dosing?

Elamipretide (Forzinity) is approved to improve muscle strength in individuals with Barth syndrome weighing at least 30 kg^[5]. The dose is 40 mg administered subcutaneously once daily^[1][5]. The most common adverse events were injection-site reactions^[1]. This is an accelerated approval, meaning the manufacturer is required to confirm clinical benefit in a post-marketing study.

What studies are ongoing - and what comes next?

A confirmatory Phase 3b/4 trial called 4TAZPower (NCT07531251) is currently underway. It is a randomized, double-blind, placebo-controlled study over 72 weeks designed to confirm the efficacy of elamipretide in genetically confirmed Barth syndrome^[6]. The primary objective is to confirm the benefit underlying the accelerated approval. No information on other therapeutic approaches (gene therapy, other compounds) for Barth syndrome was found in the evaluated sources - the pipeline remains very thin.

What does this approval mean for peptide therapeutics?

This approval is noteworthy for several reasons. First, it is the first approved drug for Barth syndrome - a patient population that previously had no pharmacological option. Second, it is the first mitochondria-targeted peptide to receive FDA approval, validating the potential of peptides as therapeutics for rare, genetically driven metabolic disorders. Third, it demonstrates how accelerated approval pathways work for rare diseases with high unmet medical need - with the requirement to confirm efficacy post-marketing. For a deep dive into elamipretide's mechanism, trial data, and regulatory status, check out my SS-31 peptide profile in the library. The glossary also explains terms like cardiolipin and subcutaneous injection.

Not medical advice: This article is for informational purposes only and does not replace professional medical advice. Consult a specialist physician for questions about Barth syndrome treatment.