Forzinity (Elamipretide) wins accelerated approval-the first FDA-approved therapy for Barth syndrome

The U.S. Food and Drug Administration (FDA) have granted accelerated approval to Forzinity (Elamipretide HCl) developed by Stealth Biotherapeutics as the first approved treatment for Barth syndrome. This approval covers adults and children weighing at least 30 kg. Previously there was no disease-specific therapy available. The decision was based on evidence showing improvement in muscle strength, which the FDA considered “reasonably likely to predict” broader clinical benefit which means the FDA believes that despite of non-significant primary endpoint, the other effect strongly suggests real clinical benefits will follow however it still requires a confirmatory trial to prove it. Forzinity is a once-daily subcutaneous injection and has received accelerated approval along with a rare pediatric disease priority review voucher.

What is Barth syndrome?

Barth syndrome is an ultra-rare, inherited mitochondrial disorder caused by mutations in the TAZ gene. This genetic defect disrupts the production of cardiolipin, a critical component of the inner mitochondrial membrane. Without proper cardiolipin, mitochondria cannot generate energy efficiently.

Children born with Barth syndrome present with cardiomyopathy (weak heart muscle), neutropenia (low white blood cell counts), growth delay, and severe skeletal muscle weakness. Many patients struggle with exercise intolerance and are at risk of infections due to weakened immunity. It is estimated that only around 150 people in the United States and fewer than 300 worldwide have been diagnosed, however it is believed that the condition is underreported. Till date there was no FDA-approved treatment for this disorder, and care mostly depends on supportive measures such as infection prevention, heart medications, and nutrition support.

Elamipretide: origin, class, and mechanism

Elamipretide (formerly known as MTP-131 or Bendavia) is a mitochondria-targeted tetrapeptide discovered and developed by Stealth Biotherapeutics. It belongs to a novel drug class often described as mitochondria-targeted therapeutics or mitochondria-protective peptides.

Its discovery came from efforts to design small peptides that could cross the mitochondrial membrane and interact directly with lipids that control energy production. Researchers identified cardiolipin, a phospholipid found only in mitochondria, as a key target.

Elamipretide works by binding to cardiolipin in the inner mitochondrial membrane. This stabilizes the structure of mitochondria, reduces production of harmful reactive oxygen species, and improves the efficiency of oxidative phosphorylation, the process that generates ATP (energy) inside cells. In Barth syndrome, where faulty cardiolipin leads to fragile and dysfunctional mitochondria, Elamipretide may help restore balance and improve muscle cell function. This mechanism targets the root problem of the disease rather than treating the symptoms.

 Clinical Evidence

The pivotal evidence for Forzinity (Elamipretide) came from the TAZPOWER study programme (NCT03098797), a two-part clinical program in genetically confirmed Barth syndrome patients aged 12 years and older. In Part 1, a randomized, double-blind, placebo-controlled crossover trial, participants received 40 mg Elamipretide subcutaneously once daily for 12 weeks and then crossed over after a washout. The primary endpoints were change from baseline in the 6-minute walk test (6MWT) and the Barth Syndrome Symptom Assessment–Total Fatigue (BTHS-SA Fatigue) score. While this phase did not achieve statistical significance on its primary endpoints in the overall intent-to-treat group, signals of benefit were seen in some patients, particularly improvements in muscle strength and functional capacity.

All participants were then eligible to continue in an open-label extension (OLE) lasting up to 168 weeks. Ten patients entered the OLE, and eight completed it. Over this period, Elamipretide was generally well tolerated, with the most common adverse events being mild-to-moderate injection site reactions. Importantly, sustained functional gains were observed: by week 168, patients improved their 6MWT distance by an average of 96 meters from OLE baseline and reported consistent reductions in fatigue on the BTHS-SA scale. Biomarker improvements, particularly normalization of the monolysocardiolipin to cardiolipin (MLCL:CL) ratio, were noted and correlated with functional outcomes, supporting Elamipretide’s mechanism of stabilizing mitochondrial membranes. These results, though limited by the very small sample size and the open-label design, provided the FDA with enough evidence to grant accelerated approval, with the requirement for a confirmatory randomized trial to verify clinical benefit.

Safety Profile

The most common side effects reported with Elamipretide are injection site reactions such as redness, pain, or swelling. Some patients experienced more serious side effects, which will be carefully tracked in post-marketing studies.