FDA Says It Will Review Stealth’s Application for Barth Syndrome Treatment

Rare Daily Staff

The U.S. Food and Drug Administration said it will review Stealth BioTherapeutics’ New Drug application for elamipretide for the treatment of the rare and deadly condition Barth syndrome.

The decision follows a protracted fight between the agency and company and patient advocates over whether Stealth had studied the drug in an adequate number of patients for it to review its application, let alone approve it. That’s despite the fact that the principal investigator of the Stealth study has said that she’s screened every patient in North America that fits the clinical trial inclusion criteria. Previously, the agency notified the company it would not consider its application.

The willingness of the agency to now consider approving elamipritide follows ongoing efforts by the company and patient advocates to get the agency to review Stealth’s application. In December 2023, the Barth Syndrome Foundation delivered a petition with nearly 20,000 signatures to the FDA asking the agency to consider approving elamipretide. That was the most visible of a long list of efforts started in 2019 that included letter writing campaigns, meetings between the FDA and Stealth, and nearly 200 meetings with legislators.

Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities often leading to heart failure and reduced life expectancy, recurrent infections, muscle weakness, and delayed growth. Barth syndrome occurs almost exclusively in males and is estimated to affect one in 200,000 to 400,000 individuals worldwide. There are currently no U.S. Food and Drug Administration or European Medicines Agency-approved therapies for patients with Barth syndrome.

Elamipretide is a peptide that targets the inner mitochondrial membrane where it binds to cardiolipin, which plays an essential role in energy conversion within cells. Elamipretide is also in development for primary mitochondrial myopathy, with pivotal data from a fully-enrolled phase 3 trial expected in late 2024.

Stealth first submitted a new drug application to the FDA at the end of August 2021 despite the agency’s recommendation that additional controlled data be generated to support its review. Neither the FDA nor the company had been able to identify a feasible trial design due to the ultra-rare nature of this disease. At the time, though, the agency refused to consider the application because it said the drug had not been studied in enough patients.

The submission was based on results from the SPIBA-001 phase 3 Retrospective Natural History Control Trial, which compared data from the open-label portion of the TAZPOWER phase 2/3 clinical trial to matched natural history controls. SPIBA-001 met its primary and most secondary endpoints, demonstrating elamipretide-mediated improvements in assessments of exercise tolerance, strength, and cardiac function that are unexpected in the natural course of this progressively debilitating disease.

While the FDA has now agreed to review the application, it denied priority review designation for elamipritide. That means the review process will be longer than the company expected, culminating in a decision early next year rather than this fall as it had anticipated.

While the Barth Syndrome Foundation expressed gratitude that the FDA had listened to the patient community and will review the application, it acknowledged that more challenges are ahead.

“This is not the finish line. Now that the FDA has agreed to review the NDA, we must remain committed to ensuring that it receives a full, fair, and equitable review,” the post said. “We don’t yet see FDA’s full acknowledgement of how serious and life-threatening Barth syndrome is. Treatment can significantly improve the lives of those living with Barth syndrome, and today there are no treatments specific for Barth syndrome.”

Photo: Kate McCurdy, board chair of the Barth Syndrome Foundation, delivers petition to the FDA in December 2023.