Stealth BioTherapeutics Faces Uncertain Future as FDA Denies Reconsideration for Rare Disease Drug

Stealth BioTherapeutics, a company focused on developing treatments for rare genetic disorders, is facing significant challenges following the U.S. Food and Drug Administration's (FDA) decision to deny reconsideration of its complete response letter for elamipretide, an investigational treatment for Barth syndrome.

FDA Rejection and Resubmission Requirements

The FDA's recent denial of Stealth's request to reconsider its complete response letter has left the biotech company in a precarious position. Despite acknowledging that there are no safety concerns and no new efficacy data required on a pre-approval basis, the agency is directing Stealth to resubmit its drug application.

This decision comes after a series of setbacks for the company, including:

• A complete response letter issued by the FDA in May, following more than 16 months of priority review
• Multiple FDA delays in the review process
• A split advisory committee vote that ultimately favored approval

Stealth BioTherapeutics now faces the prospect of submitting its third new drug application, a process that could take more than two years for the agency to review a data set comprising just 12 patients.

Impact on Stealth BioTherapeutics and Patients

The ongoing regulatory challenges have placed significant strain on Stealth BioTherapeutics, both financially and operationally. Key developments include:

• A 30% reduction in staff following the May rejection, aimed at conserving cash for a potential resubmission
• Questions about the company's viability and ability to continue providing the drug to patients
• Concerns about maintaining drug availability for the vulnerable Barth syndrome community

Christopher Pena, a patient with Barth syndrome who has been taking elamipretide, expressed concern about potentially losing access to the treatment, stating, "It's helped a lot. Before, I couldn't go anywhere and keep up with my friends."

Clinical Data and Expert Opinions

Elamipretide, a mitochondria-targeting peptide, has shown mixed results in clinical trials:

• The drug failed to meet a six-minute walk test endpoint in a clinical trial
• The FDA previously deemed data on muscle changes from baseline as "exploratory and uninterpretable"
• Despite these concerns, the independent advisory committee voted 10-6 in support of elamipretide for Barth syndrome

Dr. Brian Feingold, a pediatric cardiologist who has cared for nine patients with Barth syndrome, advocated for the drug's approval, citing its "excellent safety profile" and the challenges of conducting large-scale trials for such a rare condition.

As Stealth BioTherapeutics evaluates its options, the fate of elamipretide and the company's future remain uncertain. The ongoing regulatory hurdles highlight the complexities of drug development and approval for ultra-rare genetic disorders, where patient populations are limited and traditional clinical trial designs may not be feasible.