FDA Rejects Stealth BioTherapeutics' Elamipretide for Barth Syndrome, Company Plans Resubmission

Stealth BioTherapeutics has encountered a significant setback in its efforts to bring elamipretide to market for the treatment of Barth syndrome. The U.S. Food and Drug Administration (FDA) has issued a complete response letter, rejecting the company's application for the mitochondria-targeting peptide. Despite this setback, Stealth remains optimistic about the potential for accelerated approval and is taking steps to conserve resources for a resubmission.

Rejection Details and FDA Feedback

The FDA's decision comes after a prolonged review process that stretched over 16.5 months, significantly longer than the standard timeline for priority review. While rejecting the current application, the agency has provided Stealth with a potential path forward. The FDA has agreed to consider knee extensor muscle strength as a possible intermediate clinical endpoint to support accelerated approval.

This guidance from the FDA aligns with data from Stealth's phase 2 trial, which reportedly showed a more than 45% improvement in extensor muscle strength in patients treated with elamipretide. The company plans to leverage these results in its resubmission for accelerated approval.

Company Response and Strategic Adjustments

In response to the FDA's decision, Stealth BioTherapeutics has implemented strategic measures to conserve cash and refocus its efforts on resubmission:

1. The company has laid off 30% of its workforce to free up funds for the resubmission process.
2. Stealth plans to resubmit its application for accelerated approval, focusing on the knee extensor muscle strength data from its phase 2 trial.
3. The biotech emphasized that extensor muscle strength significantly correlated with improvements on the six-minute walk test, despite the trial missing its primary endpoint for this measure.

Regulatory History and Challenges

The road to approval for elamipretide in Barth syndrome has been fraught with challenges:

• Stealth initially presented data to the FDA in 2019.
• In 2021, the agency advised the company to conduct an additional phase 3 trial before seeking approval.
• Stealth submitted an application without the extra phase 3 data, resulting in a refusal-to-file letter from the FDA.
• In March 2024, the FDA accepted Stealth's resubmitted approval request for standard review, later granting priority review status.
• An FDA advisory committee voted 10-6 in favor of the filing in October 2024.
• The FDA delayed its decision multiple times before issuing the complete response letter.

As Stealth BioTherapeutics prepares for its next steps, the company remains committed to bringing elamipretide to market for patients with Barth syndrome, a rare genetic condition that primarily affects boys and can significantly reduce life expectancy due to heart failure and other complications.