FDA Approves First Treatment for Barth Syndrome Amid Controversy

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Stealth BioTherapeutics' Forzinity (elamipretide), marking a significant milestone as the first-ever treatment for Barth syndrome, an ultra-rare genetic disorder affecting approximately 150 people in the United States.

Accelerated Approval Follows Tumultuous Regulatory Journey

Forzinity's path to approval has been fraught with challenges. The FDA initially rejected the drug in May 2025, citing concerns over its efficacy data. This decision came after a protracted 16.5-month review period and despite a favorable recommendation from an FDA advisory committee.

Following the rejection, Stealth BioTherapeutics resubmitted its application on August 15, 2025, this time seeking accelerated approval based on improvements in knee extensor muscle strength as an intermediate clinical endpoint. The FDA accepted the resubmission with unprecedented speed, setting a target review date of September 26, 2025 – significantly earlier than the typical six-month review period.

The accelerated approval was granted on September 19, 2025, ahead of the targeted date. This rapid turnaround has been attributed to mounting pressure from patient advocacy groups, physicians, and members of Congress, who urged the FDA to reconsider its stance on ultra-rare disease treatments.

Clinical Data and Approval Conditions

Forzinity's approval is based on data demonstrating improvements in knee extensor muscle strength, which the FDA deemed "reasonably likely to predict patient benefit." The drug is indicated for use in Barth syndrome patients weighing at least 66 pounds (30 kg).

As a condition of the accelerated approval, Stealth BioTherapeutics is required to conduct a post-approval randomized, double-blind, placebo-controlled trial to confirm that the observed improvements in muscle strength translate to meaningful clinical benefits for patients.

Implications for Ultra-Rare Disease Drug Development

The approval of Forzinity comes amid ongoing discussions about the FDA's approach to evaluating treatments for ultra-rare diseases. Earlier this month, the agency unveiled its Rare Disease Evidence Principles, a new framework aimed at streamlining the approval process for therapies targeting conditions affecting fewer than 1,000 Americans.

Dr. George Tidmarsh, director of the FDA's Center for Drug Evaluation and Research, stated, "The FDA remains committed to facilitating the development of effective and safe therapies for rare diseases and will continue to work diligently to help ensure patients with rare diseases have access to innovative treatments."

This approval may set a precedent for how the FDA handles future applications for ultra-rare disease treatments, potentially offering hope for expedited regulatory attention to other similar conditions.