The FDA’s commitment to timely drug approvals under the Prescription Drug User Fee Act (PDUFA) has been a cornerstone of its regulatory framework. Historically, the agency has maintained a high success rate in meeting its PDUFA goals; however, a handful of delays will typically occur each year for largely idiosyncratic reasons. Since 2021, when the FDA experienced delays due to challenges during the COVID-19 pandemic, the FDA has generally met or exceeded 90% of its review performance goals for new drug applications (NDAs) and biologics license applications (BLAs). However, recent regulatory upheaval at the FDA has prompted discussions of a potential decline in the previously reliable response rates and the implications for biotech companies and patients awaiting new therapies.
A recent example highlighting these concerns is the FDA’s delay in the approval decision for Stealth BioTherapeutics’ elamipretide, an investigational treatment for Barth syndrome—a rare genetic mitochondrial disease. Originally, the FDA set a PDUFA action date of January 29, 2025, for elamipretide. However, in January, FDA requested additional time to review additional data submitted by Stealth; FDA treated the submission as a major amendment, and the agency extended the deadline to April 29, 2025. As of that date, the FDA had not reached a decision, leaving patients and stakeholders in uncertainty. Despite such delays, the FDA, including Commissioner Makary, has re-emphasized that PDUFA dates are targets rather than strict deadlines and that occasional delays for good reason are not historically unusual. A spokesperson from the Department of Health and Human Services stated, “Any delays in drug approvals are the result of the FDA’s rigorous review process, which is designed to ensure that all medications are safe and effective for the American people.” This perspective underscores the agency’s prioritization of thorough evaluations over expedited decisions, especially for complex or novel therapies.
The delay of action on the Stealth NDA, in some respects, is a useful illustration of the agency’s intended careful approach. FDA had previously issued a complete response letter for an NDA for elamipretide in October 2021 after the company submitted the NDA following FDA’s refusal to file the application – a sign that the agency did not view it as sufficiently complete to permit substantive review. Back then, FDA asked for another Phase 3 trial, disagreeing with the company’s prior clinical strategy. And, in this review cycle, an advisory committee voted 10-6 to recommend approval of the drug after reviewing FDA’s arguments that the data submitted would not support either accelerated or full approval. Accordingly, the Stealth NDA may not be a typical application, and the delay of FDA action may not be the unwelcome bellwether of trends that it could be perceived to be.
For biotech companies, unanticipated delays can pose significant challenges, impacting financial planning and patient access to treatments. If frequent delays become a trend, company, investor and patient expectations may require significant adjustment. However, for now, a single data point among ten other timely approvals to date in 2025, coupled with encouraging language from the regulators, add up to an area for biotech board and management teams to keep an eye on as the year progresses, but likely not yet an acute concern notwithstanding broader industry concerns about FDA staffing.