FDA Rejects Stealth BioTherapeutics’ Rare Disease Drug but Leaves Door Open for Accelerated Approval

On May 29, 2025, the FDA rejected Stealth BioTherapeutics' application for elamipretide, a drug targeting the ultra-rare genetic disorder Barth syndrome24.

The FDA issued a complete response letter after a 16.5-month priority review that was delayed multiple times, citing study data concerns24.

Despite the rejection, the FDA indicated willingness to consider accelerated approval if Stealth can demonstrate benefits using knee extensor muscle strength as an intermediate clinical endpoint24.

Stealth's phase 2/3 trial missed its primary endpoints, but the company says a separate phase 2 trial showed more than 45% improvement in extensor muscle strength2.

Barth syndrome is a rare metabolic disorder, nearly always affecting boys, with symptoms including heart issues, muscle weakness, and immune dysfunction, with a U.S. patient population estimated at around 15021.

Because of the regulatory setback, Stealth announced plans to resubmit for accelerated approval, but also laid off 30% of its staff to conserve cash2.

A recent FDA inspection at a third-party manufacturing site played a role in the regulatory delay, though not in the ultimate rejection3.

Sources:

1. https://www.statnews.com/pharmalot/2025/05/29/novo-wegovy-ozempic-weight-diabetes-lilly-stealth-biotech-pharma-rare-disease-fda-moderna-vaccine-hhs-bird-flu-antibiotics-gonorrhea-alcon-eyes-pubmed-germany/

2. https://www.fiercebiotech.com/biotech/stealth-bombs-fda-receiving-rejection-twice-delayed-filing-and-laying-staff

3. https://www.prnewswire.com/news-releases/stealth-biotherapeutics-announces-path-forward-despite-disappointing-delay-for-ultra-rare-barth-syndrome-302467718.html

4. https://endpts.com/fda-rejects-stealths-rare-disease-drug-but-offers-potential-for-accelerated-approval/