A debate between Stealth BioTherapeutics and the FDA over a drug for Barth syndrome—a rare, often fatal childhood disease—could set an important example for other companies developing treatments for ultra-rare conditions. Currently, there are no approved therapies for Barth syndrome, which affects the mitochondria (the energy centers of cells) and can lead to muscle weakness, heart failure, and severe fatigue. Many children with this condition die before age five. Lindsay Marjoram, director of research for the Barth Syndrome Foundation, calls this case a key test for the FDA, showing that traditional approval methods may not work for extremely rare diseases. Now, the FDA is re-evaluating Stealth’s drug, elamipretide, after initially rejecting it in May. The company resubmitted its application, and the FDA accepted it last week, giving Stealth a clearer timeline to work with. Reenie McCarthy, CEO of Stealth BioTherapeutics, says this decision is crucial for the company’s survival and for patients relying on the drug. The FDA’s earlier rejection was surprising, especially after an advisory committee had voted in favor of the drug. The delay also strained the company financially, forcing layoffs and pausing other research projects. About 30 patients currently receive elamipretide through an expanded access program, a significant number given that only around 150 people in the U.S. have Barth syndrome. For these patients, losing access to the drug would be devastating. Barth syndrome severely impacts daily life, and while some patients undergo heart transplants, this only addresses one symptom—not the root cause. Elamipretide, however, targets the mitochondria directly, improving energy levels, mobility, and overall quality of life. Some babies even improved so much on the drug that they no longer needed heart transplants. The FDA has now set a decision date of September 26, much earlier than usual, recognizing the urgency of the situation. Stealth hopes for an accelerated approval based on muscle strength improvements, with plans for further studies after approval. This case highlights the challenges of approving drugs for ultra-rare diseases, where small patient populations make large clinical trials difficult. The FDA’s decision could influence how other companies approach approvals for similar conditions, offering hope for future treatments in this area.