The FDA last week denied approval for elamipretide, an experimental drug for Barth syndrome, despite dramatic improvements in heart function documented in patients with the rare genetic disorder that affects an estimated 150 people in the United States.
Jordan Karle's one-year-old son Jaylen represents a compelling case for the drug's potential. Born with heart failure due to Barth syndrome, Jaylen was given a 40% chance of survival at one day old. "The surgeon actually came in the room and told me like, look, do you want to sign a DNR for your son? He was like a day old and I immediately refused," Karle said.
Remarkable Clinical Response
At one month old in early 2024, Jaylen began taking elamipretide through a program available to critically ill babies. The results were striking: his heart function improved from 20% to normal levels within a month of starting treatment. "He was what we prayed for with this medication and we got that and we have gotten that for the past year," Karle said.
After more than a year on the drug, Jaylen is doing well without experiencing side effects, according to his mother. The transformation is particularly significant given the family's history with Barth syndrome - Karle's brother died at 18 months old with the condition in 2004, and a 16-year-old cousin survives with a new heart transplant.
Regulatory Setback and Pathway Forward
Despite an advisory committee's 10-6 vote recommending approval, the FDA denied the application for elamipretide approval. However, the agency did propose a pathway for accelerated approval, according to the drug manufacturer and the Barth Syndrome Foundation.
The Barth Syndrome Foundation's director called the FDA's decision "unconscionable" in a statement. The denial comes after what Congressman Mike Flood described as an "unusually long review" process in a March letter to the FDA calling for approval.
Urgent Access Concerns
Families now face the prospect of losing access to the drug entirely. Karle says she's been told that without approval, production of elamipretide could end in as little as six months, cutting off access for Jaylen and other patients currently receiving the treatment.
"We've been told that there's going to be change within the FDA for the rare disease community, and you're not showing that either," Karle said. "Not approving this medication is a death sentence to not just my son, but everyone living with" Barth syndrome.
Rare Disease Impact
Barth syndrome is a genetic condition that impacts the heart and almost exclusively affects boys. Karle learned she was a carrier at 23 weeks pregnant and received Jaylen's diagnosis before birth. The condition's rarity - affecting only around 150 people in the U.S. - makes it challenging to conduct large-scale clinical trials typical for drug approval.
Karle traveled to Washington, D.C., last fall to advocate before the advisory committee and met with Congressman Flood during the process. She emphasizes that Barth syndrome patients of all ages deserve access to elamipretide, not just critically ill infants currently eligible through compassionate use programs.
The case highlights ongoing challenges in rare disease drug development, where small patient populations and urgent medical needs often clash with traditional regulatory approval pathways.
