The FDA has approved expanded use of leucovorin calcium tablets (Wellcovorin, GSK) for treatment of adults and children with cerebral folate deficiency and a confirmed variant in the folate receptor 1 gene (CFD-FOLR1), an ultra-rare brain disorder that can resemble autism.

The agency did not approve the drug for autism, however, despite the Trump administration’s announcement at a White House press briefing last September that it would. 

At the September briefing, US Department of Health and Human Services Secretary Robert F. Kennedy, Jr said his agency had identified leucovorin calcium as “an exciting therapy” that may benefit children with autism and that he had asked the manufacturer to submit a supplemental new drug application to update the label for that indication.

Yet in this week’s approval announcement, FDA Commissioner Marty Makary, MD, MPH, appeared to walk back that notion — saying only that leucovorin “may benefit” some individuals with FOLR1-related CFD who have “developmental delays with autistic features.”

Various media reports indicate that during a briefing with reporters, a senior FDA official stated that the agency does not currently have sufficient evidence to establish the efficacy of leucovorin for autism more broadly. 

A Welcome Announcement 

This is “an extremely welcome announcement from the FDA,” Helen Tager-Flusberg, PhD, professor emerita at Boston University in Massachusetts, founder of the Coalition of Autism Scientists, told Medscape Medical News.

Tager-Flusberg said she strongly supports the FDA’s move to walk back earlier suggestions that leucovorin is an effective treatment for autism.

“I’m glad to see that they are going with what the evidence tells us, which is that there is no strong evidence available that leucovorin is an effective treatment for autism,” said Tager-Flusberg, who also is a founding member of the newly formed Independent Autism Coordinating Committee, which was established to push back against what its members view as dangerous claims by the current administration about autism’s causes and treatments. 

Last week, a study published in The Lancet showed new prescriptions for the drug in children ages 5-17 jumped by 71% following the September briefing. 

Tager-Flusberg added that, since the briefing, clinicians have been fielding questions about leucovorin and correcting patients’ misconceptions about the drug, often having to explain why they won’t prescribe it instead of helping families pursue more productive options.

CFD-FOLR1 affects an estimated 1 in 1 million people. Leucovorin is the first approved treatment for the disorder, the agency said. Approval was based on a systematic review of the published literature on the topic, including published case reports with patient-level information, as well as mechanistic data.

“The FDA collaborated with GSK, the new drug application holder of Wellcovorin, on a process to update the labeling to include the essential scientific information needed for the safe and effective use of the drug for adults and pediatric patients with CFD-FOLR1,” the FDA explained in the announcement. 

Potential side effects associated with leucovorin include pruritus, rash, urticaria, dyspnea, rigors, and impaired thermoregulation, as well as anaphylaxis, the FDA said.