The U.S. Food and Drug Administration on Tuesday approved Leucovorin, a decades-old generic drug, to treat a rare genetic disorder that causes autism-like symptoms. However, the agency did not approve it for children with the broader diagnosis of Autism, citing insufficient data to support that use.
The approval of leucovorin for folate deficiency represents a step back from statements made at a September press conference, when Donald Trump and Robert F. Kennedy Jr. promoted the drug as a potential treatment for autism symptoms.
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“So while we did originally approach this with a broad scope, as we looked through the scientific data, we ended up narrowing our scope to come to the strongest data evidence that we could find to support the approval,” a senior FDA official told reporters ahead of the approval announcement.
The U.S. Food and Drug Administration said it approved Wellcovorin, the branded version of leucovorin made by GSK, based on a systematic review of existing published studies rather than data from new clinical trials.
It was not feasible to conduct a randomized controlled trial due to the rareness of the disease, a second official said.
GSK, which no longer manufactures the drug, declined to comment on the review process.
According to an update from the U.S. Food and Drug Administration for the Wellcovorin label, the agency reviewed 26 published case reports and studies through 2024 and identified 27 patients who had received oral doses of leucovorin. Among them, 24 showed varying levels of improvement, including fewer or less severe seizures, as well as better motor function, communication, and behavior.
LEUCOVORIN
Leucovorin, also known as folinic acid, is a form of folate—an essential B vitamin (B9). It is commonly used in patients undergoing chemotherapy but may also be prescribed off-label for other conditions.
The expanded approval means that all generic versions of the drug can now include the new indication, an official said. The U.S. Food and Drug Administration is also encouraging manufacturers that produce the drug to increase their output.
Marty Makary said in September that the U.S. Food and Drug Administration had asked drugmakers to be ready to increase production of Leucovorin as a potential treatment for some autism patients.
Makary made the remarks during a White House press conference where Donald Trump suggested a link between Autism, childhood vaccines, and the use of the popular pain reliever Tylenol by pregnant women.
At the same event, Robert F. Kennedy Jr. who has pledged to identify the causes of autism—described the drug as an “exciting therapy that may benefit large numbers of children who suffer from autism.”
The press conference had a significant impact, according to a study published in The Lancet. The research found that Tylenol use among pregnant women declined in the months afterward, while prescriptions for leucovorin in children rose by 71%.
LIMITED EVIDENCE IN AUTISM
The case for broader use of Leucovorin is based on small studies suggesting that many children with Autism produce autoantibodies that block folate a vitamin essential for brain signaling from entering the brain. This blockage can lead to a deficiency similar to Cerebral Folate Deficiency (CFD).
But the data is limited and scientists have called for large clinical trials.
“Right now, we don’t have sufficient data to say that we could establish efficacy for autism more broadly,” the first official said on the FDA call.
“The review team did an amazing job really looking at the data for autism in general that’s available, and was really able to show why we don’t have the evidence at now for a broader approval.”
Doctors have already been prescribing leucovorin for autism off-label. The American Academy of Pediatrics does not recommend its routine use, citing a lack of evidence on benefits.
Researchers say leucovorin, used to treat some cancer patients on chemotherapy, has shown some promise in very small trials, but that large, randomized trials are still needed.
