By Ahmed Aboulenein and Julie Steenhuysen
WASHINGTON, March 10 (Reuters) – The U.S. FDA approved leucovorin, a decades-old generic drug, to treat a rare genetic disorder which causes autism-like symptoms on Tuesday, but not for children with the broader diagnosis of autism it promised to help last year, citing a lack of data.
The approval to use leucovorin against folate deficiency is a significant step back from a September press conference when President Donald Trump and Health Secretary Robert F. Kennedy Jr. promoted the drug as a treatment for autism symptoms.
“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 GSK’s Wellcovorin, the branded version of leucovorin, based on a systematic review of the published literature on the topic rather than clinical trial data.
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 makes the drug, declined to comment on the review process.
The FDA’s update for the Wellcovorin label says that it studied 26 published case reports and reviews through 2024 and identified 27 patients who had received oral dosing of leucovorin. Of those, 24 had a range of improvements in symptoms including reduction in severity or number of seizures, improvements in motor function communication and or behavior.
LEUCOVORIN
Leucovorin, also known as folinic acid, is a form of folate, an essential B vitamin, or B9. It is used in people undergoing chemotherapy, but can be prescribed off-label for other uses.
The expanded approval allows all generic versions of the drug to include the new indication, the official said, and the FDA is encouraging drugmakers who make it to raise output.
FDA Commissioner Marty Makary said in September the agency had asked that drugmakers be prepared to ramp up production of leucovorin as a treatment for some autism patients.
Makary was speaking at a White House press conference where Trump linked autism to childhood vaccine use and the taking of popular pain medication Tylenol by women when pregnant.
During the press conference, Kennedy, who has promised to find the cause of autism, called the drug an “exciting therapy that may benefit large numbers of children who suffer from autism.”
The press conference had a profound effect, according to a recent study in the Lancet, which found that Tylenol use among pregnant women dropped in the following months, while prescriptions for leucovorin in children spiked by 71%.
LIMITED EVIDENCE IN AUTISM
The argument for wider use of leucovorin is built on small studies suggesting many children with autism have autoantibodies that block folate – a vitamin important for brain signaling – from entering the brain, causing a deficiency similar to 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.
(Reporting by Ahmed Aboulenein in Washington and Julie Steenhuysen in Chicago; Additional reporting by Deena Beasley in Los Angeles and Bhanvi Satija in London; Editing by Caroline Humer, Matthew Lewis and Alexander Smith)
