By Ahmed Aboulenein and Julie Steenhuysen
WASHINGTON, March 10 (Reuters) – The U.S. FDA on Tuesday approved leucovorin, a decades-old generic drug, for use against an ultra-rare disorder called cerebral folate deficiency, but not for children with the much broader diagnosis of autism that it had promised last autumn to help, citing a lack of data.
The approval for the rare genetic disorder, which causes autism-like symptoms, is a significant step back from the government’s 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 U.S. Food and Drug Administration official told reporters on a press call ahead of the approval announcement.
The FDA 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.
The agency said there were between 20 and 50 case studies of people with the disorder but did not provide details of the review’s scope.
LEUCOVORIN
Leucovorin, also known as folinic acid, is a form of folate, an essential B vitamin, or B9. It is currently used in people undergoing chemotherapy but can be prescribed off-label for other uses.
GSK no longer makes the drug but the expanded approval allows all generic versions of the drug to include the new indication, the official said, and the agency is encouraging drugmakers who produce it to increase production.
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 an extraordinary 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 months following the press conference 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; Editing by Caroline Humer and Matthew Lewis)
