Fda Backs Away From Rfk Jr.’s Claims About Drug’s Promise For Autism Patients

The Food and Drug Administration does not have sufficient evidence to back the use of the generic drug leucovorin for treating children with autism, two senior agency officials told reporters Monday.

The agency’s announcement represents a major change in its view since Health Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary touted the drug, also known as folinic acid, as a promising therapy that could benefit some children with autism at a September news conference with President Donald Trump.

Then, Makary had said the drug would help “hundreds of thousands” of kids and that one study had shown that among kids with autism and chronic folate deficiency, “two-thirds of kids with autism symptoms had improvement and some marked improvement.” Folate deficiency doesn’t allow folate, an important vitamin for the brain, to get into the brain cells, Makary explained at the time.

On Tuesday, the agency approved the drug not for autism but for a form of cerebral folate deficiency that is a hallmark of an ultra-rare disease.

Makary said in a statement that the approval “may benefit some individuals with FOLR1- related cerebral folate transport deficiency who have developmental delays with autistic features.”

The FDA had originally planned to grant fast-track approval to the drug, which is a form of a B vitamin, to treat kids with cerebral folate deficiency and autistic symptoms, Makary explained at the September news conference and in a POLITICO Magazine opinion piece he co-authored with National Institutes of Health Director Jay Bhattacharya and Centers for Medicare and Medicaid Services Administrator Mehmet Oz.

While they emphasized in the opinion piece that leucovorin “is not a cure for autism,” they said there was evidence the drug, which is now used to treat cancer and anemia patients, could help some children with autism improve their verbal communication.

Scientists had cautioned that, while leucovorin could be promising for a subset of autism patients, the current data supporting its use is limited and more research is required.

The drug is now the only FDA-approved treatment for a disease affecting fewer than 1 in a million people that is caused by a cerebral folate transport deficiency. The FDA approved the drug Tuesday for use in both children and adults.

Folate is a vitamin essential for brain health. The disease is related to a defect in one gene called the CFD-FOLR1 gene, the first senior agency official said, speaking to reporters only on condition that their name would not be reported. The disease can often cause severe developmental delays, movement disorders, seizures, and other serious neurological complications, according to the Department of Health and Human Services.

“Right now, we don't have sufficient data to say that we can establish efficacy for autism more broadly, but it'll be up to patients to talk with their physicians to see if that might be right for them” for off-label use, the official said.

“I think this points out that we really are committed, at the FDA, to approving products based on a certain evidentiary standard, and that was met with this specific genetic form of cerebral folate deficiency,” the official said. The agency is open to submissions and interest from companies in studying the drug for use in autism, the official added.

The FDA, which used a systematic literature review to approve the existing drug to treat the ultra rare disease, did examine whether leucovorin could be used to treat autism, the second official, who also would only speak to reporters after they agreed not to report the official’s name, said.

But the data more clearly supported the drug’s efficacy against the ultra rare disease, the official added.

Pressed on why FDA Commissioner Makary sounded so optimistic about leucovorin’s potential to treat autism in September, the first official said that a randomized controlled trial that was cited initially in support of that potential use was recently retracted.

The European Journal of Pediatrics withdrew that study earlier this year after errors were identified in some of the reported results.

For its rare disease approval, the FDA relied on the literature review for data generation instead of a randomized controlled trial, which is the usual standard, because the latter would have been challenging to do since so few people have the disease, the second official said.

The American Society of Health System Pharmacists reported a shortage of leucovorin in November, after Kennedy and Makary spoke about the drug’s potential to treat autism.

But the FDA officials who briefed reporters Monday said they don’t consider the drug to be in shortage.

“If demand continues to increase, we are in discussion with other companies to allow for importation and also for existing manufacturers to increase their manufacturing,” the second FDA official said.