- The FDA approved leucovorin for cerebral folate deficiency, not autism, on Tuesday.
- FDA Commissioner Dr. Marty Makary called it a significant milestone for rare cases.
- Parents of autistic children face challenges after leucovorin's limited approval and prescription surge.
ATLANTA — The prescription drug leucovorin is getting a label update, but it's not what the Food and Drug Administration suggested during a White House briefing in September, when officials touted the drug as a potential treatment for thousands of children with autism.
On Tuesday, the FDA approved the high-dose B vitamin — a treatment long used to counteract the side effects of chemotherapy — for cerebral folate deficiency in the receptor 1 gene, a genetic condition that's estimated to affect only about one in a million people. Fewer than 50 cases have ever been identified worldwide. FDA Commissioner Dr. Marty Makary called Tuesday's approval "a significant milestone" for patients with the condition.
But in September, Makary and US Health and Human Services Secretary Robert F. Kennedy Jr. indicated that the drug would be available to help many more children. Standing alongside President Donald Trump at a White House briefing, Kennedy said they had "identified an exciting therapy that may benefit large numbers of children who suffer from autism."
The update on leucovorin may hit some families of children with autism especially hard. At the September briefing — when Trump made unsupported claims about the painkiller Tylenol as a cause of autism and cautioned parents about getting too many vaccines for their kids — the president said changing the label on leucovorin "gives hope to the many parents with autistic children that it may be possible to improve their lives."
In the months since, leucovorin prescriptions surged, making the drug hard to find.
Drug approved for rare condition, not autism
With cerebral folate deficiency in the receptor 1 gene, a defect causes proteins that guide folate into the brain to malfunction. The result is normal levels of folate in the blood but not in the brain and nervous system, where it's important for thinking, speech and movement.
In an op/ed published in Politico and reposted on the White House website last fall, Makary said his agency would "approve prescription leucovorin as a treatment for children with cerebral folate deficiency and autistic symptoms."
Makary said in the televised briefing that between 20% and 50% of children with autism might make antibodies that block the proteins that help ferry folate into their brains – meaning some of the more severe symptoms of autism might be caused by an autoimmune condition.
Although he noted that leucovorin was not a cure for autism, Makary highlighted small studies showing that among children with folate deficiency and autism, it could improve speech for roughly 60%.
The Trump administration was making a bold move to expand the use of the drug, "opening the door to the first FDA-recognized treatment for autism," Makary and other HHS leaders wrote.
Senior FDA officials said in a briefing on Monday that while the data was strong enough to approve the use of leucovorin for the rare genetic cases of folate deficiency in the brain, they could not find enough evidence that it would help children with autism or other causes of cerebral folate deficiency.
"Right now, we don't have sufficient data to say that we can establish efficacy for autism more broadly," a senior agency official said.
"They really wanted a review of the data to support potential approval for some forms of autism. And in this case, the review was performed as was asked for, and the data that we had supported the approval for this specific indication," meaning the rare genetic form of the folate deficiency, another senior FDA official said.
The officials also noted that the largest randomized double-blind, placebo-controlled trial to test the drug in children with autism was recently retracted after errors were identified in the data reported in the study.
'The damage is done'
In the weeks after the September White House briefing, new prescriptions for leucovorin doubled, according to a study published this month in the Lancet medical journal.
Parents had trouble getting the drug, with some describing complicated searches for providers and pharmacies that could help. In some cases, people turned to unregulated over-the-counter folate supplements when they couldn't get the prescription version.
Study author Dr. Jeremy Faust, an emergency medicine physician at Brigham and Women's Hospital, told CNN last week that the evidence for leucovorin to treat autism is thin and didn't warrant a shift in practice, but he wasn't surprised to see prescriptions spike.
"I think that the White House lectern is a very powerful place, and people do listen to our leaders, even though RFK says things like 'don't take medical advice from me,'" Faust said.
News of the FDA's shift on leucovorin was a blow to some parents, including Meagan Johnson, a mom in Pflugerville, Texas, who recently struggled to find the medication for her 3-year-old son Jack.
"I'm upset and more than just mad, I'm hurt," Johnson said on Tuesday.
"I'm frustrated with the administration. I'm tired of them coming out and prematurely saying things without the information to back it."
"I feel like I just fought really hard," to get the drug for her son. Now, she said she wonders if his doctor — or any doctor — will continue to prescribe it. She also worries that insurance may stop covering it.
