FDA doesn’t approve leucovorin for autism. What can it be used for?

Corrections and clarifications: Due to an editing error, a previous version of this story mischaracterized the scope of the new FDA approval for leucovorin.

The Food and Drug Administration has denied approving leucovorin as a treatment for autism, a significant pullback from how President Donald Trump and Health and Human Services Secretary Robert F. Kennedy Jr. earlier touted the drug.

Leucovorin, a drug prescribed to combat the effects of some cancer drugs, was approved for a label update on Tuesday, March 20, according to the Food and Drug Administration (FDA). Not for those with the broader diagnosis as endorsed by President Trump and Health and Human Services Secretary Robert F. Kennedy Jr., but for a rare condition called cerebral folate deficiency.

In a White House briefing on Sept. 22, Trump, Kennedy, and other officials made several announcements about plans to find and address an "answer to autism." The administration linked increased incidents of autism to Tylenol use in pregnancy, without evidence, and touted leucovorin to "treat" autism symptoms.

The administration has made repeated claims about its plans to find the "cause" for autism. Decades of medical and scientific consensus, however, indicate there is no singular source, including medication, that can be attributed to autism, which is probably the result of multiple contributing factors, including genetics.

Trump said in September that changing the label on leucovorin would give "hope to the many parents with autistic children that it may be possible to improve their lives.” And, while the new approval does mention "autistic features," it applies to a remarkably smaller demographic than originally presented months ago.

Here's what to know about what leucovorin does and who it is approved to treat.

What is leucovorin?

Leucovorin, also known as folinic acid, is a form of the essential B vitamin called a folate. It imitates the effect of folic acid in the body, which helps produce and maintain new cells, according to the Mayo Clinic and Drugs.com. Because of this, it is primarily prescribed to cancer patients to counteract the negative effects of chemotherapy drugs. It can also be used in tandem with other medications to more effectively target some types of cancer.

What did the FDA approve leucovorin for?

On Tuesday, March 10, the FDA approved the branded leucovorin pill called Wellcovorin for the treatment of cerebral folate deficiency (CFD) in the receptor 1 gene (FOLR1 deficiency), a rare genetic ​disorder that affects how folate is transported into the brain and can cause neuropsychiatric and developmental symptoms. CFD is an umbrella term; CFD-FOLR1 is the specific subtype named in the FDA approval.

The condition is believed to affect only about 1 in 1 million people, according to the FDA. It can cause some symptoms that are also common in people with autism, including difficulties with speech and motor skills, poor muscle tone and seizures.

The approval was based on a review of published literature and not on clinical trials, due to the rare nature of the condition.

"Today's approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today,” said FDA Commissioner Marty Makary in a press release. “This action may benefit some individuals with FOLR1- related cerebral folate transport deficiency who have developmental delays with autistic features," he added, marking the only reference to autism in the statement.

Previously, Makary told manufacturers in September to ramp up production ‌of the drug as treatment for some autism patients in anticipation of further FDA approvals.

"The announcement in September pertained to cerebral folate deficiency – of which cerebral folate transport deficiency is a genetic form – that is not the same thing as autism but can cause developmental delays with autistic symptoms," HHS press secretary Emily G. Hilliard told USA TODAY in a March 11 statement. "The FDA’s approval yesterday of this treatment for the genetic form builds on the initial announcement that the drug Leucovorin holds promise for those suffering from this condition."

What did Trump, RFK Jr. say about leucovorin and autism?

In the Sept. 22 White House briefing, Trump and his advisers promoted leucovorin as a "treatment" for autism, with Kennedy reportedly fast-tracking for FDA approval. Kennedy called the drug an "exciting therapy that may benefit large numbers of children who suffer from autism."

Experts and medical organizations like the American Academy of Pediatrics and the Child Neurology Society quickly took to combating both unsupported claims, but the press conference still had a near-instant real-world impact. In fact, a study published March 5 in the medical journal The Lancet found not only that emergency rooms across the U.S. tracked a 10% decrease in Tylenol orders for pregnant patients in the months following the briefing, but outpatient prescriptions for leucovorin in children rose 71%, at one point spiking over 90%.

What does science say about leucovorin and autism?

There is currently no widely accepted evidence supporting the therapeutic use of leucovorin in autistic people.

"Right now, we don't have sufficient data to say ​that we could establish ⁠efficacy for autism more broadly," FDA officials told Reuters. "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."

Some small studies have shown that some children with autism may experience cerebral folate deficiency or something similiar, meaning folate does not enter the brain correctly, impacting functions like speech and coordination. These findings are what piqued interest in leucovorin.

In the largest double-blind, placebo-controlled study of its kind, researchers in India studied folinic acid in a small group of children. One group of 39 kids was administered folinic acid, while a second group of 38 kids received a placebo. The November 2024 study found that children who received the drug had improved scores compared to the placebo group on the child autism rating scale, which is used to assess things like speech and nonverbal communication.

This study has since been retracted due to data errors, however.

"The evidence is very limited and very narrow, not definitive," Dr. Sara Rodrigues, executive director of Balanced Learning Center, a nonprofit serving autistic and neurodivergent people, told USA TODAY. "It’s important to recognize that treatment is really directed at underlying other needs, not the autism itself. None of the current research makes leucovorin an established or broadly recommended autism treatment."

Contributing: Ken Alltucker, USA TODAY; Reuters.