⚕️FDA Walks Back Autism Hopes for Leucovorin, Citing Insufficient Evidence After Earlier Claims

Agency clarifies that the generic drug will be approved only for an ultra-rare genetic disorder linked to cerebral folate deficiency, not as a treatment for autism.

WASHINGTON | The U.S. Food and Drug Administration said this week that current scientific evidence does not support the use of the generic drug leucovorin as a treatment for autism, marking a significant shift from earlier statements by top federal health officials who had suggested the medication could benefit large numbers of children with the condition.

Senior FDA officials told reporters that the agency’s latest decision reflects a commitment to approving therapies only when clear clinical evidence of safety and effectiveness exists. Instead of approving leucovorin for autism-related conditions, regulators authorized the drug for a rare genetic disorder known as FOLR1-related cerebral folate transport deficiency, a condition that affects fewer than one in a million people.

The move effectively narrows the scope of the drug’s regulatory approval after months of public discussion surrounding its potential broader neurological benefits.

Earlier Claims Raised Expectations

Interest in leucovorin surged last year after Health and Human Services Secretary Robert F. Kennedy Jr. and FDA Commissioner Marty Makary publicly discussed its possible role in helping children with autism who experience cerebral folate deficiency, a condition in which the brain is unable to properly absorb folate, a vitamin essential for neurological development.

At a September news conference alongside President Donald Trump, Makary said preliminary research suggested the drug could help “hundreds of thousands” of children with autism symptoms.

One frequently cited study indicated that roughly two-thirds of children with autism and chronic folate deficiency experienced improvements, particularly in verbal communication.

But federal regulators now say that the available data remains too limited to support approving the drug as a treatment for autism more broadly.

“Right now, we don’t have sufficient data to establish efficacy for autism,” one senior FDA official said during a briefing with reporters. “That evidentiary standard was met only for this specific genetic form of cerebral folate deficiency.”

Rare Disease Approval Moves Forward

Instead, the FDA approved leucovorin for patients with FOLR1-related cerebral folate transport deficiency, a rare neurological disease caused by a mutation in the FOLR1 gene.

The disorder disrupts the brain’s ability to transport folate into cells, often leading to severe developmental delays, seizures, movement disorders, and neurological impairment.

Under the new approval, the drug can be prescribed to both children and adults diagnosed with the condition.

Makary said the decision could still help certain patients who experience developmental symptoms associated with the genetic disorder.

The treatment “may benefit individuals with FOLR1-related cerebral folate transport deficiency who have developmental delays with autistic features,” Makary said in a statement.

Retraction of Key Study Complicated Approval

FDA officials acknowledged that the agency initially reviewed evidence suggesting leucovorin might improve autism symptoms in some patients.

However, a randomized controlled trial often cited as key evidence was recently retracted by the European Journal of Pediatrics after errors were identified in its reported results.

That development significantly weakened the scientific case for approving the drug as a treatment for autism.

Regulators said the FDA ultimately relied on a systematic literature review when evaluating leucovorin’s effectiveness for the rare genetic disorder rather than a traditional randomized trial, which would be difficult to conduct given the condition’s extremely small patient population.

Off-Label Use Remains Possible

Although the FDA did not approve leucovorin for autism treatment, doctors are still allowed to prescribe the drug “off-label” if they believe it may benefit certain patients.

Medical experts caution that such decisions should be made carefully and in consultation with healthcare providers, given the limited evidence currently available.

The FDA also said it remains open to reviewing new clinical research should pharmaceutical companies or research institutions pursue larger studies examining the drug’s potential neurological benefits.

Supply Concerns and Rising Demand

The debate over leucovorin’s possible autism benefits triggered a surge of interest among families and clinicians, raising concerns about potential supply shortages.

In November, the American Society of Health-System Pharmacists reported limited availability of the drug following the earlier public statements about its potential uses.

FDA officials now say they do not currently consider leucovorin to be in shortage, though they are monitoring demand and coordinating with manufacturers to ensure adequate supply.

“If demand continues to increase, we are in discussions with additional manufacturers to increase production and consider importation options if necessary,” one official said.

A Reminder of the FDA’s Evidence Threshold

The episode underscores the delicate balance federal regulators face when evaluating emerging treatments for complex neurological conditions such as autism.

While early research sometimes sparks optimism, FDA officials emphasized that therapies must ultimately meet strict scientific standards before receiving approval for widespread use.

The agency said it will continue encouraging further research into treatments that could improve outcomes for children with autism and related neurological disorders.

But for now, leucovorin’s officially approved role will remain narrowly focused on a rare genetic disorder linked to cerebral folate deficiency, rather than the broader autism spectrum.

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-- By Cierra Jacobs

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