The U.S. Food and Drug Administration on March 10, 2026, approved the drug leucovorin for treatment of cerebral folate deficiency, an ultra-rare genetic condition affecting fewer than 1 in 1 million people in the United States. The agency explicitly declined to approve or endorse leucovorin for treating autism spectrum disorder or its symptoms in the broader population.
This decision followed a systematic review of available data and marked a direct reversal from statements made by administration officials in September 2025. On September 22, 2025, President Donald Trump appeared at a White House briefing alongside FDA Commissioner Marty Makary, HHS Secretary Robert F. Kennedy Jr., and other officials. They announced plans to expand access to leucovorin, describing it as a promising option for children with autism.
- Makary stated that the FDA was taking steps to change the drug’s label so it could be available to children with autism.
- He claimed that hundreds of thousands of kids could benefit.
- He suggested that 20 to 40 or even 50 percent of children with autism might have underlying folate-related issues that the drug could address.
The announcement tied into broader administration efforts to address what officials described as a tragic four-fold increase in autism diagnoses over two decades and to pursue treatments based on gold-standard science and common sense.
Leucovorin, a synthetic form of folinic acid (a type of vitamin B9), has long been used to counteract side effects of chemotherapy and to treat certain folate deficiencies. It is a generic drug, with a branded version marketed as Wellcovorin by GSK. The September 2025 announcement focused on cerebral folate deficiency (CFD), a neurological condition where folate cannot properly reach the brain due to transport issues. Symptoms of CFD include developmental delays, autistic features such as challenges with social communication and repetitive behaviors, seizures, and movement problems. FDA officials at the time noted an overlap between CFD symptoms and autism traits, and they initiated a process to approve leucovorin tablets specifically for CFD patients.
The initial plan drew criticism from autism researchers and medical organizations. Experts pointed out that evidence for leucovorin in autism came mostly from small studies, case reports, and off-label use. The American Academy of Pediatrics issued interim guidance against routine use of leucovorin in autistic children. The Coalition of Autism Scientists reviewed the data and concluded there was little scientific support for it as a safe and effective treatment for autism.
- In February 2026, the largest randomized trial on leucovorin for autism traits, published in 2024 in the European Journal of Pediatrics, was retracted due to data inconsistencies, statistical issues, and failure to replicate results.
- This retraction removed a key piece of evidence that had been cited in discussions around the drug.
FDA officials conducted a broader review starting with potential use in autism but narrowed the focus after examining the evidence. Senior officials, speaking anonymously in a briefing on March 9, 2026, stated that they lacked sufficient data to establish efficacy for autism more broadly.
- They emphasized that the strongest evidence, including larger effect sizes, applied only to the specific rare genetic form of CFD caused by mutations affecting folate transport into the brain.
- The approval covers leucovorin for this ultra-rare population in both children and adults, making it the first FDA-approved treatment for the condition.
- Officials noted that the agency remains open to further studies if companies pursue rigorous trials in the autism population, but current data does not support widespread use.
The March 2026 decision limits leucovorin to a tiny patient group, far short of the hundreds of thousands referenced in the 2025 White House statements. Autism affects an estimated 1 in 36 children in the U.S., based on CDC figures, with no known pharmacological cure and treatments focused on behavioral interventions and symptom management.
The administration’s initial promotion aligned with efforts to investigate environmental and biological factors in autism, including prior warnings about acetaminophen use in pregnancy and potential links to neurodevelopmental issues. However, the FDA’s final action rested on a data-driven assessment that rejected broader claims.
Experts expressed relief at the outcome. Pediatrician and autism researcher David Mandell stated:
“I am relieved the FDA did not approve leucovorin for autism,”
citing weak data and unpromising results from ongoing trials. Other specialists noted that promoting the drug without robust evidence risked:
- Giving false hope to families
- Diverting resources from proven approaches
The reversal highlights the importance of rigorous scientific standards in regulatory decisions, especially for vulnerable populations like children with autism. It prevents off-label expansion based on preliminary or flawed studies and ensures approvals match the actual evidence base.
The FDA’s evidence-based decision to limit leucovorin to cerebral folate deficiency protects patients from unproven treatments while leaving the door open for future research.
