The agency also pointed to the use of Tylenol and other acetaminophen products during pregnancy as being potentially linked to neurological and developmental defects in children, following a press conference Monday in which President Donald Trump did the same.
The FDA on Monday took the highly unusual step of initiating the reapproval of GSK’s Wellcovorin, seeking to bring the drug back after 25 years off the market as a potential treatment for autism symptoms.
The regulator has kicked off the approval process for Wellcovorin—a branded version of leucovorin—for cerebral folate deficiency (CFD), a condition characterized by low levels of folate in the brain despite having normal blood concentrations. The FDA linked CFD to “developmental delays with autistic features” as well as seizures and motor problems.
To back its claims up, the FDA on Monday said it has conducted a “systematic analysis” of studies from 2009 to 2024, including patient-level information and “mechanistic data,” which together support the benefit of leucovorin in patients with CFD. Still, in its own press announcement on Monday, the Department of Health and Human Services conceded that leucovorin “is not a cure for ASD [autism spectrum disorder] and may only lead to improvements in speech-related deficits for a subset of children.”
Wellcovorin was originally approved in 1983 to help counteract the toxic effects of the chemotherapeutic drug methotrexate, as well as of overdoses from folic acid antagonists. GSK eventually stopped marketing the drug and pulled it from the market in 1997. Leucovorin, its active ingredient, is available in the U.S. as a generic.
The FDA is working with GSK to “broaden” Wellcovorin’s label, George Tidmarsh, director of the agency’s Center for Drug Evaluation and Research, said in a statement on Monday. For its part, the pharma has also expressed intent to file a supplemental application for Wellcovorin’s in CFD.
Aside from bringing back Wellcovorin, the regulator on Monday also initiated a label update for Tylenol and other similar acetaminophen products “to reflect evidence” indicating that use in pregnancy could be linked to an “increased risk of neurological conditions such as autism and ADHD in children.” Though the regulator did not provide specific data in its news release, it referenced the Nurses’ Health Study II and the Boston Birth Cohort, which it said “find this association.”
“A causal relationship has not been established,” the agency wrote on Monday, noting that “there are contrary studies in the scientific literature.” Still, the FDA issued a letter to warn physicians nationwide about the potential link between acetaminophen use in pregnancy and adverse neurological outcomes in children.
A hypothetical link between acetaminophen usage during pregnancy and autism has been studied and rejected by researchers before. As recently as 2024, researchers studying a cohort of 2.5 million children born between 1995 and 2019 found no association between the use of the painkiller and autism.
The FDA’s actions on Monday come as Health Secretary Robert F. Kennedy Jr.’s self-imposed deadline nears. In April, Kennedy promised that he would herald the agency’s resources to mount a “massive testing and research effort” to identify the root cause of autism “by September.”
