Wellcovorin’s Second Chance for Autism Symptoms
The FDA took the rare step of reopening the approval process for GSK’s Wellcovorin, aiming to return the therapy to the market more than two decades after it was withdrawn, this time as a possible option for easing symptoms of autism.
The agency has begun evaluating Wellcovorin – leucovorin’s branded form – for the treatment of cerebral folate deficiency (CFD). This disorder is marked by low folate levels in the brain even when blood concentrations appear normal. According to the FDA, CFD has been tied to developmental issues with autism-like traits, as well as seizures and motor impairments.
To support its position, the FDA said Monday that it reviewed a broad set of research conducted between 2009 and 2024, incorporating both individual patient data and mechanistic evidence. The findings, according to the agency, indicate that leucovorin can be beneficial for patients with CFD. However, the Department of Health and Human Services cautioned in its own announcement that leucovorin should not be considered a cure for autism spectrum disorder (ASD). Instead, the therapy may only help a subset of children, particularly in easing speech-related challenges.
A Look Back at Wellcovorin
Wellcovorin first entered the U.S. market in 1983, when it was cleared as a rescue therapy to counteract the toxicities of methotrexate and overdoses of folic acid antagonists. The medicine was later withdrawn in 1997, as GSK discontinued sales. Even so, its active component, leucovorin, remains available in the country as a generic.
FDA’s Center for Drug Evaluation and Research director George Tidmarsh said the agency is collaborating with GSK to expand Wellcovorin’s approved uses. In line with this, the company has signaled its plan to submit a supplemental application seeking approval of the drug for CFD.
Broader FDA Actions on Neurodevelopmental Conditions
In a separate action that same day, the FDA also moved to update the labeling of Tylenol and other acetaminophen-based products. The revision is intended to reflect growing evidence that prenatal exposure may be associated with a higher risk of neurodevelopmental conditions such as autism and ADHD in children.
The FDA emphasized that no causal link has been proven, pointing out that other studies in the scientific literature contradict the suggested connection. Nevertheless, the agency has circulated a nationwide advisory letter to clinicians about the possible association between acetaminophen usage during pregnancy and neurodevelopmental risks in children.
The idea that acetaminophen could contribute to autism has been raised and dismissed before. In fact, a 2024 analysis of 2.5 million children born from 1995 to 2019 reported no correlation between prenatal use of the drug and autism diagnoses.
Context of a Larger Push
The FDA’s announcements also coincide with a pledge made earlier this year by Health Secretary Robert F. Kennedy Jr., who in April vowed to utilize the agency’s resources to conduct large-scale testing and research aimed at uncovering the root causes of autism, with a self-set deadline of September.
As the FDA proceeds with this unusual regulatory reopening, many questions remain. The evidence supporting leucovorin’s benefit in autism is largely drawn from small studies, case reports, and mechanistic connections — not from large, controlled trials involving broad ASD populations. Experts caution that while the FDA’s move is bold, it carries risks: widespread use before definitive proof of efficacy or safety could lead to false hope or misuse. Some in the autism research community have already voiced caution, urging that further controlled trials be prioritized before the therapy becomes standard care.
Moreover, if the new indication for Wellcovorin is approved, the FDA and GSK will have to work closely with payers, clinicians, and advocacy groups to manage expectations, access, and monitoring of outcomes in real-world settings. The reopening of Wellcovorin’s approval is a signal that the FDA sees potential in repurposing older drugs for neurodevelopmental needs — but ultimately the outcome will depend on rigorous data, balanced messaging, and careful clinical oversight.