The U.S. Food and Drug Administration (FDA) has started the process to approve leucovorin calcium tablets as a treatment for patients with cerebral folate deficiency (CFD), a neurological disorder that affects the delivery of folate, a critical vitamin for brain function, into the central nervous system. Those with CFD typically exhibit developmental delays, autistic behavior with impaired social interaction and repetitive behavior, and seizures and movement disorders.
As part of the process, the FDA conducted a thorough analysis of the published literature from 2009 until 2024. This analysis involved case reports with individual patient data, in addition to mechanistic data. Based on this body of evidence, the agency determined that leucovorin calcium demonstrates therapeutic benefit for individuals living with cerebral folate deficiency.
“We have witnessed a tragic four-fold increase in autism over two decades,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Children are suffering and deserve access to potential treatments that have shown promise. We are using gold standard science and common sense to deliver for the American people.”
The agency has also confirmed that it is working with GSK, the developer of Wellcovorin (leucovorin calcium), to ensure that scientific information necessary for safe and effective use is included in the labeling for both adult and pediatric patients with CFD. GSK, as the holder of the New Drug Application for this therapy, has indicated its willingness to collaborate with regulators on this relabeling initiative.
“The FDA is collaborating with GSK to broaden the existing Wellcovorin label,” said George Tidmarsh, M.D., Ph.D., Director of the FDA’s Center for Drug Evaluation and Research. “This effort reflects the FDA’s commitment to identify opportunities to repurpose drugs to treat chronic diseases. The FDA remains committed to finding and treating the root causes of autism.”
While CFD has been observed in wider patient groups who exhibit neuropsychiatric symptoms, including autistic traits and the presence of folate receptor alpha autoantibodies, the agency noted that existing data on leucovorin use in these populations remains limited. Additional studies will be required to establish its safety and efficacy beyond the current scope.
