FDA Approves Leucovorin Calcium (Wellcovorin) Tablets as First Cerebral Folate Deficiency Treatment

The US Food and Drug Administration (FDA) has approved GSK’s leucovorin calcium (Wellcovorin) tablets for the treatment of cerebral folate deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (CFD-FOLR1), making it the first treatment for the rare genetic condition of cerebral folate deficiency.

As described in a March 10, 2026, release from the Agency, the approval was based on a systematic review of the published literature on the topic, including published case reports with patient-level information, as well as mechanistic data.

"Today's approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today,” FDA Commissioner Marty Makary, MD, MPH, said in a statement. “This action may benefit some individuals with FOLR1- related cerebral folate transport deficiency who have developmental delays with autistic features.”

In the US, leucovorin is indicated to diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosages of folic acid antagonists. GSK marketed leucovorin under the brand name Wellcovorin from 1983 to 1997, and it is now available in the US as a generic drug.

The FDA collaborated with GSK on a process to update the labeling to include the essential scientific information needed for the safe and effective use of the drug for adults and pediatric patients with CFD-FOLR1, a neurological condition that affects folate transport into the brain.

GSK announced the submission of a supplemental New Drug Application (sNDA) for leucovorin to update the label to include an indication for the treatment of CFD on September 22, 2025. The FDA requested GSK take this action as part of the Agency’s initiative to investigate opportunities to repurpose older medications for the treatment of chronic diseases.

As described by the FDA, possible side effects associated with leucovorin include pruritus, rash, urticaria, dyspnea, rigors, and impaired thermoregulation.

"The approval of leucovorin for FOLR1-related cerebral folate transport deficiency (CFD- FOLR1) demonstrates the FDA’s commitment to rapidly identifying effective treatments for ultra rare diseases while maintaining the same evidentiary standards for approval,” said Tracy Beth Hoeg, MD, PhD, Acting Director of the FDA’s Center for Drug Evaluation and Research. “It also provides a good example of how observational or ‘real world’ evidence can lead to an FDA approval when the product is shown to provide clear clinical benefit compared with what is seen with the natural history of the disease.”

References

1. US Food and Drug Administration. FDA Approves First Treatment for Patients with Cerebral Folate Transport Deficiency. March 10, 2026. Accessed March 10, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency

2. GSK. GSK to submit label update for Wellcovorin (leucovorin) at US FDA’s request. September 22, 2025. Accessed March 10, 2026. https://www.gsk.com/en-gb/media/press-releases/gsk-to-submit-label-update-for-wellcovorin-leucovorin-at-us-fda-s-request/