FDA Approves First Treatment for Patients with Cerebral Folate Transport Deficiency

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency?utm_medium=email&utm_source=govdelivery The U.S. Food and Drug Administration today approved expanded use of Wellcovorin (leucovorin calcium) 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). This action reflects the agency’s commitment to accelerating cures and expanding treatment options including for patients with serious and unmet needs. Leucovorin is the first treatment for the rare genetic condition of cerebral folate deficiency. 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. Cerebral folate deficiency is a neurological condition that affects folate (a vitamin essential for brain health) transport into the brain. People with CFD-FOLR1 often have severe developmental delays, movement disorders, seizures, and other serious neurological complications. "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,” said FDA Commissioner Marty Makary, M.D., M.P.H. “This action may benefit some individuals with FOLR1- related cerebral folate transport deficiency who have developmental delays with autistic features.” The FDA collaborated with GSK, the New Drug Application holder of Wellcovorin, 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. "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, M.D., Ph.D., 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.” Possible side effects associated with leucovorin include pruritus (itching), rash (irritated, inflamed skin), urticaria (more commonly known as hives), dyspnea, rigors (sudden feeling of cold with shivering), and impaired thermoregulation (spontaneous changes in body temperature). Anaphylaxis (a severe, rapid, and potentially fatal allergic reaction) is a serious side effect requiring immediate medical attention. Today’s approval addresses a critical need for individuals with CFD-FOLR1 and builds on the FDA's commitment to advancing the health of all Americans, including those affected by rare genetic conditions. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2026/018342Orig1s015ltr.pdf?utm_medium=email&utm_source=govdelivery