FDA

FDA approves Wellcovorin (leucovorin) as first treatment for cerebral folate deficiency

March 11, 2026

On March 10, 2026, FDA approved Wellcovorin (leucovorin) tablets as the first treatment for adult and pediatric patients with cerebral folate transport deficiency and a confirmed folate receptor 1 gene variant (FOLR1-CFTD). The approval provides clinicians with the first evidence‑based pharmacologic option for a population historically limited to supportive care. Clinically, leucovorin addresses impaired folate transport into the central nervous system—an underlying driver of developmental delay and autistic features in patients with FOLR1-CFTD.

Wellcovorin was already approved in adults to reduce toxicity from methotrexate, folic acid antagonists, or dihydrofolate reductase inhibitors. The product was marketed by GlaxoSmithKline (GSK) from 1983 to 1997. In September 2025, the company announced plans to submit a supplemental new drug application at the FDA’s request to add an indication for treating FOLR1-CFRD.

Efficacy

Approval was based on a systematic review of published case reports and mechanistic data rather than traditional randomized trials. Patients (N=46) with FOLR1-CFTD who received leucovorin treatment via various routes were identified in case reports and reviews published between 2009-2024. Of the 46 patients, a total of 27 (59%) received leucovorin only via the oral route. These patients ranged in age from 2 months to 33 years old. Dosing information was available for 25 patients. The starting oral dose ranged from 0.5 to 3 mg/kg/day, and was 2 mg/kg/day in 14 of the 25 patients. The maximum dose was ≤6 mg/kg/day (reported range: 1.7 to 8.5 mg/kg/day) in 17 of the 25 patients. Information on duration of leucovorin use was limited.

Clinical improvements in various neurological symptoms were reported following oral leucovorin treatment for 24 of the 27 patients (e.g., reduction in severity or number of seizures; improvements in motor function, communication, and/or behavior). The remaining 3 patients showed either no change or no progression of symptoms; both the observed clinical improvements and the lack of disease progression were unexpected when compared to the progressive natural history of FOLR1-CFTD patients.

Safety

Safety data for treating FOLR1‑CFTD with oral leucovorin remain limited, as the available evidence is based on published case reports.

Adverse events reported with post-approval use of leucovorin include pruritus, rash, urticaria, dyspnea, rigors, and impaired thermoregulation. Because these events are reported voluntarily from an uncertain population size, their frequency and any causal link to the drug cannot be reliably determined.

Hypersensitivity reactions, including anaphylactic reactions, have been reported following leucovorin administration, thus Wellcovorin is contraindicated in patients with a history of hypersensitivity reaction to leucovorin (folinic acid), levoleucovorin, folic acid, or any component of Wellcovorin.

Recommended dose

Dosing for treatment of FOLR1‑CFTD is weight-based:

• Weight <40 kg: start 1-2 mg/kg/day orally once daily or divided up to 6 times per day; adjust to max daily dose of 8.5 mg/kg/day
• Weight ≥40 kg: start 1-2 mg/kg/day orally once daily or divided up to 6 times per day; adjust to max daily dose of 330 mg/day

Single doses of ≤25 mg are preferred; max: 75 mg/dose.

Sources:

FDA. (2026, March 10). FDA Approves First Treatment for Patients with Cerebral Folate Transport Deficiency. [Press release]. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-patients-cerebral-folate-transport-deficiency Accessed March 10, 2026.

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

Wellcovorin (leucovorin). [Package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/018342s015lbl.pdf Revised March 2026. Accessed March 10, 2026.