FDA’s Move to Update GSK’s Leucovorin for Autism Raises Questions on Dose, Supply, and Data

The FDA is taking the unusual step of seeking to relabel GSK's old drug, leucovorin (formerly Wellcovorin), as a treatment for symptoms of autism connected to cerebral folate deficiency1 3 4 5 6.

Leucovorin was marketed by GSK from 1983 until 1997, after which it was withdrawn and became available in generic forms in the U.S.; GSK no longer manufactures the original brand version1.

The move comes after FDA review of published literature (2009–2024) indicated potential benefit for speech and autism-related deficits in patients with cerebral folate deficiency1.

GSK has agreed to submit a supplemental new drug application at the FDA’s request, incorporating case reports of genetically confirmed cerebral folate deficiency, but its announcement made no direct reference to autism1 6.

Critics and experts have raised questions about optimal dosing for autism, the reliable long-term supply of the repurposed drug (given the original is off the market), and the sufficiency of clinical data to support the expanded use1 2.

A change in official drug labeling could increase insurance coverage for this use, driving increased demand and clinical attention1.

No new large, randomized clinical trials are cited; instead, changes are based on case reports and literature review, raising concerns about the adequacy of the evidence base1.

The FDA's action is part of a broader set of announcements on neurodevelopmental safety and treatments, including an update to acetaminophen (Tylenol) labeling for pregnant women1 2.