FDA approves leucovorin for ultra-rare CFD-FOLR1 subset without trial

The FDA updated the leucovorin label to treat cerebral folate deficiency caused by FOLR1 mutations (CFD-FOLR1), a ultrarare condition linked to autism features, approving the drug based on published case reports and mechanistic rationale rather than a randomized trial. The decision narrows the target population to CFD-FOLR1 after reviewers found the highest-quality data in this subgroup; the move relies on real-world evidence and a plausible mechanism pathway. GSK will stop manufacturing Wellcovorin, but generics exist and importation is allowed; broader autism use remains controversial and calls for more research.