FDA Withdraws GSK Wellcovorin Approval After Autism Treatment Controversy

The FDA formalized the end of the Wellcovorin era on April 9 after GlaxoSmithKline notified the agency in writing that the drug was no longer marketed and requested its New Drug Application be withdrawn. The Federal Register notice that followed is administrative rather than safety-driven, but it closes a politically charged regulatory saga that exposed a significant gap between public claims and clinical evidence.

The controversy traces to a September 2025 press conference at which FDA Commissioner Dr. Marty Makary, appearing alongside President Trump, cited a study of 48 autistic patients and told the public that leucovorin, the active ingredient in Wellcovorin, could benefit what he described as "hundreds of thousands of kids" with autism. Trump used the same occasion to make unsubstantiated claims about Tylenol and autism. The public expectations raised by those statements set up a collision course with the FDA's own evidence review.

When that review concluded on March 10, regulators found they could only support approval for cerebral folate transport deficiency caused by pathogenic variants in the folate receptor 1 gene, an ultra-rare neurological condition known as CFD-FOLR1 and estimated to occur in roughly 1 in a million people. The supporting case data was narrow: 46 patients who had received leucovorin appeared in past reports, ranging in age from 2 months to 33 years. Of the 27 who took oral leucovorin exclusively, 24, or 89 percent, showed clinical improvements including reductions in seizure severity and gains in motor function. That data supported a first-ever treatment approval for CFD-FOLR1. It did not support a broad autism indication.

Independent researchers made the evidentiary problem explicit well before the March decision. Two scientists writing in the New England Journal of Medicine in January 2026 stated that "there is no substantive evidence that cerebral folate deficiency plays a role in the pathogenesis of autism," describing claims about folate receptor antibodies as "inconclusive." All studies of leucovorin in autistic patients have been small, and at least one was recently retracted.

GSK originally sold Wellcovorin from 1983 to 1997 before withdrawing from the market after generics arrived. The company confirmed it had no plans to manufacture the product following the March approval, making the NDA withdrawal a predictable outcome. The practical consequence falls on a small but medically vulnerable group: patients diagnosed with CFD-FOLR1 who relied on branded Wellcovorin will need clinicians to identify compounding options, generic alternatives, or other suppliers. Because generic leucovorin manufacturers mirror the brand originator's approved label, that label question now filters through the generics market.

The broader reckoning concerns how regulatory communication failed the standard it is meant to uphold. The FDA entered the Wellcovorin review considering whether a wider autism indication might be warranted, driven partly by political momentum, and found the evidence did not support it. Clinicians and scientists who had refused to prescribe the drug off-label for autism, citing unproven benefits against real risks including anaphylaxis and allergic reactions, were ultimately vindicated by the agency's own findings. What the Wellcovorin episode leaves unresolved is how the FDA and HHS plan to address the transparency problem created when senior officials promote indications that the agency's evidence standards cannot subsequently support.