The Food and Drug Administration has taken an extraordinary step, approving an older generic drug as a treatment for autism. This move has shocked many experts, as it deviates significantly from the agency’s established standards for drug review.
The drug, leucovorin, traditionally used to counteract the toxic effects of chemotherapy, was suddenly endorsed as an autism therapy by President Trump and prominent U.S. health officials during a White House briefing on Monday.
This decision inverted the usual approval pipeline. Typically, a pharmaceutical company invests years in carefully studying a drug, often collaborating with the FDA on study design, before submitting a formal application for approval.
However, in this instance, the agency declared it had independently reviewed existing medical research and decided, on its own, to broaden the drug’s approved uses.
“Mr. President, you told us to do what’s medically right — to go bold and not worry about the corporations and the lobbyists,” Dr. Marty Makary, the F.D.A. commissioner, stated on Monday. “So that’s what we’re here doing today.”
Dr. Makary’s sudden announcement came during the president’s briefing on autism, where Mr. Trump repeatedly attempted to link Tylenol (acetaminophen) to the disorder, a connection that remains scientifically unproven.
The F.D.A. adopted a more cautious tone in a letter to doctors, acknowledging that evidence *suggested* a link between Tylenol and autism, but emphasized that this association is still an “area of scientific debate.” Health officials pledged further studies to investigate this potential connection. Kenvue, the manufacturer of Tylenol, maintains that their product does not cause autism and is safe when used as directed.
Outside experts expressed considerable apprehension, noting that the agency’s decision left many critical questions unanswered.
Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, described the FDA’s swift endorsement of leucovorin as “shocking.”
At the White House briefing, Dr. Makary enthusiastically presented the drug as a potential aid for “hundreds of thousands” of children with autism. Yet, the agency’s own notice in the Federal Register specified a much narrower application for the drug.
The FDA’s approval for leucovorin tablets was specifically limited to treating “cerebral folate deficiency,” a condition marked by low levels of the B vitamin folate in spinal fluid, which can be linked to developmental delays and impaired motor skills in children.
According to Dr. Kesselheim, doctors would first need to diagnose a patient with this specific deficiency before prescribing the tablets. He questioned how such a diagnosis could be reliably made without a potentially risky and expensive spinal tap.
Furthermore, the FDA’s action did not provide clear guidance on the appropriate dosage of leucovorin for pediatric and adult patients, information usually established through extensive clinical trials conducted by drugmakers. Dr. Kesselheim also pointed out that the study cited by the FDA indicated only modest improvements in autism symptoms among individuals with specific folate levels in their spinal fluid.
“This puts the cart about three miles in front of the horse,” Dr. Kesselheim asserted. “The reason we have F.D.A. is to try to help patients distinguish between things that do and don’t work.”
Holly Fernandez Lynch, an associate professor of law at the University of Pennsylvania, characterized the agency’s recommendation as a “science communication disaster.” She predicted that few would grasp that a treatment touted as a solution for autism only applied to a small subset of patients, suggesting the announcement’s ambiguity might have been deliberate.
“Like: ‘We solved it,’” she remarked. “That’s exactly what this administration wanted.”
The approval itself, based on a limited study, falls significantly short of the agency’s typical standards for evaluating treatments for widespread conditions like autism, she noted. While small studies can be acceptable for extremely rare diseases that are hard to research, this situation is different.
“I think this is a dangerous kind of subversion of what F.D.A. approval is supposed to be,” she warned.
The FDA has requested GSK, the original applicant for leucovorin’s approval, to update the product’s label. GSK, which sold the drug in the 1980s and 1990s, will comply, a procedural step enabling generic manufacturers to adopt the new labeling. However, GSK confirmed in a statement that it no longer sells the drug.
Daniel Aaron, an associate professor of law at the University of Utah specializing in FDA studies, cautioned that this decision regarding leucovorin could establish a risky precedent. It might encourage other companies to circumvent the costly, extensive, and years-long clinical trials typically required for drug approval.
“This approval could very much well come to haunt the F.D.A.,” he concluded.