The Food and Drug Administration recently made an unprecedented move, approving an existing generic drug for autism treatment, a decision that has significantly deviated from its usual stringent drug review protocols and surprised many experts.
This drug, leucovorin, traditionally used to counteract chemotherapy’s toxic effects, received an unexpected endorsement as an autism therapy from President Trump and high-ranking U.S. health officials during a White House press conference on Monday.
This decision completely inverted the conventional drug approval pipeline. Normally, a pharmaceutical company meticulously researches a drug, often collaborating with the FDA on designing robust studies, before submitting a formal application for its approval.
In this instance, however, the agency declared it had independently reviewed existing medical research and decided to broaden the drug’s approved uses on its own initiative.
“Mr. President, you instructed us to prioritize medical best practices — to be audacious and disregard corporate or lobbying pressures,” announced Dr. Marty Makary, the FDA commissioner, on Monday. “That’s precisely what we are accomplishing here today.”
Dr. Makary’s unexpected announcement came during the president’s autism briefing, an event that President Trump controversially used to repeatedly assert a direct link between Tylenol (acetaminophen) and autism, despite this connection remaining scientifically unproven.
The FDA adopted a more measured tone in a communication to medical professionals, acknowledging that some evidence suggested a link between Tylenol and autism, but clarifying that this association is still an “area of scientific debate.” Health officials committed to funding further research into this potential connection. Kenvue, the manufacturer of Tylenol, maintains that their product does not cause autism and is safe when used as prescribed.
Outside experts voiced concerns, stating that the agency’s decision left a multitude of critical questions unaddressed.
Dr. Aaron Kesselheim, a Harvard Medical School professor, characterized the FDA’s rapid endorsement of leucovorin as “shocking.”
During the briefing, Dr. Makary enthusiastically presented the drug as a potential benefit for “hundreds of thousands” of children with autism. However, the agency’s formal publication in the Federal Register outlined a much more restricted application.
Specifically, the FDA approved leucovorin tablets for treating “cerebral folate deficiency,” a condition marked by insufficient levels of folate (a B vitamin) in spinal fluid, which can lead to developmental delays and impaired motor skills in children.
Dr. Kesselheim pointed out that for doctors to prescribe these tablets, they would first need to diagnose a patient with this deficiency. He noted that the method for achieving such a diagnosis, without resorting to a hazardous and costly spinal tap, remained unclear.
Furthermore, the FDA’s action did not specify the correct dosage of leucovorin for pediatric and adult patients, which drug manufacturers usually establish through clinical trials. Dr. Kesselheim also highlighted that the research referenced by the FDA demonstrated only minor improvements in autism symptoms among individuals with specific folate levels in their spinal fluid.
“This situation is akin to putting the cart miles ahead of the horse,” stated Dr. Kesselheim. “The fundamental purpose of the FDA is to assist patients in discerning effective treatments from ineffective ones.”
Holly Fernandez Lynch, an associate law professor at the University of Pennsylvania, commented that the agency’s recommendation appeared to be a “science communication disaster.” She suggested that very few people would grasp that the publicized autism treatment was only relevant to a specific subset of patients, implying the announcement’s ambiguity was deliberate.
“It was like saying: ‘We’ve solved it,'” she explained. “That’s precisely the message this administration aimed to convey.”
She further argued that the approval, even with its brief mention of a small study, significantly undershoots the agency’s usual standards for evaluating treatments, especially for a prevalent condition like autism. While small studies are sometimes acceptable, they are usually reserved for exceptionally rare diseases that are challenging to research thoroughly.
“I believe this represents a perilous undermining of the very essence of FDA approval,” she concluded.
The FDA instructed GSK, the pharmaceutical company that originally sought approval for leucovorin, to revise the drug’s label. GSK, which marketed the product in the 1980s and 1990s, no longer sells it but confirmed it would comply with the label update. This procedural update will allow other manufacturers of generic versions to use the new labeling information.
Daniel Aaron, an associate professor of law at the University of Utah specializing in FDA studies, warned that the agency’s leucovorin decision could establish a concerning precedent. It might encourage other companies to bypass expensive, rigorous, and lengthy clinical trials before seeking FDA approval.
“This approval might very well come back to trouble the FDA,” he predicted.