In taking the unusual step of approving an old generic drug as a treatment for autism, the Food and Drug Administration stunned some experts by departing sharply from the agency’s typical standard for reviewing drugs.
The drug, leucovorin, has long been used to treat the toxic effects of chemotherapy, but it was endorsed as a therapy for some people with autism by President Trump and top U.S. health officials during a White House briefing on Monday.
The move flipped the standard process: Typically, a pharmaceutical company carefully studies a drug, often with input from the F.D.A. on the design of rigorous studies, and then files a formal application for approval.
But in this case, the agency said it reviewed medical research and made the approval decision to expand the drug’s use on its own.
“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, said on Monday. “So that’s what we’re here doing today.”
Dr. Makary announced the sudden change during the president’s briefing on autism, which Mr. Trump repeatedly used to directly link Tylenol, the brand-name version of acetaminophen, to the disorder — a connection that is still unproven.
The F.D.A. was more cautious in a letter to doctors, saying evidence suggested a link between Tylenol and autism, though the agency added that the association remained an “area of scientific debate.” The health officials promised to fund more studies to explore a potential connection. Kenvue, the maker of Tylenol, has said the drug does not cause autism and is safe to use as directed.
While the White House announcement concerned only the prescription drug leucovorin, there were early signs that the federal government’s endorsement had already spurred a run on over-the-counter supplements containing the active ingredient in the drug, folinic acid, which is a modified version of vitamin B9, also known as folate.
A prominent online supplement seller, iHerb, said that it had sold out of its in-house brand of folinic acid on Tuesday. The company’s website said the product would not be back in stock until late November.
The announcement put a spotlight on the company for its now-severed ties with Dr. Mehmet Oz, the celebrity doctor who heads the Centers for Medicare and Medicaid Services. Dr. Oz, who joined Mr. Trump and Dr. Makary for the announcement on Monday, previously acted as a pitchman for iHerb and had holdings in the company that were valued at an unspecified figure in the range of $5 million to $25 million, according to his disclosure forms.
In a disclosure form signed in June by Dr. Oz, he reported that he had sold his stock in iHerb. He also resigned from positions with the company earlier this spring, a spokesman for the Centers for Medicare and Medicaid Services said.
The health department said in a post on X that Mr. Trump and health officials had discussed only leucovorin on Monday, and that the drug was “not to be conflated with ANY over-the-counter drugs or supplements.”
At the briefing on Monday, Dr. Makary promoted the prescription drug as likely to help “hundreds of thousands” of children with autism. Yet the agency’s notice in the Federal Register indicated a narrower application.
The F.D.A. approved tablets of leucovorin specifically to treat “cerebral folate deficiency,” a condition characterized by low levels of folate, a B vitamin, in spinal fluid that is associated with delays in a child’s development and poor motor skills. Dr. Makary said in an interview with ABC News that about 20 to 50 percent of children with autism had the deficiency.
Some outside experts said that the agency’s decision on leucovorin, which is believed to improve speech and cognitive abilities in people with autism, left many questions unanswered.
Dr. Aaron Kesselheim, a professor of medicine at Harvard Medical School, called the F.D.A.’s hasty endorsement of leucovorin “shocking.”
Before prescribing the tablets, doctors would first need to determine whether a patient suffered from the deficiency, Dr. Kesselheim said. How they would arrive at that diagnosis short of a risky, expensive spinal tap was not clear, he said.
The F.D.A.’s action also failed to clarify the appropriate dose of leucovorin for children and adults, which is typically determined by each drugmaker from clinical studies. Dr. Kesselheim also noted that the study cited by the F.D.A. showed only small improvements in autism symptoms among people with certain folate levels in their spinal fluid.
“This puts the cart about three miles in front of the horse,” Dr. Kesselheim said. “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, said the agency’s recommendation seemed like a “science communication disaster.” Few people would be likely to realize that a treatment touted as a salve for autism only applied to a subset of patients, she said, adding that the vagueness of the announcement seemed intentional.
“Like: ‘We solved it,’” she said. “That’s exactly what this administration wanted.”
The approval itself, including a description of a small study, also falls far below the agency’s standard for reviewing a treatment for a condition as common as autism, she said. Small studies are not unheard-of, but are typically done in the case of an extremely rare disease that is difficult to examine.
“I think this is a dangerous kind of subversion of what F.D.A. approval is supposed to be,” she said.
The F.D.A. asked GSK, the original company that applied for approval of leucovorin, to update the label on the product, which the company sold during the 1980s and 1990s. It is a procedural step that will enable several companies that make generic versions to adopt the label’s language. GSK said in a statement that it no longer sells the drug, but will update the label.
Daniel Aaron, an associate professor of law at the University of Utah who studies the F.D.A., said the agency’s decision on leucovorin could set a precedent for other companies that want to skip costly, careful and yearslong clinical trials before asking the agency for an approval.
“This approval could very much well come to haunt the F.D.A.,” he said.
Some customers on Tuesday appeared not to be waiting for a prescription. Folinic acid supplements, which deliver a lower dose of the ingredient than leucovorin, can be purchased online without a prescription, creating a more convenient, and also more lightly regulated, avenue for parents to buy the product.
Supplement companies make and sell other forms of folate, too, which is naturally found in beans, leafy greens, eggs, beets and citrus. Those include folic acid, which for decades has also been added to certain foods to reduce the risk of babies being born with neural tube defects.
Some supplement companies seized on the newfound attention to folate to promote their own products.
In a marketing email on Tuesday morning, The Wellness Company, a Florida supplement seller that has ties to prominent supporters of Mr. Trump’s, advertised a Vitamin B product that contains folate.
“No, we’re not claiming it is going to cure or prevent autism,” the email said. “We simply believe that good nutrition and wise supplementation are keys to a healthier lifestyle.”
And iHerb, the online supplement seller, sold out of its own California Gold Nutrition brand of folinic acid, though the company said that purchases of the product had already been trending higher because of a September sale.
Parents of autistic children have turned to folinic acid supplements as a way of overcoming difficulties accessing the drug in the past, said Edward V. Quadros, a research professor at SUNY Downstate Health Sciences University who has studied the relationship between folate and autism.
He said he was reluctant to suggest online folinic acid supplements himself because the manufacturing of those products is not as stringently regulated as the manufacturing of drugs.
Supplement industry trade groups said that their member companies were careful to abide by rules restricting them from saying that their products cure, mitigate or treat disease. But they noted that not everyone has access to a doctor who can prescribe the drug form of folinic acid, and they cheered the administration’s emphasis on the health benefits of folate.
“Folate is important, and anything that reiterates the importance of folate is, I think, critical to American health,” said Daniel Fabricant, the president and chief executive of the Natural Products Association, a leading trade association for the dietary supplement industry. “At the same time, we have restrictions on what we can and can’t say, and we’re going to abide by those.”
Reed Abelson contributed reporting.
Christina Jewett covers the Food and Drug Administration, which means keeping a close eye on drugs, medical devices, food safety and tobacco policy.
Benjamin Mueller reports on health and medicine. He was previously a U.K. correspondent in London and a police reporter in New York.
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