In an unexpected move, the Food and Drug Administration (F.D.A.) has given its nod to an existing generic drug for autism treatment, a decision that has left many experts bewildered and concerned about the agency’s departure from its usual rigorous review process.
The drug in question, leucovorin, is typically used to counteract the toxic effects of chemotherapy. However, it received a surprising endorsement from President Trump and top U.S. health officials during a White House briefing, where it was presented as a therapy for certain individuals with autism.
This approval dramatically upended the conventional drug review pathway. Usually, a pharmaceutical company conducts extensive studies, often with the F.D.A.’s guidance on study design, before submitting a formal application for approval. In this particular instance, the F.D.A. claims it independently reviewed existing medical research to make the decision to broaden the drug’s use.
“Mr. President, you told us to do what’s medically right — to go bold and not worry about the corporations and the lobbyists,” F.D.A. commissioner Dr. Marty Makary stated during the briefing. “So that’s what we’re here doing today.”
Dr. Makary’s announcement coincided with a presidential briefing on autism, where President Trump repeatedly and controversially suggested a direct link between Tylenol (acetaminophen) and autism, a connection that remains scientifically unproven.
The F.D.A., in contrast, adopted a more measured tone in its communications to doctors, acknowledging that while some evidence hints at an association between Tylenol and autism, this remains an area of scientific contention. Health officials pledged to invest in further studies to explore this potential link. Kenvue, the manufacturer of Tylenol, maintains that its product does not cause autism and is safe when used as directed.
Following the White House announcement regarding prescription leucovorin, there was an immediate scramble for over-the-counter supplements containing folinic acid, a modified form of vitamin B9 (folate) that is the active ingredient in the drug. Online supplement retailer iHerb quickly sold out of its house-brand folinic acid, with its website indicating that new stock wouldn’t be available until late November.
The controversy also cast a spotlight on Dr. Mehmet Oz, the celebrity doctor now heading the Centers for Medicare and Medicaid Services. Dr. Oz, who was present at the White House announcement, had previously been a pitchman for iHerb and held significant shares in the company, reportedly valued between $5 million and $25 million. A spokesperson for the Centers for Medicare and Medicaid Services confirmed that Dr. Oz had divested his iHerb stock and resigned from his company positions earlier in the spring.
Despite the White House event, the health department clarified on X (formerly Twitter) that discussions solely focused on leucovorin and emphasized that the drug should “not be conflated with ANY over-the-counter drugs or supplements.”
During the briefing, Dr. Makary enthusiastically promoted the prescription drug, suggesting it could benefit “hundreds of thousands” of autistic children. However, the F.D.A.’s official notice in the Federal Register detailed a more restricted application. The agency approved leucovorin tablets specifically for “cerebral folate deficiency,” a condition marked by low spinal fluid levels of folate, a B vitamin, which is linked to developmental delays and impaired motor skills in children. Dr. Makary, in an interview with ABC News, estimated that this deficiency affects 20 to 50 percent of children with autism.
Some external medical experts have voiced significant concerns, noting that the F.D.A.’s decision on leucovorin, thought to aid speech and cognitive function in autistic individuals, leaves numerous critical questions unanswered. Dr. Aaron Kesselheim, a Harvard Medical School professor, described the F.D.A.’s swift endorsement as “shocking.” He pointed out that doctors would need a clear method to diagnose cerebral folate deficiency, a process that, without further guidance, might necessitate a costly and risky spinal tap. Furthermore, he highlighted that the F.D.A.’s cited study demonstrated only minor improvements in autism symptoms for individuals with specific spinal fluid folate levels.
“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 F.D.A.’s recommendation as a “science communication disaster.” She argued that the general public would likely misunderstand that the treatment applies only to a subset of patients, and that the ambiguity of the announcement seemed intentional. “Like: ‘We solved it,’” she remarked, suggesting this was the administration’s desired message.
Lynch also noted that the approval process, including the reliance on a small study, falls considerably short of the F.D.A.’s usual standards for reviewing treatments for prevalent conditions like autism. Small studies are typically reserved for extremely rare diseases that are challenging to investigate. “I think this is a dangerous kind of subversion of what F.D.A. approval is supposed to be,” she concluded.
The F.D.A. has requested GSK, the original developer of leucovorin, to update the product’s label. This is a standard procedure that allows generic drug manufacturers to incorporate the new usage information. GSK, which no longer sells the drug, has committed to updating the label. Daniel Aaron, an associate professor of law at the University of Utah specializing in the F.D.A., warned that this decision could set a risky precedent, potentially encouraging other companies to bypass expensive and time-consuming clinical trials before seeking F.D.A. approval. “This approval could very much well come to haunt the F.D.A.,” he cautioned.
Meanwhile, some consumers are not waiting for prescriptions. Folinic acid supplements, which offer a lower dose of the active ingredient than prescription leucovorin, are readily available online without a doctor’s note. This provides a more convenient, albeit less regulated, option for parents looking to purchase the product. Various supplement companies also market other forms of folate, a nutrient naturally found in foods like beans, leafy greens, eggs, beets, and citrus. Folic acid, another form of folate, has been added to many foods for decades to prevent neural tube defects in infants.
Some supplement companies have capitalized on the renewed interest in folate to promote their products. For instance, The Wellness Company, a Florida-based supplement seller with ties to prominent Trump supporters, sent a marketing email advertising a Vitamin B product containing folate. The email stated: “No, we’re not claiming it is going to cure or prevent autism. We simply believe that good nutrition and wise supplementation are keys to a healthier lifestyle.”
Similarly, iHerb, a major online supplement retailer, reported that its California Gold Nutrition brand of folinic acid sold out, although the company attributed some of this increased demand to a September sale. Edward V. Quadros, a research professor at SUNY Downstate Health Sciences University who studies the link between folate and autism, noted that parents of autistic children have historically used folinic acid supplements when access to the prescription drug was limited. However, he expressed hesitation in recommending online folinic acid supplements due to the less stringent manufacturing regulations compared to prescription drugs. Supplement industry trade groups emphasized that their members adhere strictly to rules preventing claims that their products cure, mitigate, or treat diseases. Yet, they highlighted the importance of folate and welcomed the administration’s focus on its health benefits. “Folate is important, and anything that reiterates the importance of folate is, I think, critical to American health,” said Daniel Fabricant, president and CEO of the Natural Products Association. “At the same time, we have restrictions on what we can and can’t say, and we’re going to abide by those.”