The Food and Drug Administration approved a generic version of the drug leucovorin on Tuesday for children and adults with a rare genetic condition that limits folate delivery to the brain, affecting fewer than 1 in a million people in the United States, according to FDA officials. The approval also came with a shift away from the drug’s earlier high-profile promotion for autism, including statements from President Donald Trump and other administration officials.
In September, Trump and FDA commissioner Marty Makary announced at a White House news conference that leucovorin was under review, saying it could help people with autism. Makary said then, “It might be 20, 40, 50% of kids with autism,” referring to those who have a form of the vitamin-related brain deficiency. On Tuesday, senior FDA officials said the agency’s review had been narrowed to focus on the strongest evidence and that the evidence supported leucovorin’s use only for patients with the rare mutation that affects folate levels in the brain.
FDA officials also said one study used to support leucovorin for autism was retracted earlier this year. Autism researchers reiterated that the drug has not been shown safe or effective for the vast majority of people with the brain disorder. Dr. Alycia Halladay of the Autism Science Foundation said, “There is no evidence to say that leucovorin will help most people with autism, and there’s certainly no evidence to say it’s safe,” in an interview.
Halladay said there is also no established figure for how many people with autism have the folate-related brain disorder. She noted that some doctors diagnose the condition using a specialty laboratory test that isn’t FDA-approved, underscoring the uncertainty around how many patients are being identified for targeted treatment.
The new FDA message landed after months of shifting expectations for families that received prescriptions for autism-related use of leucovorin. David Mandell, an autism expert at the University of Pennsylvania, said off-label prescribing rose after the September announcement, and warned that families are now dealing with changing medical guidance. He said, “We’ve seen huge increases in leucovorin prescriptions for autism because of the initial premature and ill-informed announcement that it can treat autism symptoms.” Mandell added, “Now families are experiencing whiplash about what constitutes best practice for their children.”
Mandell pointed to a paper published in The Lancet last week that found leucovorin prescriptions for children aged 5 to 17 were 71% higher than normal in the three months following Trump’s late September news conference. The FDA’s revised stance also coincided with reports from some families that they have had trouble filling prescriptions in recent weeks, as clinicians and pharmacists navigate whether use aligns with the narrower evidence focus.
FDA officials told reporters that the agency is allowing imports of leucovorin by foreign drugmakers to boost supply, according to the report. The drug’s original manufacturer, GSK, does not plan to relaunch its version of leucovorin, the report said.
Researchers and medical groups have long urged caution. Halladay warned parents against seeking the drug and pointed to reports of side effects including irritability, aggression and hyperactivity when used in people with autism. She said, “If parents are insistent on trying this they should know that it may cause harm and it may do no good.”
The renewed attention also followed a broader dispute inside the administration over what causes autism. The White House event touting the drug came after promises from Health Secretary Robert F. Kennedy Jr. to determine the cause of autism by September, and FDA review was initially prompted after Trump officials spoke with an Arizona-based neurologist who prescribes leucovorin for autism patients and runs an online education business focused on the experimental treatment.
The theory behind the autism-linked use is that some people with autism have antibodies that block folate from entering the brain. But Halladay and other groups said non-autistic relatives of people with the disorder often have the same antibodies, suggesting they are not a factor in the condition. The AP report also noted that while there is no single cause behind autism, most researchers say genetics and environmental factors play a role, and that professional medical societies have said it is far from clear whether leucovorin helps people with autism.