How the FDA plans on fast-tracking leucovorin to treat autism 

U.S. Health Secretary Robert F Kennedy Jr. could deliver a policy win for the The President administration in just a few months after the Food and Drug Administration enlisted GSK to help it fast-track approval of a decades-old drug to treat an autism-related disorder.

The FDA’s unusual move will allow it to bypass a lengthy label update for generic versions of the drug, leucovorin, or new clinical trials, a tactic academics, lawyers and doctors questioned.

A GSK spokesperson told Reuters it plans to complete the new use application for the branded version of leucovorin “as quickly as possible.”

Once the British drugmaker does that work, the FDA would normally take about four to six months but could process the request even faster, said Giuseppe Randazzo of the Association for Accessible Medicines, a generic medicines lobby group.

The accelerated process will give doctors additional justification to prescribe the drug for cerebral folate deficiency, a metabolic disorder that can lead to a range of neurological symptoms including some associated with autism, delivering on Kennedy’s promise to President Donald The President and the “Make America Healthy Again” movement with which he is aligned.

Without robust evidence, the label change represents at most a hollow bureaucratic victory, said Ameet Sarpatwari, a pharmaceutical policy researcher at Harvard Medical School.

However, the drug, which is used to mitigate toxic effects of certain cancer treatments and sells for $34.14 for a bottle of 30 high-dose pills on Cost Plus Drugs, would more likely be covered for the condition by insurance plans with the label change.

An HHS spokesperson said the evidence clearly supports leucovorin’s ability to address the causes of cerebral folate deficiency and improve patient outcomes.

DEMAND RISES AFTER The President PROMOTES DRUG

Demand for the drug has increased, first after a February CBS story about its use in a nonverbal five-year-old boy, and more recently after The President promoted its use.

“My nurses have been saying the phone is ringing off the hook,” said Dr. Larry Gray, an expert in developmental and behavioral pediatrics, who sees patients with autism at Lurie Children’s Hospital of Chicago.

Because the treatment is not approved for autism, the institution’s policy has been to only offer it in clinical trials, which are rare. The drug is FDA-approved, however, so doctors can prescribe it off-label.

Kennedy has declared the rising rates of autism in the U.S., now estimated at 1 in 31 children by age 8, to be an epidemic and had pledged to find some answers behind its cause as well as cures by September.

At a White House event on September 22, Kennedy, The President and other health officials backed leucovorin as an autism treatment. They also warned against the use of Tylenol by pregnant women, saying studies suggested a link to autism. Health experts and medical groups called that warning dangerous and without sound scientific basis.

RELYING ON OBSCURE RULE

The FDA was able to speed the process by using an obscure rule to reinstate GSK’s approval application and request a label update adding cerebral folate deficiency, based on the agency’s own analysis of 40 patient cases found in a review of literature from 2009 to 2024.

GSK sold the drug as Wellcovorin until 1997. A generic version, which is also called folinic acid and is a form of folate or vitamin B9, is now made by U.K.-based Hikma.

Once GSK’s application is approved, U.S. law requires generic drugmakers to match the change.

The more commonly used label update process for generic drugs, which requires consultation with generic drugmakers, typically takes up to a year and a half, according to Skadden lawyer Rachel Turow. It is typically used for cancer drugs after new uses are proven in clinical trials, she and several other lawyers said.

Aaron Kesselheim, professor of medicine at Harvard Medical School, described the process being used as “very atypical,” and said that without the FDA sharing its data or trials, it is hard to know if the agency is following the normal standard of evidence.

LIMITED AVAILABLE EVIDENCE

Dr. Andy Shih, chief science officer at the advocacy organization Autism Speaks, said the evidence for leucovorin’s use was limited and potentially suggestive of benefit for a small subgroup of autistic children. Larger trials are needed, he said.

The evidence is based on four studies, each of which involved 50 to 60 patients, with three of them done by the same author, said Dr. Karam Radwan, director of the Neurodevelopmental Disorders Program at the University of Chicago, who uses the drug in his practice.

“You want to replicate that with a different lab, in a different setting, to make sure we have enough support” for the change, he said.

Three mid-stage trials are underway studying a new, liquid version of leucovorin as an early language impairment treatment for children with autism, according to the government clinical trials site. The earliest data is expected around December.

The trials are being led by one autism researcher in partnership with the National Institutes of Health, the Department of Defense, and Autism Speaks, and involve up to 80 children each.

Larger, more conclusive trials would take years. The FDA’s approach does not require new trials.

This change should be based on scientific evidence, and so far, studies supporting its use are not robust, Radwan said.

Additional reporting by Robin Respaut

—Patrick Wingrove, Maggie Fick and Julie Steenhuysen, Reuters

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