Dive Brief:

• The Food and Drug Adminstration has cleared an old GSK drug called Wellcovorin for an exceedingly rare neurological syndrome, rather for than autism, reflecting a significant change from what one of the agency’s top officials had set out to do months ago.
• Wellcovorin, sold generically as leucovorin, is now approved to treat cerebral folate deficiency in adults and children confirmed to have a certain kind of genetic variant. It’s a condition that, by some estimates, has been documented in fewer than 50 people. The FDA’s decision “may benefit some individuals” with this specific form of the disease who have “developmental delays with autistic features,” Commissioner Martin Makary said in a release.
• Standing alongside President Donald Trump, Makary in September said the agency was moving toward approving Wellcovorin to make it available to children with autism. “Hundreds of thousands of kids, in my opinion, will benefit,” he said at the time.

Dive Insight:

The FDA’s actions have been unusual from the start of this leucovorin saga. The decades-old drug is often used to help cancer patients fight side effects of chemotherapy and other treatments that block the beneficial actions of folic acid. GSK developed Wellcovorin and sold it from 1983 to 1997. After generic forms hit the market, the British pharmaceutical giant stopped selling the medicine and asked the FDA to withdraw the approval for Wellcovorin, which it did.

Then last year, the FDA went to GSK and asked it to submit a new application for cerebral folate deficiency based on data from case reports. Even though GSK had no intention of manufacturing or marketing the medicine again, the agency needed the original developer to apply for the new label.

The process bypassed the usual rules of drug development, where approvals are based on clinical studies overseen by the FDA — not on past data gathered through literature. It also stood in stark contrast to the agency’s handling of other rare disease drugs and vaccines, where officials in Trump’s second term often appear to be seeking more evidence to approve new products.

It was a link to autism that caught the administration’s attention. Some researchers have drawn a connection from cerebral folate transport deficiency to autistic patients who have a blockage that affects the body’s ability to carry folate into the brain. The Health and Human Services Department in September said cerebral folate transport deficiency was “associated” with autism.

During the September press conference — in which Trump also made unfounded claims about the potential for Tylenol to cause autism — Makary said he had a duty to let doctors and the public know about leucovorin. He referenced a study of 48 people with autism that suggested the medication could trigger improvements in speech.

But studies of the drug in autistic patients have all been small. And one was recently retracted. Agency officials went into the Wellcovorin process considering a broader autism approval but in the end could only find evidence to clear it for cerebral folate deficiency, The Washington Post reported.

Instead of hailing the latest approval as a victory for autistic patients, FDA officials highlighted the first approval of a drug for cerebral folate deficiency. It “demonstrates the FDA’s commitment to rapidly identifying effective treatments for ultra rare diseases while maintaining the same evidentiary standards for approval,” Tracy Beth Høeg, the acting head of the FDA’s main drug review division, said in the agency’s release.

Despite a lack of evidence, Trump and Makary’s press conference in September sent many parents of autistic children scrambling to get leucovorin, which doctors could prescribe “off-label” before the official approval. One study in The Lancet found that prescriptions for the drug jumped 71% in the following months.

Many doctors also refused to give the medicine to their autistic patients, fearing that the risks might outweigh as-yet unproven benefits. Leucovorin’s potential side effects include allergic symptoms such as rash and hives, spontaneous changes in body temperature and anaphylaxis, the FDA said Tuesday.