FDA approves leucovorin for cerebral folate deficiency but not autism

The Food and Drug Administration on Tuesday approved a decades-old prescription vitamin called leucovorin as the first treatment for a rare genetic disorder in some adults and children.

The move comes months after the Trump administration promoted leucovorin as a potential treatment for a broad group of patients with autism spectrum disorder symptoms. The claim raised skepticism among some in the medical and research community, but fueled excitement among families, increasing drug prescriptions in the US.

An FDA official told reporters Monday that “we don’t have enough data to say that we can establish efficacy for autism more broadly,” but said the agency is open to interest from companies studying leucovorin in the autism population.

The drug, also known as folinic acid, is a synthetic form of vitamin B9 that is used to treat the toxic side effects of chemotherapy. A few small trials have suggested that leucovorin may be effective as an off-label treatment for children with autism, and some families have reported that it has helped their nonverbal children develop more language and social skills.

FDA officials, who requested anonymity to discuss the decision, told reporters Monday that they began with a broad review of leucovorin as an autism treatment, narrowing its approval to a small population with cerebral folate deficiency, a rare genetic mutation that prevents folate from being properly absorbed.

The condition shares overlapping symptoms with autism, usually develops in young children under 2 years of age, and can lead to severe developmental delays, seizures, lack of muscle control, and other serious neurological complications.

The FDA found that using leucovorin in patients with that condition produced “high-quality data” to support expanded approval, which applies to both generic versions of the drug and GSK’s older brand drug, velcovorin, officials said.

“That’s the data we’ve seen with the largest effect sizes,” an FDA official said on the call. “So we narrowed down that population, because it has a strong scientific rationale and a large treatment effect that can be used to overcome some of the limitations in the data sources.”

The approval was based on a systematic review of the published literature in the area, including patient case reports, but not a randomized controlled clinical trial. The same official acknowledged that there can be biases with systematic reviews, but emphasized that the treatment effects are so large that they outweigh those concerns.

Officials added that the FDA is encouraging existing manufacturers of leucovorin to ramp up production to match increased demand for the drug. While GSK originally sold the drug from 1983 to 1997, the company said in September it had no plans to restart and manufacture the product.

In a release on Tuesday, Dr. Tracy Beth Hoeg, executive director of the FDA’s Center for Drug Evaluation and Research, said the approval demonstrates the FDA’s commitment to “rapidly identifying effective treatments for ultra-rare diseases and maintaining the same evidence-based standards for approval.”