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 certain adults and children.
The move comes months after the Trump administration touted leucovorin as a potential therapy for a broader group of patients with symptoms of autism spectrum disorder. The claim generated skepticism among some members of the medical and research community, but fueled enthusiasm among families, increasing prescriptions of the drug in the US.
An FDA official told reporters Monday that “we don't have enough data to say we could establish efficacy for autism more broadly,” but said the agency is open to companies' interest in studying leucovorin in the autism population.
The drug, also known as folinic acid, is a synthetic form of vitamin B9 that has been used to treat the toxic side effects of chemotherapy. Only a few small trials have suggested that leucovorin might be effective as an off-label treatment for children with autism, and some families have reported that it helped their nonverbal children develop more social and language skills.
FDA officials, who requested anonymity to discuss the decision, told reporters Monday that they began a broad review of leucovorin as a treatment for autism before limiting its approval to a smaller population with brain folate deficiency, a rare genetic mutation that prevents folate (a key vitamin) from properly reaching the brain.
The condition shares overlapping features with autism, typically developing in young children under the age of 2, and can cause severe developmental delays, seizures, lack of muscle control, and other serious neurological complications.
Officials said the FDA found that the use of leucovorin in patients with that condition produced “the highest quality data” to support an expanded approval, which will apply to both generic versions of the drug and GSK's former brand-name drug, Wellcovorin.
“Those were the data where we saw the largest effect sizes,” an FDA official said on the call. “So we limited ourselves to that population, simply because we felt that was the strongest scientific rationale and also the largest treatment effects that could be used to then overcome some of the limitations of the data sources.”
The approval was based on a systematic review of published literature in the area, including patient case reports, but not a randomized controlled clinical trial. The same official acknowledged that there may be bias in systematic reviews, but emphasized that the treatment effects were so large that they outweighed those concerns.
The FDA is encouraging existing leucovorin manufacturers to increase production to meet increased demand for the drug, officials added. While GSK originally marketed the drug between 1983 and 1997, the company said in September that it has no plans to relaunch and manufacture the product.
In a statement Tuesday, Dr. Tracy Beth Hoeg, acting 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 while maintaining the same evidentiary standards for approval.”
