Additional Coverage:
FDA Approves Expanded Use of Leucovorin Calcium for Rare Neurological Disorder
**Washington D.C. ** – The U.S.
Food and Drug Administration (FDA) has announced the approval of leucovorin calcium tablets for the treatment of cerebral folate deficiency (CFD), a rare neurological condition. This marks a significant development for patients living with this challenging disorder, which previously lacked an FDA-approved treatment.
Leucovorin calcium, a synthetic form of vitamin B9, has historically been utilized to mitigate the toxic side effects of chemotherapy. The recent FDA approval is based on a comprehensive review of published literature, including detailed case reports and mechanistic data, as outlined in an agency press release.
Cerebral folate deficiency is characterized by impaired folate transport into the brain, leading to a range of severe neurological complications. Individuals with CFD-FOLR1 often experience significant developmental delays, movement disorders, seizures, and other serious neurological issues. The National Organization for Rare Disorders indicates that fewer than 20 cases of CFD have been documented in scientific literature, highlighting its extreme rarity and the unknown exact prevalence.
While the Trump administration previously highlighted leucovorin as a potential treatment for autism, the FDA has clarified that current research is insufficient to establish its efficacy for the broader autism population. An FDA official stated that there isn’t “sufficient data to say that we could establish efficacy for autism more broadly,” though the agency remains open to further studies on leucovorin in the autism community.
The American Academy of Pediatrics (AAP) echoes this sentiment, noting that evidence supporting its use in autistic children is limited. However, the AAP acknowledges that “small studies show benefits to communication and behavior for some autistic children, specifically those with CFD or evidence of folate metabolic differences,” and calls for larger, independent trials.
FDA Commissioner Marty Makary emphasized the importance of this approval, stating, “Today’s approval represents a significant milestone for patients living with cerebral folate transport deficiency due to the FOLR1 variant, a rare genetic condition that has had no FDA-approved treatment options until today.” Makary added that this action “may benefit some individuals with FOLR1-related cerebral folate transport deficiency who have developmental delays with autistic features.”
FDA officials revealed that their initial review explored leucovorin as an autism treatment before narrowing the approval to the specific population with cerebral folate deficiency. This decision was driven by the observation of “the largest effect sizes” within this group, providing a stronger scientific rationale and more substantial treatment effects, despite relying on systematic reviews rather than randomized trials. Officials noted that the significant treatment effects outweighed potential biases associated with such reviews.
The FDA is now encouraging manufacturers to increase the production of leucovorin. Notably, GSK, which originally marketed the drug from 1983 to 1997, has indicated no plans to resume its manufacture.