The FDA announced (here) that it has approved leucovorin calcium for “cerebral folate deficiency (CFD), a neurological condition that affects folate (a vitamin essential for brain health) transport into the brain. Individuals with cerebral folate deficiency have been observed to have developmental delays with autistic features (e.g., challenges with social communication, sensory processing, and repetitive behaviors), seizures, and problems with movement and coordination,” but not for autism.
The FDA had originally suggested that it would ask the innovator, GSK, to seek the autism indication for leucovorin calcium but, in reviewing the actual data, the Agency agreed that it did not support that broad of an indication. This is a much narrower indication than Secretary Kennedy and the FDA Commissioner originally sought but, based on the review of the data, the CFD indication is only approved for use in patients who have a confirmed variant in the folate receptor 1 (FOLR1) gene. This is a small subset of CFD patients. Angus Liu and Darren Incorvaia report in Fierce Pharma (here) that “CFD-FOLR1 is an ultrarare genetic form of CFD, which is present in some children with autism spectrum disorder, affecting, according to a senior FDA official, less than 1 in a million people. CFD is a neurological condition characterized by the inability of folate to cross the blood-brain barrier, leading to symptoms such as seizures, motor issues and intellectual disability. Besides FOLR1 mutation, other causes of CFD include autoantibodies blocking the folate receptor.”
Of the 27 patients who got oral leucovorin calcium only, the FDA-approved labeling describes data indicating “‘a range of clinical improvements in various neurological symptoms’ for 24 (89%) individuals, while the remaining three showed either no change or no progression of symptoms.”
