The US Food and Drug Administration has approved expanded use of Wellcovorin (leucovorin calcium) tablets for the treatment of cerebral folate deficiency in adult and pediatric patients with a confirmed FOLR1 variant. The approval marks the first FDA-approved treatment for cerebral folate deficiency associated with FOLR1 variants, a rare genetic disorder that impairs folate transport into the brain.

Cerebral folate deficiency is a neurologic condition characterized by impaired transport of folate, a vitamin essential for brain development and function, into the brain. Patients with folate receptor 1–related disease may experience severe developmental delays, movement disorders, seizures, and other neurologic complications. The newly approved indication applies to Wellcovorin (leucovorin calcium) for patients with confirmed variants in the folate receptor 1 gene.

The approval was supported by a systematic review of published scientific literature, including case reports with patient-level data and mechanistic evidence describing the drug’s biological activity. According to the FDA, these data demonstrated clinical benefit compared with the expected natural history of the disease.

FDA Commissioner Marty Makary, MD, MPH, said, “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.” He added that the therapy “may benefit some individuals with FOLR1-related cerebral folate transport deficiency who have developmental delays with autistic features.”

The agency collaborated with GSK, the holder of the New Drug Application for Wellcovorin, to update the product labeling with information supporting safe and effective use of leucovorin in adult and pediatric patients with cerebral folate deficiency associated with folate receptor 1 variants.

“It also provides a good example of how observational or ‘real world’ evidence can lead to an FDA approval when the product is shown to provide clear clinical benefit compared with what is seen with the natural history of the disease, remarked Tracy Beth Hoeg, MD, PhD, acting director of the FDA Center for Drug Evaluation and Research.

Adverse reactions associated with leucovorin may include pruritus, rash, urticaria, dyspnea, rigors, and impaired thermoregulation. Anaphylaxis, a severe allergic reaction requiring immediate medical attention, has also been reported.

Source: FDA