The U.S. Food and Drug Administration has approved an expanded use of Wellcovorin (leucovorin calcium) tablets to treat cerebral folate deficiency in adults and children with a confirmed variant in the folate receptor 1 gene (CFD-FOLR1). This marks the first FDA-approved therapy for the rare genetic condition.

 

"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,” said FDA Commissioner Marty Makary. “This action may benefit some individuals with FOLR1-related cerebral folate transport deficiency who have developmental delays with autistic features.”

 

The approval comes after a systematic review of published literature, including patient-level case reports and mechanistic data. Cerebral folate deficiency is a neurological disorder that disrupts folate—a vitamin critical for brain health—from entering the brain. Those affected often face severe developmental delays, movement disorders, seizures, and other serious neurological complications.

 

The FDA worked closely with GSK, the New Drug Application holder for Wellcovorin, to update the drug’s labeling with essential scientific information for safe and effective use in both adult and pediatric patients.

 

"The approval of leucovorin for FOLR1-related cerebral folate transport deficiency (CFD-FOLR1) demonstrates the FDA’s commitment to rapidly identifying effective treatments for ultra rare diseases while maintaining the same evidentiary standards for approval,” said Tracy Beth Hoeg, MActing Director of the FDA’s Center for Drug Evaluation and Research. 

 

“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.”

 

Patients should be aware of potential side effects, which include itching, rash, hives, difficulty breathing, sudden chills, and temperature regulation issues. Severe allergic reactions such as anaphylaxis require immediate medical attention.

 

The FDA said today’s approval addresses a critical need for individuals with CFD-FOLR1 and reinforces its commitment to advancing health for all Americans, including those affected by rare genetic conditions.