NCATS Researchers Help Gene Therapy for AADC Deficiency Gain FDA Approval

NCATS’ Therapeutics for Rare and Neglected Diseases program helped develop a recently approved gene therapy for a rare brain disorder. The U.S. Food and Drug Administration approved Kebilidi (from PTC Therapeutics) to treat aromatic L-amino acid decarboxylase deficiency, a devastating, fatal genetic disease. (Shutterstock)

Dec. 13, 2024

NCATS’ Therapeutics for Rare and Neglected Diseases (TRND) program helped develop a recently approved gene therapy for a rare genetic brain disorder. The U.S. Food and Drug Administration (FDA) approved Kebilidi (from PTC Therapeutics) to treat aromatic L-amino acid decarboxylase (AADC) deficiency, a devastating, fatal genetic disease. Initially approved in Europe as Upstaza, Kebilidi is the first gene therapy to be delivered directly to the brain.

AADC deficiency occurs when mutations in a gene lead to a reduction in key chemical messengers in the brain and other parts of the central nervous system. The gene defect results in developmental delays, seizures and severe disabilities. Kebilidi uses an adeno-associated virus to deliver a functional copy of the gene to brain cells and restore the missing AADC enzyme.

In 2016, TRND scientists teamed with researchers from Agilis Biotherapeutics Inc. to move the gene therapy closer to regulatory approval. Previous clinical studies in Taiwan showed the therapy’s potential effectiveness in young children, but key data required by the FDA were missing. Agilis and TRND conducted preclinical safety studies, developed and validated production methods, and conducted biostatistical analyses of the existing clinical data. PTC Therapeutics later acquired Agilis and completed the studies needed to bring this treatment to patients worldwide.

“This collaboration between Agilis and TRND came at a critical time to help bridge the development gaps needed to advance this therapy,” said Elizabeth Ottinger, Ph.D., Acting Director of the NCATS Therapeutic Development Branch. “We are now seeing the downstream impact of this early interaction.”

View a related story on NCATS’ AADC work.