The U.S. Food and Drug Administration (FDA) has approved Kebilidi (eladocagene exuparvovec-tneq), a one-time gene therapy developed by PTC Therapeutics, for the treatment of aromatic L-amino acid decarboxylase (AADC) deficiency in both children and adults. This marks the first gene therapy approved in the United States that is directly administered to the brain.
Addressing a Critical Neurological Deficit
AADC deficiency is a rare, life-threatening genetic disorder caused by mutations in the DDC gene, which impairs the production of the AADC enzyme. This enzyme is crucial for synthesizing neurotransmitters like dopamine, essential for motor function and neurological signaling. The deficiency leads to severe developmental delays, movement disorders, and other disabilities.
Kebilidi utilizes an adeno-associated virus (AAV2) vector to deliver a functional copy of the DDC gene directly into the putamen region of the brain. This enables brain cells to produce the AADC enzyme, restoring dopamine production and alleviating disease symptoms.
Clinical Evidence and Accelerated Approval
The FDA's accelerated approval of Kebilidi is based on data from multiple clinical studies, including Phase 1/2 (NCT01395641) and Phase 2b (NCT02926066) trials, as well as a compassionate use program. These studies demonstrated that Kebilidi treatment led to improvements in motor function and reduced symptom severity in patients with AADC deficiency.
PTC Therapeutics' application for Kebilidi was granted priority review, expediting the review process. The approval is contingent upon the verification and description of clinical benefit in confirmatory trials involving long-term follow-up of treated patients.
Administration and Safety Considerations
Kebilidi is administered via a one-time stereotactic neurosurgical procedure, requiring specialized centers and trained neurosurgeons. The procedure involves direct infusion of the gene therapy into the putamen using the SmartFlow Neuro Cannula device.
Adverse reactions reported in clinical trials include dyskinesia, pyrexia, hypotension, and procedural complications. The therapy is contraindicated in patients who have not achieved skull maturity, as assessed by neuroimaging.
Impact and Future Directions
"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," said Matthew B. Klein, MD, CEO of PTC Therapeutics. The company is now focused on launching Kebilidi in selected specialist centers, with surgeons already trained to administer the gene therapy.
This approval not only provides a new treatment option for AADC deficiency but also highlights the potential of gene therapy for addressing other neurological disorders. PTC Therapeutics received a Rare Disease Priority Review Voucher, which can expedite the review of future therapies targeting rare diseases.
