The U.S. Food and Drug Administration (FDA) has granted accelerated approval to Kebilidi™ (eladocagene exuparvovec-tneq), a 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.
Mechanism of Action
AADC deficiency is a rare genetic disorder that impairs the synthesis of dopamine, a crucial neurotransmitter for motor function. Kebilidi is a gene replacement therapy designed to deliver a functional DDC gene directly into the putamen of the brain via a stereotactic neurosurgical procedure. This increases the AADC enzyme levels and restores dopamine production.
Clinical Trial Results
The accelerated approval was based on safety and efficacy data from an ongoing global clinical trial (PTC-AADC-GT-002). Results showed that Kebilidi facilitates the de novo synthesis of dopamine, leading to progressive improvements in motor development milestones. Continued approval is contingent upon verification and description of clinical benefit in a confirmatory trial.
Adverse Reactions
The most common adverse reactions (≥15%) observed in patients treated with Kebilidi were dyskinesia (77%), pyrexia (38%), hypotension (31%), anemia (31%), salivary hypersecretion (23%), hypokalemia (23%), hypophosphatemia (23%), insomnia (23%), hypomagnesemia (15%), and procedural complications, including respiratory and cardiac arrest (15%).
Dosing and Administration
Kebilidi is administered via a stereotactic surgical procedure by a qualified neurosurgeon in specialized centers. The therapy involves a minimally invasive neurosurgical approach to deliver the gene therapy directly into the putamen.
About AADC Deficiency
AADC deficiency is a severe and often fatal genetic disorder that causes significant disability from early infancy. Affected children may experience oculogyric crises, developmental delays, and complications requiring extensive medical intervention. Current treatments involve managing symptoms, but Kebilidi addresses the underlying genetic cause.
Company Statement
"PTC has once again pioneered a new approach to treating highly morbid neurologic diseases," said Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics. "I am proud of our team's unwavering commitment to achieve this important regulatory milestone. We look forward to bringing this transformational gene therapy to children and adults with AADC deficiency in the United States."
