FDA Approves Direct-to-Brain Gene Therapy for AADC Deficiency

November 14, 2024

The Food and Drug Administration has granted accelerated approval for eladocagene exuparvovec-tneq (Kebilidi, PTC Therapeutics), the first gene therapy for aromatic L-amino acid decarboxylase (AADC) deficiency, a rare and life-threatening genetic disorder. This approval represents the first FDA-approved gene therapy administered directly to the brain.

AADC deficiency is caused by mutations in the DDC gene that results in the inability to synthesize dopamine and leads to severe developmental delays and neurological abnormalities. Symptoms often appear within the first few months of life.

Eladocagene exuparvovec-tneq is an adeno-associated virus (AAV) vector-based therapy that delivers a functional copy of the DDC gene directly to cells in the putamen, a region of the brain involved in motor control. It is administered in a single surgical session via four infusions and requires a medical center specializing in pediatric stereotactic neurosurgery. Once infused, it promotes AADC enzyme expression and increases dopamine levels, aiding in movement, attention, learning and memory.

FDA based its approval on data from an open-label, single-arm clinical study in 13 pediatric patients with confirmed diagnosis of AADC deficiency and no gross motor function. Treatment with eladocagene exuparvovec-tneq led to gross motor function improvement in 8 of 12 patients available for assessment. The most common adverse reactions were dyskinesia, fever, low blood pressure and anemia. It is contraindicated in patients who have not achieved skull maturity, as assessed by neuroimaging.

The application received priority review designation, orphan drug designation and a rare pediatric disease priority review voucher. Additionally, FDA authorized SmartFlow Neuro Cannula, an infusion tube inserted into a target in the brain, to deliver the therapy.