Safety and Improved Efficacy Outcomes in Children AADC Deficiency Treated with Eladocagene Exuparvovec Gene Therapy: Results From Three Clinical Trials (4688)

Objective: To evaluate clinical outcomes in children with aromatic l-amino acid decarboxylase (AADC) deficiency treated with eladocagene exuparvovec, a recombinant adeno-associated virus vector containing the human cDNA encoding the AADC enzyme. Background: AADC deficiency, a rare genetic disorder of neurotransmitter synthesis, is characterized by motor developmental deficits and clinical features associated with the autonomic nervous system, including dyskinesia, oculogyric crisis, and feeding/swallowing problems. Design/Methods: In 3 open-label clinical studies, children with AADC deficiency who had no full head control and no ability to sit, stand, or walk received eladocagene exuparvovec as bilateral, intraputaminal, stereotactic infusions during a single operative session (total dose, 1.8×1011 vg). Body weight, oculogyric crisis episodes, and adverse events (AEs) were recorded. Results: In the 3 studies, patients aged 21 months to 8.5 years (N=26) received eladocagene exuparvovec, constituting the safety population. In the intent-to-treat population (N=21), mean body weight at baseline was 12.0 kg (median 10.5 kg) and increased to 15.2 kg (median 13.2 kg) at 12 months posttreatment. Frequency of oculogyric crises was improved at 12 months posttreatment. Dyskinesia was recorded as an AE in 23 patients in the safety population; most events were mild or moderate, occurred within 3 months after eladocagene exuparvovec treatment, generally responded to standard pharmacotherapy, and resolved in all patients by 10 months Conclusions: In children with AADC deficiency who received eladocagene exuparvovec gene therapy, body weight increased and oculogyric crises and dyskinesia improved. Disclosure: Dr. Hwu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Hwu has received research support from PTC Therapeutics, Inc. Dr. Chien has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Tseng has nothing to disclose. Dr. Tai has nothing to disclose. Dr. Conway has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc. Dr. Pykett has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PTC Therapeutics, Inc.