Neurology | 2019
AGIL-AADC Gene Therapy Results in Sustained Improvements in Motor and Developmental Milestones Over 5 Years in Children With AADC Deficiency (P4.6-058)
Abstract
Objective: To evaluate clinical outcomes through 5 years in children with aromatic l-amino acid decarboxylase (AADC) deficiency treated with AGIL-AADC, a recombinant adeno-associated virus vector containing the human cDNA encoding the AADC enzyme. Background: AADC deficiency is a rare genetic disorder of neurotransmitter synthesis. In this update, we present 2-year posttreatment data with AGIL-AADC in 18 patients, and 5-year posttreatment data for 8 patients. Design/Methods: In 2 single-arm, open-label clinical studies, children with AADC deficiency received AGIL-AADC (total dose, 1.8×1011 vg) as bilateral, intraputaminal, stereotactic infusions during a single operative session. The primary endpoint was achievement of motor developmental milestones on the Peabody Developmental Motor Scale, Second Edition (PDMS-2; total and single-item subscale scores). Total and subscale scores on the Alberta Infant Motor Scale (AIMS) and Bayley-III also assessed developmental milestones. De novo dopamine production was evaluated with F-DOPA PET imaging. Adverse events (AEs) were recorded. Findings were compared with a natural history cohort of severe AADC patients (N=82) using the Fisher exact test (α=0.05). Results: Patients aged 21 months to 8.5 years (N=18) received AGIL-AADC. None had full head control or could sit unassisted or stand at baseline. At the time of this analysis, all patients had 2 years of posttreatment data; 8 patients had 5 years of posttreatment data. Clinically meaningful improvements were observed in PDMS-2 total score and single-item motor developmental milestones versus natural history controls. Improvements were observed in AIMS scores and Bayley-III total and cognitive and language subscale scores. All patients demonstrated sustained de novo dopamine production. All AEs were associated with the disease; no new safety signals were observed over 5 years. Conclusions: In children with AADC deficiency, AGIL-AADC gene therapy achieved clinically meaningful, sustained improvements in motor, cognitive, and language milestones for up to 5 years, with no new safety signals identified Disclosure: 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. Conway has received compensation for serving on the Board of Directors of Agilis Biotherapeutics. Dr. Conway holds stock and/or stock options in 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. (previously Agilis Biotherapeutics). Dr. Pykett has received compensation for serving on the Board of Directors of Agilis Biotherapeutics, Serene, and Hemogenyx. Dr. Pykett holds stock and/or stock options in PTC Therapeutics (previously Agilis Biotherapeutics). Dr. Hwu has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Hwu has received research support from Biogen.