Improved Motor Function in Children With Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency Treated With Eladocagene Exuparvovec (PTC-AADC): Compassionate Use Study (2387)

Objective: This 5-year study evaluated efficacy and safety of PTC-AADC, a recombinant adeno-associated virus containing cDNA encoding AADC, in children with AADC deficiency. Background: AADC deficiency is a rare inherited disorder caused by mutations in the DDC gene. Resulting deficiencies of neurotransmitters impede motor development within the first months of life. Current treatments yield little improvement. Gene therapy has been proposed to treat this disorder. Design/Methods: This observational study evaluated data from a single-arm, compassionate-use study enrolling children aged >2 years with AADC deficiency (n=8) receiving intraputaminal PTC-AADC. Primary efficacy end point was proportion achieving key milestones using Peabody Developmental Motor Scale, Second Edition (PDMS-2), vs historical controls (n=82). Secondary end points included changes in PDMS-2, Alberta Infant Motor Scale (AIMS), and Comprehensive Developmental Inventory for Infants and Toddlers (CDIIT) scores, and body weight. Pharmacodynamic end points included putaminal 18F-DOPA uptake on PET. Safety end points included treatment-emergent adverse events (TEAEs) and viral shedding. Mean follow-up was 62.5 months. Results: No enrolled patients had achieved any motor milestones at baseline. Five years after treatment, 4/8 patients exhibited full head control and could sit unassisted (P=0.0002 vs control); 2/8 stood with support (P=0.045 vs control). Mean PDMS-2, AIMS, and CDIIT total scores (all P Conclusions: Children with AADC deficiency achieved sustained improvements in motor function after PTC-AADC, with increased putaminal dopamine production. No new safety signals were identified. Disclosure: Maria Manuel Brites has nothing to disclose. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis/Norvatis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Yin-Hsiu Chien has received research support from Biogen. The institution of Yin-Hsiu Chien has received research support from Sanofi Genzyme. Ni-Chung Lee has nothing to disclose. Sheng-Hong Tseng has nothing to disclose. Mark Pykett has received personal compensation for serving as an employee of PTC Therapeutics. Mark Pykett has received personal compensation in the range of $500,000-$999,999 for serving as an officer or member of the Board of Directors for PTC Therapeutics. Mark Pykett has received stock or an ownership interest from PTC Therapeutics. Mark Pykett has received personal compensation in the range of $10,000-$49,999 for serving as a Observer with Pharming Group. The institution of Chun-Hwei Tai has received research support from National Taiwan University Hospital.