Improved Motor Function in Children With Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency Treated With Eladocagene Exuparvovec (PTC-AADC): Interim Findings From a Phase 1/2 Study
Paul Wuh-Liang Hwu1, Yin-Hsiu Chien1, Ni-Chung Lee1, Sheng-Hong Tseng1, Mark Pykett2, Chun-Hwei Tai1
1National Taiwan University Hospital, 2PTC Therapeutics , Inc.,
Objective:
We report interim findings from a study evaluating efficacy and safety of PTC-AADC, a recombinant adeno-associated virus vector containing human cDNA encoding AADC.
Background:

AADC deficiency is caused by mutations in the gene encoding the enzyme AADC, resulting in dopamine deficiency and movement disorders. Current treatments fail to restore dopamine levels and improve motor function.

Design/Methods:

This is a 2-year interim analysis from a 5-year, phase 1/2, prospective, open-label study in AADC deficiency using bilateral intraputaminal injections of 1.8 × 1011 vg 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 Bayley-III , 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 39.9 months.

Results:
Of 10 patients treated, 1 withdrew at 11 months (influenza B encephalopathy leading to death). Others completed follow-up through year 2. Two years post-treatment, 50% of patients achieved full head control, 33% were able to sit unassisted, and 22% could stand with support. Mean PDMS-2 total score increased significantly from baseline at 24 months. Similar trends were seen with AIMS and Bayley-III total scores. Hypotonia, oculogyric crises, limb dystonia, and stimulus-provoked dystonia decreased. Mean putaminal 18F-DOPA uptake increased by year 1 through year 2. No viral shedding was detected. All patients experienced ≥1 TEAE (mostly mild or moderate); none were considered definitely treatment related. 27/131 TEAEs were possibly treatment related, including 18 dyskinesia episodes; most resolved within 6 months. 
Conclusions:
Children with AADC deficiency achieved improvements in motor function after intraputaminal PTC-AADC therapy. No new safety signals were identified. These findings support the efficacy and safety of PTC-AADC in AADC deficiency.