The primary objectives of this open-label study were to assess the pharmacodynamics of eladocagene exuparvovec and the safety of the SmartFlow magnetic resonance (MR)-compatible ventricular cannula for administering eladocagene exuparvovec in pediatric participants with ?-amino acid decarboxylase (AADC) deficiency.

Eladocagene exuparvovec gene therapy, delivered via bilateral intraputaminal infusion, has been evaluated in participants with the rare neurotransmitter disorder AADC deficiency in three clinical trials.

Thirteen children (aged 16–129 months) with AADC deficiency received eladocagene exuparvovec using the SmartFlow MR-compatible ventricular cannula in this phase 2 multicenter open-label trial in the USA, Israel and Taiwan. Cerebrospinal fluid (CSF) homovanillic acid (HVA) levels and intraputaminal uptake of [¹⁸F] fluorodopa (F-DOPA) were assessed at week 8 to evaluate pharmacodynamic evidence of dopamine production. Safety and tolerability of the cannula used for gene therapy delivery were assessed over 8 weeks.

Baseline mean (SD) age of the 13 participants was 45.2 (29.5) months. All participants showed motor developmental delay. Floppiness was recorded as severe, moderate or mild in nine (69.2%), two (15.4%) and two (15.4%) participants, respectively. Post-gene therapy, mean (SD) CSF HVA levels increased significantly from 22.5 (32.3) nmol/L at baseline to 53.9 (44.4) nmol/L at week 8 (p<0.001). F-DOPA levels increased significantly from 0.098 (0.074) at baseline to 0.343 (0.040) at week 8 (p<0.001). Common adverse events (AEs) recorded in >20% of participants in the 8 weeks post-gene therapy included pyrexia, dyskinesia, hypotension, anemia, diarrhea, hypokalemia and hypophosphatemia. Treatment-emergent AEs were deemed unrelated (n=12 participants) or unlikely related (n=1 participant) to the SmartFlow MR-compatible surgical device.

CSF HVA levels and F-DOPA uptake increased significantly 8 weeks post-eladocagene exuparvovec gene therapy in pediatric participants with AADC deficiency, indicating dopamine production. No treatment-emergent AEs were deemed related to the SmartFlow MR-compatible surgical device used for gene therapy delivery.