Objective: To report 18-month safety and clinical outcomes from a phase 1, open-label trial of VY-AADC01 (NBIb-1817) for Parkinson’s disease (PD) patients with motor fluctuations.

Background: VY-AADC01 is an investigational AAV2 gene therapy encoding human aromatic L-amino acid decarboxylase (AADC). In an earlier phase 1 trial (PD-1101), VY-AADC01 was administered via a frontal approach using ≥2 trajectories per putamen. PD diary measures and UPDRS III scores off medication were improved over baseline with up to 36 months of follow-up.¹

Method: Eight participants were administered ≤9.4×10¹² vector genomes of VY-AADC01 via a single posterior (occipital-parietal) trajectory to each putamen with intraoperative MRI monitoring. The putaminal coverage target was ≥50%. Preliminary 18-month data are reported as mean±SEM absolute change from baseline and percent change from baseline.

Results: Mean PD duration at baseline was 9.2 years and modified H&Y scores were 2.5 (n=4) or 3 (n=4). Posterior administration of VY-AADC01 was achieved in all participants, and mean putaminal coverage was 53.5%. No SAE have been reported through last follow-up. As previously described, 2 participants experienced grade 1 intraoperative intracerebral hemorrhage, which resolved without residual deficits. One participant received DBS 13 months post VY-AADC01 administration due to incomplete improvement of severe wearing off dystonia. PD medication requirements were reduced (levodopa-equivalent dose, −552.9±142.9 mg [−37%]), with stable to improved motor function. Diary good ON time (ON time including non-troublesome dyskinesia but excluding troublesome dyskinesia) increased by 1.2±1.0 hrs (14%); diary OFF time decreased by −1.8±0.9 hrs (−26%). UPDRS III scores off medication improved by −10.5±3.45 (−30%), while scores on medication remained relatively stable (−1.5±2.0 [−13%]). Excluding the participant who received DBS had minimal impact on the findings. Updated data will be reported.

Conclusion: VY-AADC01 administered using a single posterior trajectory per putamen was well tolerated. Average daily PD medication doses were substantially reduced, and study participants showed stable or improved motor function 18 months following VY-AADC01 administration. These findings were consistent with those observed in the 2 higher-dose cohorts of the PD-1101 trial.¹

References: 1. Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, Kells AP, et al. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson’s disease. Ann Neurol. 2019;85(5):704-14.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/aadc-gene-therapy-administered-via-a-posterior-approach-18-month-results-from-the-pd-1102-trial-in-advanced-parkinsons-disease/