Objective: To present preliminary 3-year data from the PD-1101 trial of VY-AADC01 for advanced Parkinson’s disease (PD) with motor fluctuations.

Background: This 3-year phase 1b open-label trial is investigating targeted putaminal delivery of VY-AADC01, an experimental AAV2 gene therapy encoding human aromatic L-amino acid decarboxylase (AADC). Interim results, including 3-year data from the first of 3 study cohorts, have been published.¹

Method: Bilateral, intraoperative MRI-guided putaminal infusions of VY-AADC01 were administered to 3 cohorts (n=5 participants per cohort) in ascending doses: cohort 1, ≤7.5×10¹¹ vector genomes (vg); cohort 2, ≤1.5×10¹² vg; cohort 3, ≤4.7×10¹² vg. Mean (±SEM) changes from baseline at 3 years are reported here for cohorts 2 and 3.

Results: No serious adverse events (SAEs) attributed to VY-AADC01 have been reported. All 4 non-drug–related SAEs (atrial fibrillation and pulmonary embolism in one participant¹ and two small intestinal obstructions in another participant) resolved. Requirements for PD medications were reduced in cohorts 2 and 3 (levodopa-equivalent dose reductions, −608.5±243.3 and −440.7±72.6 mg, respectively), with motor function and quality of life improved or stable. PD diary good ON time (ON time without troublesome dyskinesia) increased by 2.2±1.7 hr in cohort 2 and 0.3±0.7 hr in cohort 3; OFF time decreased by −1.9±0.5 hr in cohort 2 and −0.15±0.9 hr in cohort 3.  UPDRS III scores on and off medication improved: −7.8±1.6 and −12.2±3.3, respectively, in cohort 2; −3.8±1.5 and −10.2±4.6, respectively, in cohort 3. PDQ-39 scores decreased by −5.6±1.9 in cohort 2 and −2.15±8.1 in cohort 3. Three-year clinical outcomes in cohorts 2 and 3 were consistent with those reported at earlier timepoints,¹ demonstrating the durability of response over time.

Conclusion: Three years after VY-AADC01 administration, participants in cohorts 2 and 3 of the PD-1101 trial for advanced PD continued to require substantially less antiparkinsonian medications and showed stable or improved motor function and quality of life.

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/three-year-safety-and-clinical-outcomes-from-the-pd-1101-trial-of-aadc-gene-therapy-for-advanced-parkinsons-disease/