Objective: To present 3-year safety and clinical outcome data from a phase 1b, open-label trial of VY-AADC01 (NBIb-1817) for Parkinson’s disease (PD) patients with motor fluctuations.

Background: PD-1102 is a 3-year, open-label trial of VY-AADC01, an investigational AAV2 gene therapy encoding human aromatic L-amino acid decarboxylase (AADC), administered using a posterior approach to bilateral putamen. In a prior phase 1b trial (PD-1101), where increasing doses of VY-AADC01 were administered via a frontal approach, both clinician- and participant-reported clinical outcomes were stable or improved across trial cohorts through 3 years [1].

Method: Eight participants with PD were administered ≤9.4×10¹² vector genomes (≤1800 µL/hemisphere) of VY-AADC01 using convection-enhanced delivery and intraoperative MRI monitoring, to infuse ≥50% of each putamen via a single posterior (parieto-occipital) trajectory. Seven of 8 participants have completed the 36-month assessment; UPDRS was not assessed in 3 due to Covid. Data presented are mean±SD change from baseline.

Results: At baseline, mean PD duration was 9.2 years; modified Hoehn and Yahr scores were 2.5 (n=4) and 3 (n=4). Posterior administration of VY-AADC01 achieved putaminal coverage of 53.5±7.0%. No VY-AADC01-related SAE has been reported through the last follow-up; as reported previously, 2 participants had grade 1 intraoperative intracerebral hemorrhage (resolved, no residual deficit). One of the 7 participants received DBS 13m post-VY-AADC01 (for incomplete control of wearing off dystonia; data reported with stimulation on). At 36m, the daily levodopa equivalent dose was reduced by ‑205.6±442.7mg, while diary good ON time (ON time with no + non-troublesome dyskinesia) increased by 0.9±2.4h and diary OFF time decreased by ‑1.7±1.9h. In the 4 participants with available data, UPDRS III scores off medication decreased (improved) by ‑12.0±6.2 and scores on medication remained largely unchanged (2.0±6.68). PDQ-39 scores decreased (improved) by ‑5.3±16.5.

Conclusion: Administration of VY-AADC01 to the putamen delivered via a posterior approach was well tolerated. Relative to baseline, 3-year data show a reduction in daily PD medication, stable or improved motor function, and improved quality of life. These results are consistent with data from the 2 higher-dose cohorts of the PD-1101 trial [1].

References: 1. C. Christine, R. Richardson, A. Van Laar, M. Thompson, K. Herbert, C. Li, G. Liang, E. Fine, P. Larson. Three-year safety and clinical outcomes from the PD-1101 trial of AADC gene therapy for advanced Parkinson’s disease [Abstract 879]. Movement Disorders. 2020;35(1): S391

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-pd-1102-trial-in-advanced-parkinsons-disease-safety-and-clinical-outcomes-from-a-3-year-phase-1b-study-of-aadc-gene-therapy-administered-via-a-posterior-approach/