OBJECTIVES: AADCd is a rare, infantile-onset, neurometabolic disorder, characterized by motor dysfunction and developmental delays. Clinical trials of the gene therapy eladocagene exuparvovec (EE) have shown meaningful improvements in motor function as measured by Total Peabody Developmental Motor Scales-Second Edition (PDMS-2) score. This study is a cost-effectiveness analysis of EE compared to best supportive care (BSC) for the treatment of patients with AADCd, from a US perspective.

METHODS: Multi-state modeling was conducted for achieving multiples of the meaningful score difference (MSD) for Total PDMS-2 score in AADCd, previously estimated at 40 points in analysis anchoring against changes in motor milestones (MM). Multiples of the MSD were mapped to the corresponding MM states: “full head control”, “sitting unassisted”, “standing with support”, and “walking with assistance”. All patients started from the “no motor function” state. Cumulative incidence of achieving each multiple of the MSD, conditional on the prior multiple, was modeled. An alternative approach modeled cumulative incidence of MM achievement. Utilities were from a US time-trade-off study valuing the quality-of-life impact of AADCd by MM state. Results are presented undiscounted.

RESULTS: Data from 30 patients (3 EE clinical trials) were analyzed; 87% had follow-up ≥2 years. Multi-state modeling based on multiples of the Total PDMS-2 MSD indicated incremental (i.e., difference of EE vs. BSC) life-year (LY) gains of 36.00 and quality-adjusted life-year (QALY) gains of 40.10. Modeling MM achievement, incremental LY gains were 30.55 and QALY gains were 34.84.

CONCLUSIONS: This study suggests that patients have significant LY and QALY gains with EE treatment compared to BSC, indicating that EE is a transformative treatment for AADCd. Strengths included alternative approaches to model motor function, with consistent findings across models. Moreover, use of the Total PDMS-2 score MSD provides a more responsive measure of motor-function improvements in AADCd than MM achievement alone.