Eladocagene Exuparvovec for the Treatment of Aromatic L-Amino Acid Decarboxylase Deficiency (AADCd): An Economic Evaluation from a US Perspective.

Abstract

Background: Recently, the gene therapy eladocagene exuparvovec received accelerated approval from the US Food and Drug Administration (as eladocagene exuparvovec-tneq) for treatment of aromatic L-amino acid decarboxylase deficiency (AADCd), a rare, infantile-onset disorder characterized by developmental delays.

Objectives: To conduct a US, modified societal perspective cost-utility analysis comparing eladocagene exuparvovec versus best supportive care (BSC).

Methods: Multistate survival modeling was implemented tracking disease progression from a "no motor function" health state to achievement of motor-function improvements, measured by: (1) multiples of the meaningful score difference (MSD) of the Peabody Developmental Motor Scales-Second Edition (PDMS-2) total score and (2) motor milestones. Eladocagene exuparvovec trials informed clinical inputs. Health-state utilities were from a US time-trade-off study that valued AADCd quality-of-life impacts. Outcomes were discounted (3%); costs were reported in 2024 US dollars. Scenario analyses, characterizing alternative approaches of the multistate survival model analyses and probabilistic sensitivity analysis to assess the impact of parameter uncertainty, were conducted.

Results: Discounted incremental quality-adjusted life-years (QALYs) for eladocagene exuparvovec were 20.83 (multiples of the MSD of total PDMS-2) and 18.44 (motor milestones). Incremental cost per QALY ranged from $199,007-$224,104. The scenario and sensitivity analyses results supported the validity of the base case analysis.

Conclusions: Eladocagene exuparvovec is associated with considerable QALY gains compared with BSC. Within the context of other ultra-rare and/or one-time treatments, eladocagene exuparvovec provides substantial clinical improvements at lower cost than many other rare-disease treatments. Findings from this study highlight that eladocagene exuparvovec is an important treatment option for patients with AADCd.