OBJECTIVES: MLD is an ultra-rare, inherited, multi-systemic disease, with aggressive forms manifesting early in late-infantile and early juvenile stages, which lead to rapid physical and cognitive decline, resulting in significant loss of quality of life (QoL) and premature death. Currently, no approved treatment exists for early-onset MLD. Consequently, the standard of care consists primarily of the best supportive care in Ireland, Belgium, and the Netherlands. This study evaluates the cost-effectiveness of arsa-cel, a one-time gene therapy, compared to BSC.

METHODS: The cost-effectiveness analysis employs a seven-state partitioned survival model, with a monthly cycle length and lifetime horizon, conducted from a healthcare payer perspective for Ireland and Belgium and a societal perspective for the Netherlands. Transition probabilities were informed by clinical trial data, published literature, national registry data, and expert opinions. Discount rates and costs specific to each country were applied in the analysis. Utilities were derived from a study using vignette and time trade-off methods and were subsequently rescaled to align with national tariff standards to reflect the preferences of each country.

RESULTS: For the combined MLD population, the base case ICERs for arsa-cel versus BSC were €146,642 in Ireland, €118,234 in Belgium, and €107,777 in the Netherlands, with incremental QALY gains of 15.5, 25.5, and 24.6, respectively. In a scenario analysis that included a societal perspective (including lost family income, out-of-pocket costs, and productivity gains using the Human Capital Approach), newborn screening, and caregiver disutility, the ICERs for arsa-cel versus BSC were €45,574 for Ireland, €40,374 for Belgium, and €38,803 for the Netherlands.

CONCLUSIONS: Findings suggest arsa-cel yields lifelong QoL improvements, with variable cost-effectiveness among countries due to differing modelling requirements and inputs. Scenario analyses reveal that including broader considerations, such as the societal perspective, newborn screening, and impact on caregivers, considerably lowers all the ICERs, underscoring arsa-cel's value.