OBJECTIVES: MLD is an ultra-rare, rapidly progressive neurodegenerative disease which leads to motor and cognitive decline and premature death. The aim of this study was to determine the cost-effectiveness of an autologous ex vivo gene therapy, arsa-cel, compared to standard of care for the treatment of early-onset MLD from the Spanish National Health System (MHS) and societal perspective.

METHODS: A cost-effectiveness model was developed based on a partitioned-survival framework and Markov structure to model disease progression in MLD using the seven stage Gross Motor Function MLD scale (GMFC-MLD) in patients with Late Infantile (LI; age at symptom-onset ≤30 months) and Early Juvenile (EJ; age at symptom-onset 30 months to <7 years) MLD. Health state transitions were based on patient-level data from arsa-cel clinical trials. A lifetime time horizon was adopted; costs and outcomes were discounted at 3% per annum. Healthcare resource use consumption and unit cost data from EsSalud were used to calculate costs by GMFC-MLD health state. Utilities were derived from a UK vignette study based on time trade-off valuations of health state descriptions and an algorithm involving the Spanish EQ-5D tariff to reflect the preferences of the Spanish general population. Caregiver utilities and societal inputs were calculated from an international caregiver study and median annual earnings in Spain.

RESULTS: For the combined MLD population (pre-symptomatic LI and EJ, and early symptomatic EJ), the base case analysis indicated that arsa-cel is associated with discounted incremental gains vs. BSC of 20.76 QALYs. Based on the list price of arsa-cel, the incremental cost-effectiveness ratio for the combined MLD population treated with arsa-cel vs. standard of care was €128,387/QALY gained and €106,522/QALY gained from a payer and societal perspective, respectively. Sub-group analyses indicate that arsa-cel is most cost-effective in patients treated pre-symptomatically.

CONCLUSIONS: Arsa-cel has shown to be cost-effective for the Spanish NHS versus BSC.