Metachromatic leukodystrophy (MLD) is an ultra-rare neurodegenerative disease which leads to motor and cognitive decline and premature death. The aim of this study was to determine the cost-effectiveness of a definitive ex vivo gene therapy, atidarsagene autotemcel (arsa-cel), compared to best supportive care for the treatment of MLD from the French perspective.

A de novo cost-effectiveness model based on a 7-state partitioned-survival model was developed for pre-symptomatic patients with Late Infantile (LI; predicted age at symptom-onset ≤30 months) and Early Juvenile (EJ; predicted age at symptom-onset 30 months to <7 years) variants. Health states were defined by Gross Motor Function Classification (GMFC-MLD) (LI and EJ) and Development Quotient (DQ) scores (EJ only) at three cognitive levels (normal/mild, moderate, and severe). Health state transitions were based on patient-level data from arsa-cel clinical trials. A lifetime time horizon and collective perspective were used. Resource use and clinical assumptions beyond the trial duration were derived through structured expert elicitation. Costs were from a variety of sources including the French national databases on Hospital costs (PMSI), Biological Procedures (NABM) and official tariffs for medical visits (AMELI). Utilities to derive quality of life of the health states were from a vignette study based on time trade-off valuations of health state descriptions. Caregiver utilities were based on EQ5D-5L from an international caregiver survey including French respondents. Model validation was conducted with extensive scenario and sensitivity analyses.

For the combined MLD population (comprising LI and EJ), base case analysis indicated that arsa-cel is associated with incremental gains in excess of 28 QALYs (discount rate of 2.5% for first 30 years then 1.5%).

There are no official cost-effectiveness thresholds in France. However, the study shows that arsa-cel has comparable or better cost-effectiveness estimates than other drugs for rare diseases that are currently funded by the French health system.