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 long-term cost-effectiveness of a recently approved ex vivo gene therapy (OTL-200) compared to best supportive care for the treatment of MLD, using the UK NHS as the base setting.

A de novo cost-effectiveness model based on a 7-state partitioned framework was developed for patients with Late Infantile (LI; age at symptom onset ≤30 months) and Early Juvenile (EJ; age at symptom onset 30 months to 6 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 OTL-200 clinical trials, and expert opinion. Resource use and clinical assumptions beyond the trial duration were derived through structured expert elicitation. Costs were from a variety of sources including NHS reference costs. Utilities were from a vignette study based on TTO valuations of health state descriptions by members of the UK general public (n=101). Caregiver utilities were based on EQ5D-5L from an international survey. Model validation was conducted with extensive scenario and sensitivity analyses.

For the combined MLD population (comprising all variants), base case analysis indicated that OTL-200 is associated with incremental gains in excess of 30 (at a discount rate of 1.5%). The corresponding ICER was below £100,000 per QALY gained. Subgroup analyses indicated OTL-200 was more cost-effective for patients treated pre-symptomatically.

This is the first de novo cost-effectiveness study which has considered both the motor and cognitive aspects of MLD and generated ICERs which are substantially lower than the cost-effectiveness thresholds used in a number of jurisdictions, indicating that OTL-200 is a cost-effective use of resources.