Cost-Effectiveness Analysis of Velmanase Alfa in Patients with Alpha Mannosidosis from a UK Health Service Perspective

OBJECTIVES: Alpha-mannosidosis (AM) is an ultra-rare lysosomal storage disorder. Oligosaccharide accumulation leads to varied symptoms, including cognitive impairment, skeletal abnormalities, hearing loss, and infections. Velmanase alfa (VA) is the first enzyme replacement therapy approved for AM. In 2023, NICE recommended VA for treating non-neurological symptoms of mild/moderate AM in patients starting treatment <18 years. Building on learnings from NICE, this updated cost-utility analysis for AM incorporated new long-term data from rhLAMAN trials and updated the model structure to better reflect disease progression in AM and the treatment benefits of VA.

METHODS: The Markov model compared VA with best supportive care (BSC) from a UK NHS perspective over a lifetime. Outcomes were quality-adjusted life-years (QALYs) and life-years gained. Based on expert feedback, the model was updated from 5 to 6 health states: infection, death, and 4 mobility states (normal walking; occasional walking aid/wheelchair use; walking aid-dependent; wheelchair-dependent). Within mobility states, patient descriptors of additional AM symptoms that impact resource use and/or quality-of-life were included. Transition probabilities were informed by VA studies up to 12 years, literature, and structured expert elicitation. Adult-onset and child-onset disease were considered separately.

RESULTS: Updated base-case results showed that compared to BSC, VA delayed disease progression to worse mobility states. VA was associated with lower resource use and higher QALYs, but treatment-related costs were higher than BSC. Uncertainties associated with assumptions used to populate late-stage mobility states were explored in scenario analyses. Overall, updated results aligned with the UK NICE conclusions, with VA having a higher likelihood of cost-effectiveness in child-onset disease compared with adult-onset, highlighting the importance of early treatment initiation.

CONCLUSIONS: VA was considered cost-effective by NICE in mild/moderate AM if started <18 years. This updated analysis incorporated long-term data and additional disease descriptors which strengthen the likelihood of cost-effectiveness in all patients with AM.