RWD129 Cost Effectiveness of Onasemnogene Abeparvovec in Infants with Presymptomatic Spinal Muscular Atrophy in Italy

Objectives Spinal muscular atrophy (SMA) is a devastating rare disease and the most common genetic cause of infant death. Patients with SMA are lacking survival motor neuron 1 (SMN1) gene, leading to reduced SMN protein, loss of functional motor neurons, and progressive, debilitating and often fatal muscle weakness. Though SMN1-targeting treatments like onasemnogene abeparvovec, a one-time gene therapy infusion, can be costly, they provide significant motor improvements in patients with SMA. We sought to assess the cost effectiveness of treatment with onasemnogene abeparvovec versus other disease-modifying agents in infants with genetically confirmed, presymptomatic SMA. Methods A Markov model based on the Italian NHS perspective and a lifetime time horizon was developed to assess the cost effectiveness of onasemnogene abeparvovec compared with other therapies (nusinersen, risdiplam, and best supportive care [BSC]). Patients were stratified as two-copy and three-copy SMN2 cohorts, and seven health-states were assessed: broad range of normal development, non-sitter, sitter, delayed walker, experiences later onset SMA, non-sitter (permanent assisted ventilation), and death. SPR1NT, NURTURE, and RAINBOWFISH trials were used to estimate treatment effects. Health outcomes were expressed in QALYs. Costs were extrapolated from Italian national tariffs. Deterministic and probabilistic sensitivity analyses were developed to characterize the uncertainty around the models’ parameters. Results In the two-copy cohort, onasemnogene abeparvovec was dominant versus nusinersen and risdiplam and cost-effective versus BSC. In the three-copy cohort, onasemnogene abeparvovec was associated with costs and health outcomes similar to nusinersen, and dominant compared with risdiplam. In the full cohort scenario, onasemnogene abeparvovec was less costly and more effective versus nusinersen and risdiplam. Results of sensitivity analyses demonstrated the robustness of the results. Conclusions Onasemnogene abeparvovec is a cost-effective option for the treatment of infants with genetically confirmed presymptomatic SMA.