Early Cost-Effectiveness of Onasemnogene Abeparvovec-xioi (Zolgensma) and Nusinersen (Spinraza) Treatment for Spinal Muscular Atrophy I in The Netherlands With Relapse Scenarios

• Published in: Value in health 2021-06, Vol.24 (6), p.759-769
• Main Authors: Broekhoff, Thomas F., Sweegers, Carly C.G., Krijkamp, Eline M., Mantel-Teeuwisse, Aukje K., Leufkens, Hubert G.M., Goettsch, Wim G., Vreman, Rick A.
• Format: Article
• Language: English
• Subjects: advanced therapy medicinal product; AVXS-101; Biological Products - adverse effects; Biological Products - economics; Biological Products - therapeutic use; Clinical Trials as Topic; Comparative Effectiveness Research; Cost analysis; Cost-Benefit Analysis; cost-effectiveness; Decision makers; Drug Costs; Female; Gene therapy; Genetic Therapy - adverse effects; Genetic Therapy - economics; Health Status; health technology assessment; Humans; Infant; Male; Mathematical models; microsimulation; Models, Economic; Multiplication; Netherlands; Neuromuscular diseases; Oligonucleotides - adverse effects; Oligonucleotides - economics; Oligonucleotides - therapeutic use; Quality adjusted life years; Recombinant Fusion Proteins - adverse effects; Recombinant Fusion Proteins - economics; Recombinant Fusion Proteins - therapeutic use; Recurrence; Relapse; Sensitivity analysis; Spinal Muscular Atrophies of Childhood - diagnosis; Spinal Muscular Atrophies of Childhood - economics; Spinal Muscular Atrophies of Childhood - genetics; Spinal Muscular Atrophies of Childhood - therapy; Spinal muscular atrophy; Technology Assessment, Biomedical; Time Factors; Treatment Outcome; Uncertainty; Ventilation; Willingness to pay; Zolgensma
• ISSN: 1098-3015; 1524-4733
• DOI: 10.1016/j.jval.2020.09.021

Onasemnogene Abeparvovec-xioi (AVXS-101) is a gene therapy intended for curative treatment of spinal muscular atrophy (SMA) with an expected price of around €2 000 000. The goal of this study is to perform a cost-effectiveness analysis of treatment of SMA I patients with AVXS-101 in The Netherlands including relapse scenarios. An individual-based state-transition model was used to model treatment effect and survival of SMA I patients treated with AVXS-101, nusinersen and best supportive care (BSC). The model included five health states: three health states according to SMA types, one for permanent ventilation and one for death. Deterministic and probabilistic sensitivity analyses were performed. Effects of relapsing to lower health states in the years following treatment was explored. The base-case incremental cost-effectiveness ratio (ICER) for AVXS-101 versus BSC is €138 875/QALY, and €53 447/QALY for AVXS-101 versus nusinersen. If patients relapse within 10 years after treatment with AVXS-101, the ICER can increase up to 6-fold, with effects diminishing thereafter. Only relapses occurring later than 50 years after treatment have a negligible effect on the ICER. To comply with Dutch willingness-to-pay reference values, the price of AVXS-101 must decrease to €680 000. Based on this model, treatment with AVXS-101 is unlikely to be cost-effective under Dutch willingness-to-pay reference values. Uncertainty regarding the long-term curative properties of AVXS-101 can result in multiplication of the ICER. Decision-makers are advised to appropriately balance these uncertainties against the price they are willing to pay now.