Cost effectiveness of nusinersen for patients with infantile-onset spinal muscular atrophy in US

Praveen Thokala,Matt Stevenson,Varun M Kumar,Shijie Ren,Richard H Chapman,Alexandra G Ellis

doi:10.1186/s12962-020-00234-8

Abstract

BackgroundPatients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life expectancy in the absence of treatment. Nusinersen is a disease-modifying therapy for patients with SMA.ObjectiveThe aim of this study was to estimate the cost-effectiveness of nusinersen compared to best supportive care (BSC) in patients diagnosed with infantile-onset SMA in the US.MethodsA de novo economic model was developed with the following health states: “permanent ventilation”, “not sitting”, “sitting”, “walking”, and “death”. Short-term data were sourced from the pivotal clinical trials and studies of nusinersen (ENDEAR and SHINE). Motor function milestones achieved at the end of follow-up in the clinical trials were assumed to be sustained until death. Mortality risks were based on survival modelling of relevant published Kaplan–Meier data. Costs, life years (LYs), and quality-adjusted life years (QALYs) were discounted at 3% per annum, and the analyses were performed from a US health care sector perspective. Scenario analyses and sensitivity analyses were conducted to assess the robustness of the results to key parameters.ResultsIn our base-case analysis, nusinersen treatment achieves greater QALYs and more LYs (3.24 and 7.64, respectively) compared with BSC (0.46 QALYs and 2.40 LYs, respectively), resulting in an incremental cost per QALY gained of approximately $1,112,000 and an incremental cost per LY gained of $590,000 for nusinersen compared to BSC. The incremental cost effectiveness ratios did not fall below $990,000 per QALY gained in scenario and sensitivity analyses. Results were most sensitive to the length of survival, background health care costs, and utility in the “not sitting” and “sitting” health states.ConclusionsThe estimated incremental cost-effectiveness of nusinersen from a US health care sector perspective exceeded traditional cost-effectiveness thresholds. Cost-effectiveness was dependent on assumptions made regarding survival, costs, utilities, and whether the motor function milestones were sustained over lifetime. Given the relatively short-term effectiveness data available for the treatment, a registry to collect long-term data of infantile-onset SMA patients is recommended.

Highlights

Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones and have short life expectancy in the absence of treatment
Cost-effectiveness was dependent on assumptions made regarding survival, costs, utilities, and whether the motor function milestones were sustained over lifetime
Base‐case results The breakdown of quality-adjusted life years (QALYs), life years (LYs) and costs according to health state for the different strategies are presented in Additional file 1

Summary

Introduction

Patients with infantile-onset spinal muscular atrophy (SMA), a rare, genetic neuromuscular disease, do not achieve key motor function milestones (e.g., sitting) and have short life expectancy in the absence of treatment. Nusinersen is a disease-modifying therapy for patients with SMA. Patients with infantile-onset SMA do not achieve key motor function milestones (e.g., sitting) and have short life-expectancy in the absence of treatment. Life expectancy in these infantile-onset SMA patients was less than 2 years and many infants eventually require permanent ventilation. In December 2016, the Food and Drug Administration (FDA) approved nusinersen (Spinraza®, Biogen Idec), a disease-modifying therapy, for the treatment of SMA. There are two clinical trials of nusinersen in infantileonset SMA, including a phase II, open-label, dose-escalation study (CS3A) [8] and a randomized controlled trial with sham control (ENDEAR). Longer-term results are available for infants in ENDEAR who enrolled in the single-arm open label extension (OLE) study SHINE. [15]

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