Cost-effectiveness of Voretigene Neparvovec-rzyl vs Standard Care forRPE65-Mediated Inherited Retinal Disease

Abstract

IMPORTANCE Voretigene neparvovec-rzyl, the first gene therapy approved by the US Food and Drug Administration, was approved for the treatment for RPE65-mediated inherited retinal disease (IRD) in December 2017. This gene therapy is associated with high up-front costs and high efficacy, although of unknown duration, and its cost-effectiveness has not been assessed with RPE65 IRD-specific, longitudinal, patient-observation-level data. OBJECTIVE To assess the incremental cost-effectiveness ratio (ICER) of voretigene neparvovec-rzyl compared with standard care for RPE65-mediated inherited retinal disease. DESIGN, SETTING, AND PARTICIPANTS In this economic analysis, a health state transition model based on visual acuity and field with a lifetime horizon was developed to estimate the cost-effectiveness of voretigene neparvovec-rzyl. The model was populated with data from a clinical trial of voretigene neparvovec-rzyl to evaluate treatment outcome and a natural history study of RPE65-mediated IRD to examine disease progression. Direct costs were derived from the literature. Indirect costs, including educational attainment, productivity, caregiver burden, and governmental programs, were estimated using published literature and data analysis of public national surveys. A health utility vignette study specific to RPE65-mediated IRD was used for health utility inputs. The cost-effectiveness study described in this article was conducted from September 15, 2017, to August 23, 2018. EXPOSURES Bilateral voretigene neparvovec-rzyl therapy or standard care. MAIN OUTCOMES AND MEASURES Incremental cost-effectiveness ratio. RESULTS The model population included 70 patients with RPE65-mediated IRD, with a mean age of 15 years; 42 of 70 patients (60%) were female. In the base case, voretigene neparvovec-rzyl compared with standard care was associated with lower total costs ($2.2 million vs $2.8 million) and higher quality-adjusted life-years (18.1 vs 8.6). Voretigene neparvovec-rzyl remains cost-effective if at least 8.8% of the long-term treatment effect continues after year 3 when including indirect costs and 43.3% when excluding indirect costs, assuming a cost threshold of $150 000 per quality-adjusted life-year. CONCLUSIONS AND RELEVANCE Results of this study suggest that voretigene neparvovec-rzyl is cost-effective compared with standard care when using a lifetime horizon, excluding indirect costs, and using a threshold of $150 000 per quality-adjusted life-year.

An Economic Evaluation of Voretigene Neparvovec for the Treatment of Biallelic RPE65-Mediated Inherited Retinal Dystrophies in the UK

“…Cost-effectiveness analyses have also been performed by the Institute for Clinical and Economic Review (Zimmermann et al [39]) and by Johnson et al [42], both conducted from a US perspective. The key differences among the three analyses are the duration of treatment effect, the health state utility values and the approach to modelling long-term changes in VA and VF.…”

The Evolution of Retinal Gene Therapy: From Clinical Trials to Clinical Practice

“…3,4 However, such cost-valuation models can be influenced by the assumptions made at baseline, and other analyses have shown Luxturna to be cost effective in a number of scenarios and with a number of sensitivities. 5,6 A further question is: how should we be measuring functional improvement after approval? The primary outcome measure in the phase 3 trial was the multiluminance mobility test developed by Spark Therapeutics.…”

Cost Effectiveness of Voretigene Neparvovec for RPE65-Mediated Inherited Retinal Degeneration in Germany

“…We built a probabilistic lifetime model that simulates pathways of treatment-naïve patients with confirmed biallelic RPE65-mediated IRD. Consistent with previously published economic models for RPE65, we simulate 70 patients 10 in 1000 Monte Carlo simulations, 10,11 where parameters are varied by random draws according to their distribution. Patients are equally divided into two groups and chosen by random draws to be treated with VN or with standard of care (SoC).…”

“…Implementation of the phase III clinical trials' population to an RPE65 simulation model was already successfully performed in similar economic models. 10,11,14 In RPE65-mediated IRD, BCVA, which is often already significantly decreased, is typically relatively stable during the first life decade with a gradual decline starting around life year 15 to 20. 4 To reflect this natural disease progression, our model assumes a constant BCVA until life year 15 to 20.…”

“…In clinical studies, treatment effects manifested within the first month after application and the effect duration was shown to be constant for 4 years after VN administration. 9,15 Our base case scenario assumes that treatment effect is maintained over lifetime, as assumed by Johnson et al 10 The sensitivity analysis simulates a treatment effect duration of 10 years to account for uncertainty with regard to the duration of the treatment effect, because no long-term data are available yet. After this period, the effect wanes with an exponential decrease for another 10 years to the level it would have under SoC treatment.…”