Cost-Effectiveness of Treatment Strategies for Selumetinib to Neurofibromatosis Type I Inoperable Plexiform Neurofibromas Patients Aged 3 to 18

Abstract

Assessing the cost effectiveness for drugs targeting ultra-rare diseases is complex given the limited clinical evidence for many drugs, yet is growing in importance as the number of these drugs being commercialized is increasing rapidly. Selumetinib is a recently FDA-approved MEK inhibitor for patients aged 3 to 18, with Neurofibromatosis Type I (NF1) Inoperable Plexiform Neurofibromas (PN), a rare genetic disorder, and has been shown in clinical trials to stabilize and contract tumors by up to 20%. As this is an expensive drug with costs ranging from $76,672.03 to $357,802.84CAD (2022) per year of treatment depending on one’s body-surface-area, examining its cost-effectiveness to the health system is important; yet made difficult due to the behaviour of the disease largely dependent on one’s age. Accordingly, this paper uses the best available clinical evidence, including that of the recent SPRINT clinical trial, to produce a time-dependent Markov model, where costs, utilities and probabilities are based on either the Markov stage, patient age, or both; to evaluate the cost-effectiveness of potential dosing strategies of Selumetinib for NF1 Inoperable PN patients aged 3 to 18. Potential treatment strategies were developed, differing on the number of years a patient would take Selumetinib following clinical response. Incremental cost effectiveness ratios (ICER), representing cost per quality adjusted life year (QALY), were calculated for the strategies, which ranged from $74,671.90 CAD to $255,674.71 CAD. A Monte-Carlo simulation was run in each scenario, assuming a maximum willingness-to-pay threshold of $150,000, which revealed Selumetinib being cost-effective in 70.94% of iterations in the lowest intensity strategy, and in only 6.717% of iterations of the highest intensity. Recognizing this study is limited to understanding the cost-effectiveness of potential treatment strategies of this drug for this population, this paper hopes to support development of such strategies, along with clinical and epidemiological evidence, in providing an economic perspective. Beyond this application, this paper sets the stage not only for further cost-effectiveness of Selumetinib for other populations, but also of other novel drugs with costs, utilities, and probabilities, in part, based on patient age, through use of the time-dependent Markov model. Future research directions are discussed, based on the limitations of the current study.