Budget Impact of First-Line Bosutinib for Chronic Phase Chronic Myeloid Leukemia on a US Health Plan
Authors: Welch Verna L , Quon Peter , Zou Denise , Uyei Jennifer , Wu Sherry , Xiao Ying , Mamolo Carla M. 
Published: October 2019

Abstract
Introduction: Tyrosine kinase inhibitors (TKIs) have transformed the treatment paradigm for chronic myeloid leukemia (CML). Although not curative, TKIs have increased the life expectancy of patients with CML to approximately that of the general population. There are currently 5 TKIs (imatinib, bosutinib, dasatinib, nilotinib, and ponatinib) approved in the United States to treat CML. Bosutinib was initially approved in September 2012 for the treatment of patients with Philadelphia chromosome-positive (Ph+) CML intolerant or resistant to prior therapy; the indication was expanded in December 2017 to patients with newly diagnosed chronic phase (CP) CML, based on data from the phase 3 BFORE trial demonstrating superior efficacy vs imatinib in this population. A budget impact model was developed to estimate the change in cost to US commercial payers following the addition of first-line (1L) bosutinib to the drug formulary for newly diagnosed Ph+ CP CML. As the introduction of bosutinib in the 1L setting is expected to have a halo effect on treatment pathways and utilization in subsequent treatment lines, the model also captured second- and third-line (2L and 3L) treatments for CML.
Methods: The model estimated the 5-year budget impact of introducing bosutinib for the treatment of newly diagnosed patients with Ph+ CP CML by comparing costs for a hypothetical US health plan with 1 million members in settings with and without 1L bosutinib, and was built with data for TKI costs and medical resource use, including routine follow-ups and management of adverse events (AEs). The model population was comprised of adult patients with Ph+ CP CML without the T315I mutation, which carries a poor prognosis, who were receiving 1L, 2L, or 3L TKI treatment, and was calculated from published incidence and prevalence data. In the setting with 1L bosutinib, the model assumed bosutinib would take shares equally from other TKIs, excluding generic imatinib, for 1L use; for 2L and 3L use, where bosutinib was already indicated, changes in bosutinib shares, due to the halo effect of 1L use, were also taken equally from other TKIs. Costs and medical resource use data were obtained from claims data and public sources, and grade 3/4 AE rates (reported in ≥5% of patients) were obtained from the BFORE trial and package inserts for individual TKIs. Treatment response, based on major molecular response (MMR), was also factored and assumed to impact medical resource use. In each year of the model, it was assumed that patients received a full year of assigned treatment, based on US observational data showing median duration of TKI treatment of >1 year for patients with CML. Scenario analyses were conducted to identify the key drivers of budget impact.
Results: Base-case results of the model indicated that the addition of bosutinib as a 1L treatment option for Ph+ CP CML would result in a total budget increase of 0.77% (from $223,234,271 to $224,943,605; Figure) for a hypothetical health plan over 5 years, which translated to total increases of $1.71 per member and $6,465 per treated member. Increases in total annual costs ($47,100 increment in Year 1 to $762,930 increment in Year 5) were mostly due to 1L drug costs, with low-cost increases per member per year ($0.05 in Year 1 to $0.76 in Year 5) and per member per month (<$0.01 in Year 1 to $0.06 in Year 5). By line of TKI treatment, the total budget change was a 1.05% increase for 1L, a 0.24% increase for 2L, and a 0.05% decrease for 3L (Figure). The overall cost increase was partially offset by reductions in costs related to AE management (−$82,290) and other medical resource use (−$75,608), due to a higher number of patients achieving an MMR. Scenario analyses suggested that the main drivers of budget impact were the time horizon, prevalence of CML, rate of T315I mutation in patients with CML, and uptake of bosutinib as 1L treatment for CP CML.
Conclusions: The introduction of bosutinib as 1L treatment for newly diagnosed patients with Ph+ CP CML resulted in minimal budget impact to a US health plan. 1L drug costs, which accounted for most of the incremental costs, were partially offset by decreases in the costs of AE management and other medical resource use. Increased utilization of bosutinib in the 1L and 2L settings resulted in decreased utilization and reduced total costs in the 3L setting. These data indicate bosutinib may be an important new 1L treatment option for patients with Ph+ CP CML, with low budget impact.

Disclosures
Welch: Pfizer: Employment, Equity Ownership. Quon:Pfizer: Consultancy. Zou:Pfizer: Consultancy. Uyei:Pfizer: Consultancy. Wu:Pfizer: Consultancy. Xiao:Pfizer: Consultancy. Mamolo:Pfizer: Employment, Equity Ownership.