Zanubrutinib Cost-effective and Cost Saving vs Ibrutinib in Waldenström Macroglobulinemia

Posters presented at the AMCP Nexus 2021 meeting reviewed the cost-effectiveness and cost per response for zanubrutinib vs ibrutinib.

In patients with relapsed/refractory Waldenström macroglobulinemia (WM), zanubrutinib is more cost-effective and is cost saving compared with ibrutinib, according to 2 posters presented at AMCP Nexus 2021.

Both therapies are Bruton tyrosine kinase (BTK) inhibitors, although zanubrutinib is a novel highly selective BTK inhibitor and ibrutinib is a first-generation BTK inhibitor. As a next-generation BTK inhibitor, zanubrutinib reduces toxicity while improving outcomes, explained Peter Hillmen, PhD, MB ChB, professor at the University of Leeds and honorary consultant hematologist at Leeds Teaching Hospitals NHS Trust, when he presented results of zanubrutinib at the European Hematology Association 2021 Virtual Congress in June.

One poster at AMCP Nexus 2021 used a partitioned survival model to estimate life-years (LYs), quality-adjusted life-years (QALYs), and costs for zanubrutinib and ibrutinib over a 30-year lifetime horizon.1 Costs included drug and adverse event management for the therapies, as well as routine care and terminal care.

Over a 30-year time horizon, zanubrutinib led to 0.94 LY and 0.84 QALY gained. The total cost of care for zanubrutinib was $11,132, which was primarily driven by patients staying on the therapy longer. The costs driven by longer time to treatment failure were offset partially by other lower costs from zanubrutinib, such as lower monthly drug acquisition and reduced costs of routine and terminal care.

The incremental cost-effectiveness ratio of zanubrutinib was $13,205 per QALY gained.

“Zanubrutinib appears to be cost-effective compared with ibrutinib for the treatment of patients with WM in the US,” the authors concluded.

The second paper estimated the cost per response (CPR) for zanubrutinib vs ibrutinib over a 1-year time horizon using an Excel-based model.2 Clinical response was based on the very good partial response rate from the ASPEN trial, a phase 3 study that compared efficacy and safety of zanubrutinib with ibrutinib. Probabilities for grade ≥ 3 adverse events (AEs) were taken from the ASPEN trial and included in the model, and the assumed treatment duration in the model was 12 months for both arms.

Among modeled patients, the total direct medical cost per patient was $167,924 for patients on ibrutinib vs $152,348 for patients on zanubrutinib. As part of the total cost, the researchers found:

  • CPR for zanubrutinib was $544,100 vs $883,808 for ibrutinib
  • AE costs for zanubrutinib were $4271 vs $4159 for ibrutinib
  • Drug acquisition costs for zanubrutinib were $148,077 vs $163,765 for ibrutinib

They noted that the 30-day wholesale acquisition cost of ibrutinib would need to be reduced by 39% to bring the CPR difference to $0.

“In adult patients with treatment-naïve or relapsed/refractory WM, zanubrutinib represents a cost-saving option to achieve clinical response, with a lower cost per response compared to ibrutinib from a payer perspective in the United States,” the authors concluded.

The FDA approved zanubrutinib for the treatment of adults with WM on September 1, 2021. The approval was based on the results from the ASPEN trial.

At the time, Steven Treon, MD, PhD, director of the Bing Center for Waldenström’s Macroglobulinemia Research at the Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said, “The approval of Brukinsa provides an important new option for targeted therapy in Waldenström’s macroglobulinemia.”


1. Liu R, Castillo J, Tang B, et al. Cost-effectiveness of zanubrutinib versus ibrutinib in adult patients with Waldenström macroglobulinemia in the United States. Presented at: AMCP Nexus 2021; Denver, CO; October 18-21, 2021. Abstract C36.

2. Carter J, Pham H, Balk M, et al. Zanubrutinib versus ibrutinib to treat adults with Waldenström macroglobulinemia: a cost per response model from a payer perspective in the United States. Presented at: AMCP Nexus 2021; Denver, CO; October 18-21, 2021. Abstract C52.

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