Zanubrutinib Not Cost-Effective in China Against Fixed-Duration R-Bendamustine in 1L CLL

Treatment with zanubrutinib not cost-effective compared with a commonly used, fixed-duration option for treatment-naive chronic lymphocytic leukemia (CLL), according to findings of a cost-effectiveness study conducted from the Chinese health care system perspective.

The study, published in Clinical Therapeutics, found that the price tag for the second-generation Bruton tyrosine kinase inhibitor (BTKi) would need to be reduced by 30% in order to be cost-effective compared with bendamustine-rituximab (R-bendamustine) for these patients.¹

The analysis compared the cost-effectiveness of zanubrutinib vs bendamustine-rituximab for first-line treatment of CLL from the perspective of the Chinese health care system. | Image Credit: © pla2na - stock.adobe.com

“Bruton’s tyrosine kinase inhibitors represent a milestone in the treatment of CLL,” the authors wrote. ”The cost-effectiveness of such new treatments can vary significantly across different health care systems, influenced by factors like government-regulated drug pricing and market-determined pricing in different countries. Additionally, the allocation of medical resources, insurance systems, and reimbursement policies for innovative drugs in various nations plays a crucial role in the cost-benefit analysis of these treatments.”

Compared with R-bendamustine, zanubrutinib significantly improved progression-free survival in the phase 3 SEQUOIA trial of previously untreated patients with CLL or small lymphocytic leukemia (HR, 0.42; 95% CI, 0.28-0.63; 2-sided P < .0001). Zanubrutinib also showed an acceptable safety profile, consistent with previous studies of the treatment.²

However, these clinical improvements do not warrant the price of zanubrutinib, which requires continuous administration until disease progression or unacceptable toxicity, suggests the cost-effectiveness analysis.¹ By comparison, R-bendamustine is given for 6 cycles.

Patient characteristics from the SEQUOIA trial were used for the hypothetical patient population in this analysis: patients aged 65 years or older, or 18 years or older with comorbidities; an Eastern Cooperative Oncology Group score of 0 to 2; and adequate hepatic, renal, and hematological function.

Total costs for zanubrutinib reached more than $98,000 compared with $53,000 for R-bendamustine. The analysis showed that zanubrutinib costs an additional $58,000 per quality-adjusted life-year (QALY) gained. When threshold was reduced to approximately $38,000, there was a 3.70% probability of being cost-effective. Based on data showing survival of over 10 years from the time of CLL diagnosis, the researchers used a 10-year time span for their analysis. Expanding the time span to 20 years resulted in a slight reduction, though no significant differences were observed.

One-way sensitivity analysis showed that progressed disease was the most consequential parameter contributing to the incremental cost-effectiveness ratio (ICER) of zanubrutinib in contrast to R-bendamustine, though the general results remained unchanged when adjusting the utility of PD.

“The cost of zanubrutinib was also to be the main influencing factor of economic results,” noted the researchers. “As a crucial pharmacological intervention for patients with CLL, the cost of zanubrutinib plays a significant role in determining the overall treatment expenses incurred by individuals undergoing CLL therapy. A higher discount rate results in a diminished present value of forthcoming costs and effects, whereas a lower discount rate elevates their present value. Consequently, the utilization of varying discount rates can lead to divergent evaluation outcomes of the ICER, thereby influencing the judgment of decision-makers regarding the economic advantages of treatment strategies. However, in this study, discount rates impact little.”

While the current study showed an unlikelihood of cost-effectiveness of zanubrutinib in the first-line setting against R-bendamustine, previous cost-effectiveness analyses have suggested that, in the relapsed and refractory setting, zanubrutinib may be more cost effective compared with another BTKi. Over a similar 10-year period, with a threshold of $150,000 per QALY, zanubrutinib showed an ICER of approximately $120,000 per QALY gained compared with ibrutinib.³

References:

1. Nie J, Mu L, Wu H, Yuan S, Tang K, Wu J. Cost-effectiveness of zanubrutinib versus bendamustine and rituximab in patients with untreated chronic lymphocytic leukemia. Clin Ther. Published online September 16, 2024. doi:10.1016/j.clinthera.2024.08.016
2. Tam CS, Brown JR, Kahl BS, et al. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Lancet Oncol. 2022;23(8):1031-1043. doi:10.1016/S1470-2045(22)00293-5
3. Kang D-W, Wang L, Short NJ, et al. Cost effectiveness of zanubrutinib versus ibrutinib in relapsed or refractory chronic lymphocytic leukemia. Pharmacoeconomics. 2024;42(4):409-418. doi:10.1007/s40273-023-01346-8