Authors' objectives: The academic technology assessment group (ATAG) reviewed a report on tenapanor's additional benefits and cost-effectiveness for hyperphosphatemia in patients with end-stage kidney disease on dialysis submitted by the manufacturer of tenapanor (Kyowa Kirin). This report summarizes the results of the review and re-analysis by the ATAG. In evaluating the additional benefits of tenapanor, the manufacturer used pill-burden as the outcome for (a) the newly initiating or switching phosphate binder population and effect of lowering serum phosphorus concentration as the outcome for (b) the add-on phosphate binder population. For population (a), the manufacturer explained that tenapanor had the additional benefits over ferric citrate by referring to the 7791-007 trial which showed tenapanor reduced the pill-burden. The ATAG determined that the pill-burden was a process indicator and not appropriate as the outcome to characterize tenapanor in terms of clinical efficacy, safety, and health-related quality of life (HRQOL). The ATAG inquired the manufacturer about the view of the additional benefits when the serum phosphorus concentration was used as an outcome. The manufacturer performed a matching-adjusted indirect comparison (MAIC) with tenapanor for ferric citrate and sucroferric oxyhydroxide, respectively. These comparisons showed a superior tendency of tenapanor compared to iron-based phosphate binders, but no statistical significances were detected. The ATAG pointed out that the clinical trial data of tenapanor which the manufacturer used in the MAIC had a problem regarding the comparability and identified a more appropriate data of tenapanor. When comparing the data of tenapanor with clinical trial data of ferric citrate and sucroferric oxyhydroxide without statistical adjustments, at least no superior tendency of tenapanor was observed. Given this, the ATAG judged that tenapanor had no additional benefits compared with iron-based phosphate binder in population (a). Subsequently, the ATAG performed a cost-minimization analysis. For population (b), the manufacturer performed an evaluation on additional benefits of tenapanor when added to existing phosphate binders by referring to the 7791-005 trial of tenapanor. In that study, tenapanor reduced serum phosphorus concentrations compared to placebo (difference of change in serum phosphorus concentration: -1.76 mg/dL [95% confidence interval: -2.16 to -1.37]). The ATAG accepted this evaluation. Thus, the ATAG judged that tenapanor had the additional benefits when added to existing phosphorus binders. It was therefore appropriate to carry out the costeffectiveness analysis for population (b). The manufacturer's analysis consisted of two phases: a short-term phase and a long-term one. In the short-term phase, a decision-tree model was applied, resulting in four serum phosphate concentration subgroups. In the long-term phase, a Markov model with three heath states characterized by survival, with cardiovascular disease, and death. In both populations, the cost-effectiveness analyses were performed by using quality-adjusted life years (QALYs) as the outcome measure. As discussed above, the ATAG performed the cost-minimization analysis for population (a). Additionally, to account for uncertainty in pill-burden, a cost-effectiveness analysis considering changes in HRQOL due to the number of tablets taken was conducted as a sensitivity analysis. In these analyses, sucroferric oxyhydroxide was used as the comparator. In the base-case analysis for population (a), tenapanor incurred an incremental cost of JPY 144 compared to sucroferric oxyhydroxide. The sensitivity analysis confirmed a high likelihood that the incremental cost-effectiveness ratio (ICER) would exceed 10 million yen per QALY. For population (b), the ATAG accepted the manufacturerfs analysis as appropriate. The ICER of the tenapanor group against the comparator group was the ICER of JPY 3,414,644 per QALY. These results suggest that, from the perspective of public health care payer in Japan, ICERs for tenapanor against comparator technologies are likely to belong to the eequivalent (or inferior) in effectiveness and expensivef interval for population (a) and to emore than JPY 2 million per QALY and less than JPY 5 million per QALYf for population (b).

Project Status: Completed

URL for project: https://c2h.niph.go.jp/en/

Year Published: 2025

URL for published report: https://c2h.niph.go.jp/en/results/C2H2304.html

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: Japan

Organisation Name: Center for Outcomes Research and Economic Evaluation for Health

Contact Address: 2-3-6 Minami, Wako-shi, Saitama 351-0197 Japan

Contact Name: Takeru Shiroiwa

Contact Email: t.shiroiwa@gmail.com