PHARMACOECONOMIC ANALYSIS OF CALCIMIMETICS FOR PHARMACOTHERAPY OF SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH HEMODIALYSIS IN UKRAINE Mishchenko O., Mishchenko M., Adonkina V. National University of Pharmacy, Kharkiv, Ukraine Introduction Calcium sensing receptor is an important target for the treatment of Main outcomes and measures. The primary efficacy end point was non- secondary hyperparathyroidism (SHPT). Etelcalcetide hydrochloride is a inferiority of etelcalcetide at achieving more than a 30% reduction from novel peptide calcimimetic agent that has a similar mechanism of action baseline in mean predialysis PTH concentrations during weeks 20-27 (non- as cinacalcet hydrochloride. Clinical trials of etelcalcetide have been inferiority margin, 12.0%). performed in the US, Europe, and Japan, and these trials demonstrated Therefore, taking into account the described results of the comparative the safety and efficacy of etelcalcetide in dialysis patients. The use of clinical study of intravenous calcimimetics etelcalcetide compared with etelcalcetide in Ukraine is complicated due to the high cost of the drug cinacalcet, the parameter of clinical efficacy in the pharmacoeconomic analysis and needs a pharmacoeconomic substantiation. was chosen the proportion of patients who achieved a decrease in PTH level by more than 50%, which is more consistent with the proportion reached the target PTH level of < 300 pg/ml. For etelcalcetide - 52.4%; for cinacalcet - The aim: 40.2%, the difference 12.2% (p=0.001; 4.7% to 19.5%) with the predominance Pharmacoeconomic substantiation of the feasibility of etecalcetide of etelcalcetide. inclusion in the National List of Ukraine as intravenous calcimimetic for The impact of calcimimetics treatment on clinical outcomes such as the treatment of patients with chronic kidney disease (CKD) and SHPT death (all cases), cardiovascular events (CVEs), bone fractures and on hemodialysis. parathyroidectomy (PTx) was modeled to estimate cost as biomarkers in etelcalcetide studies were associated with these clinical events.

Objectives and Methods: Table 1 - Relative risk (RR) of clinical events

Pharmacoeconomic analysis of "cost-effectiveness" of etelcalcetide Clinical RR: Etelcalcetide vs. RR: Cinacalcet vs. in comparison with cinacalcet for pharmacotherapy of secondary events placebo [95% ДІ] placebo [95% ДІ] hyperparathyroidism in patients with chronic kidney disease treated with Cardiovascular events hemodialysis was conducted from the perspective of the national payer. 0,72 [0,59, 0,88] 0,78 [0,67, 0,91] (CVEs) (non-fatal) Research horizon 1 year. The cost of drugs, for the treatment of Bone fractures (non-fatal) 0,67 [0,50, 0,89] 0,73 [0,59, 0,92] cardiovascular events, bone fractures, parathyroidectomy and indirect costs associated with mortality of patients (burial) have been taken into Parathyroidectomy (PTx) 0,17 [0,11, 0,25] 0,25 [0,19, 0,33] account. Costs were expressed in €, taking into account the national Death (all cases) 0,75 [0,62, 0,89] 0,80 [0,69, 0,91] currency rate on March 2019 1 € - 30.46 UAH. В. Stollenwerk et al., 2016 [2]: V. Belozeroff et al., 2015 [3]; Reference The proportion of patients with a decrease in PTH > 50% was used В. Stollenwerk et al. [4] В. Stollenwerk et al. [4] as a measure of clinical efficacy. Dosage of etelcalcetide - 2.5 mg three times a week intravenously at The results of "cost-effectiveness“ analysis are shown in table 2. the end of hemodialysis; dose of cinacalcet - an initial dose of 30 mg per day orally, a median dose of 51.4 mg per day. Table 2 - The results of "cost-effectiveness“ analysis

Results: Cost based on RR of event, € Events Cost, € Etelcalcetide Cinacalcet In the pharmacoeconomic analysis the “decision tree” model with a CVEs 2 729.74 1 965.41 2 129.20 study horizon of 1 year was used (Fig. 1). Bone fractures 497.86 333.57 363.44 Parathyroidectomy 1 076.33 182.98 269.08 Indirect cost associated with 134.60 100.95 107.68 burial Treatment with drugs for year 2962.26 1 521.12 Total cost 5 545.17 4 390.52 Cost difference 1 154.65 Proportion of patients with PTH 52.4 40,2 reduction > 50% The difference in efficacy 12.2 Cost-effectiveness ratio (СER) 10 582.4 10 921.69

The results of the cost-effectiveness analysis indicate that etelcalcetide is more cost-effective: the cost-effectiveness ratio (CER) is € 10582.40 (cost per one patient lowering PTH >50%) compared to € 10921.69 for cinacalcet.

Conclusion:

Etelcalcetide is more effective, and safe as cinacalcet, more beneficial forfor patient and more cost-effective from the perspective of the national payer. Figure 1. The "decision tree" model

Reference: Analysis of the clinical efficacy and safety of etalcalcetide 1. Effect of etelcalcetide vs cinacalcet on serum parathyroi hormone in patients receiving and the drug comparison of cinacalcet hemodialysis with secondary hyperparathyroidism. A randomized clinical trial / Geoffrey A. Block, David A. Bushinsky, Sunfa Cheng, John Cunningham, Bastian Dehmel // JAMA. The indicators of clinical efficacy and safety of the drugs were taken from Original Investigation. 2017. Vol. 317. № 2. Р.157-164. 2. Stollenwerk B., Dehmel B., Akehurst R., Parfrey P., Briggs A., Iannazzo S. et al. Modelling randomized, double-blind, double-dummy active clinical trial was conducted Etelcalcetide effectiveness on health outcomes: Relating biochemical outcomes to mortality, comparing IV etelcalcetide vs oral placebo and oral cinacalcet vs IV placebo cardiovascular event, fractures and parathyroidectomy. 16th Biennial European Conference, in 683 patients receiving hemodialysis with serum parathyroid hormone SMDM. 2016. (PTH) concentrations higher than 500 pg/mL on active therapy at 164 sites in 3. Belozeroff V., Chertow G.M., Graham C.N., Dehmel B., Briggs A.H. Economic evaluation of cinacalcet in the United States: the EVOLVE trial. Value in health : the journal of the the United States, Canada, Europe, Russia, and New Zealand [1]. International Society for Pharmacoeconomics and Outcomes Research. 2015;online first. Interventions: etelcalcetide intravenously and oral placebo (n = 340) or oral 4. A Decision-analytic model to assess the cost-effectiveness cinacalcet and IV placebo (n = 343) for 26 weeks. The IV study drug was of etelcalcetide vs. cinacalcet / В. Stollenwerk, S. Iannazzо, R. Akehurst et al. administered 3 times weekly with hemodialysis; the oral study drug was PharmacoEconomics. https://doi.org/10.1007/s40273-017-0605-2 administered daily.