Cost-Effectiveness of Elbasvir/Grazoprevir (EBR/GZR) for Treatment-Naïve (TN) Patients With Chronic Hepatitis C Virus (HCV) Genotype 1b (GT1b) Infection in Russia Shelby Corman, PharmD, MS, BCPS1; Amy Puenpatom, PhD2; Roza Yagudina, PhD3; Andrey Kulikov, PhD3 VIENNA, AUSTRIA; 10-14 APRIL 2019 1Pharmerit International, Bethesda, MD, USA; 2Merck & Co., Inc., Kenilworth, NJ, USA; 3Sechenov University, Moscow, Russia FRI-228 BACKGROUND Table 1: Treatment Inputs RESULTS Figure 2: Cost-Effectiveness Acceptability Curves for Non-cirrhotic Cirrhotic EBR/GZR±RBV and Comparators • An estimated 4.1% of the population in Russia is infected with HCV, of which Duration SVR Duration SVR Base Case Analysis GT1b is the most common1 Treatment Regimen (weeks) (95% CI) (weeks) (95% CI) References GT1b, Treatment-naïve, Non-cirrhotic • EBR/GZR is less costly and more effective (economically dominant) 1.0 8 (F0-2) 0.982 (0.903-1.000) • EBR/GZR is a direct-acting antiviral (DAA) indicated for the treatment of GT1b EBR/GZR 12 1.000 (0.936-1.000) 2-4 over all comparators in cirrhotic patients (Table 5) in Russia2 12 (F3) 0.979 (0.927-1.000) 0.9 EBR/GZR 8 (F0-2) 0.982 (0.960-1.000) • In non-cirrhotic patients, EBR/GZR was cost-saving vs all comparators 0.8 at: presented Poster • As new DAAs are introduced into the market, cost-effectiveness analyses are 3D 12 1.000 (0.940-1.000) 5-7 SIM+PegIFN+RBV 12 (F3) 0.990 (0.966-0.999) and economically dominant over all comparators except OMB/PAR/ 0.7 needed in order to identify the most efficient use of resources SOF+SIM GLE/PIB 8 0.991 (0.897-1.000) 12 1.000 (0.891-1.000) 8-9 RIT+DAS and GLE/PIB, for which QALY differences were negligible effective - 0.6 SOF+SIM 12 0.974 (0.865-0.999) 12* 0.909 (0.587-0.998) 10-11 OMB/PAR/RIT+DAS 0.5 NAR+RIT+PegIFN+RBV 12 0.891 (0.836-0.932) N/A N/A 12 GLE/PIB 0.4 NAR+RIT+PegIFN+RBV SIM+PegIFN+RBV 24* 0.854 (0.806-0.894) 48* 0.854 (0.806-0.894) 13 Table 5: Base Case Results OBJECTIVE 0.3 SOF+DAC 12 1.000 (0.914-1.000) 12+RBV 1.000 (0.701-1.000) 14 Total Total ICUR, EBR/GZR DAC+ASN 24 0.906 (0.805- 1.000) 24 0.893 (0.858-0.929) 15 Discounted Discounted Incremental Incremental vs Comparator 0.2 To compare the cost-effectiveness of EBR/GZR to regimens currently used in Proportion Cost Treatment Regimen Costs (RUB) QALYs Costs QALYs (RUB/QALY) 0.1 Russia for the treatment of TN patients with GT1b HCV infection. *Regimens consist of 12 weeks of simeprevir followed by an additional 12 or 36 weeks of PegIFN + RBV. Abbreviations: 3D, ombitasvir/paritaprevir/ritonavir + dasabuvir; 95%CI, 95% confidence interval; ASN, asunaprevir; Non-cirrhotic (F0-3) 0.0 DAC, daclatasvir; EBR, elbasvir, GLE, glecaprevir; GZR, grazoprevir; NAR, narlaprevir; PegIFN, pegylated interferon; 0 500 1,000 1,500 2,000 2,500 PIB, pibrentasvir; RBV, ribavirin; RIT, ritonavir; SIM, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response EBR/GZR 392,220 11.9494 – – – Cost-effectiveness Threshold (thousands) METHODS SIM+PegIFN+RBV 1,078,505 11.6691 -686,285 0.2804 Dominant Table 2: Weekly Costs, Antiviral Therapy 1.0 GT1b, Treatment-naïve, Cirrhotic DAC+ASN 619,030 11.6732 -226,809 0.2762 Dominant • A Markov model was constructed to evaluate the cost-effectiveness of EBR/GZR Lower Limit Upper Limit 0.9 compared to other DAA regimens over a lifetime time horizon Regimen Base Case (RUB) (–25%) (+25%) OMB/PAR/RIT+DAS 487,042 11.9505 -94,822 -0.0011 Cost saving 0.8 ® • The target population was patients infected with CHC GT1b, stratified by Elbasvir/grazoprevir (ZEPATIER ) 42,502.95 31,877.21 53,128.69 0.7 GLE/PIB 693,651 11.9653 -301,431 -0.0158 DOI: 10.3252/pso.eu.ILC2019.2019 ® Cost saving effective presence of cirrhosis Sofosbuvir (SOVALDI ) 38,754.29 29,065.72 48,442.87 - 0.6 Pegylated interferon 8,397.61 6,298.21 10,497.01 NAR+RIT+PegIFN+RBV 803,808 11.7130 -411,588 0.2364 Dominant • The model consists of 16 health states comprising fibrosis stages, treatment 0.5 Ribavirin 2,418.28 1,813.71 3,022.85 success or failure, decompensated cirrhosis, hepatocellular carcinoma, liver SOF+DAC 747,917 11.9312 -355,697 0.0182 Dominant 0.4 Ombitasvir/paritaprevir/ritonavir + transplant, and liver-related death (Figure 1) 53,801.25 40,350.94 67,251.56 dasabuvir (VIEKIRA PAK®) SOF+SIM 1,266,417 11.9006 -874,197 0.0489 Dominant 0.3 Glecaprevir/pibrentasvir (MAVIRET™) 82,500.00 61,875.00 103,125.00 0.2 Cirrhotic (F4) Proportion Cost Figure 1: State Transition Model for Chronic HCV and Liver Disease Model Narlaprevir (ARLANZA®) 30,142.23 22,606.67 37,677.78 0.1 Ritonavir 392.70 294.53 490.88 EBR/GZR 789,288 11.0885 – – – 0.0 ® Simeprevir (SOVRIAD ) 63,795.41 47,846.56 79,744.26 SIM+PegIFN+RBV 1,595,848 10.4310 -806,560 0.6575 Dominant 0 500 1,000 1,500 2,000 2,500 Daclatasvir (DACLINZA®) 20,898.61 15,673.96 26,123.27 Cost-effectiveness Threshold (thousands) DAC+ASN 853,733 10.6546 -64,445 0.4339 Dominant OMB/PAR/RIT+DAS 895,848 11.0885 -106,560 0.0000 Dominant Table 3: Annual Health State Cost Inputs GLE/PIB 1,240,233 11.0885 -450,945 0.0000 Dominant Lower Limit Upper Limit Base Case (RUB) (–25%) (+25%) SOF+DAC 995,087 11.0885 -205,799 0.0000 Dominant SVR, F0-3 1,533 1,150 1,916 SOF+SIM 1,518,737 10.7847 -729,449 0.3038 Dominant DC,SVR, decompensated F4 cirrhosis; HCC, hepatocellular carcinoma; SVR,19,638 sustained virologic response14,729 24,548 CONCLUSION F0-F3 3,427 2,570 4,284 F4 (compensated cirrhosis) 43,172 32,379 53,965 EBR/GZR is economically dominant over other DAA regimens DC 111,499 83,624 139,374 Deterministic Sensitivity Analyses in cirrhotic patients and is economically dominant or cost-saving HCC, first year 154,930 116,198 193,663 • In one-way sensitivity analyses, SVR rates in patients receiving HCC, subsequent years 36,191 27,143 45,239 EBR/GZR most commonly impacted model conclusions Liver transplant (first year) 1,117,900 838,425 1,397,375 • Lower bound of SVR range Liver transplant (subsequent years) 593,759 445,319 742,199 Hepatic fibrosis stage was based on Metavir fibrosis scoring system: F0 = no fibrosis; F1 = portal fibrosis without septa; F2 = portal fibrosis – Non-cirrhotic patients: EBR/GZR was no longer dominant over REFERENCES: with few septa; F3 = portal fibrosis with numerous septa without cirrhosis; and F4 = compensated cirrhosis; DC = decompensated cirrhosis; Annual discount rate of future cost 5% 0% 5% SOF+DAC or SOF+SIM, with ICURs of RUB 4,703,630 /QALY 1. Gower E, Estes C, Blach S, et al. J Hepatol 2014;61:S45-57. HCC = hepatocellular carcinoma; PDC = one-year post decompensated cirrhosis; PHCC = one-year post hepatocellular carcinoma; DC, decompensated cirrhosis; HCC, hepatocellular carcinoma; SVR, sustained virologic response SVR12 = sustained virologic response 12 weeks after cessation of treatment and RUB 19,155,111 /QALY, respectively 2. Serfaty L, Zeuzem S, Vierling JM, et al. Hepatology 2015;62(Suppl 1): 555A-556A. 3. Zeuzem S, Ghalib R, Reddy KR, et al. Ann Intern Med 2015; 163(1):1-13. – Cirrhotic patients: EBR/GZR was no longer dominant over 4. Jacobson IM, Lawitz E, Kwo PY, et al. Gastroenterology. 2017;152(6):1372-1382.e1372. 16-18 Model Inputs Table 4: Utility Inputs OMB/PAR/RIT+DAS (ICUR, RUB 500,235/QALY), GLE/PIB 5. Welzel TM, Asselah T, Dumas EO, et al. Lancet Gastroenterol Hepatol. 2017;2(7):494-500. • The proportions of patients achieving sustained virologic response (SVR) were 6. Feld JJ, Moreno C, Trinh R, et al. J Hepatol. 2016;64(2):301-307. Lower Limit Upper Limit (RUB 2,116,920/QALY), and SOF+DAC (RUB 966,106/QALY) 7. Ferenci P, Bernstein D, Lalezari J, et al. N Engl J Med 2014;370:1983-1992. obtained from clinical trials (Table 1) Input Base Case (–5%) (+5%) • Upper bound of the SVR range 8. Zeuzem S, Foster GR, Wang S, et al. N Engl J Med. 2018;378(4):354-369. • Medication (Table 2) and annual health state costs (Table 3) were obtained from Disutility, PegIFN-containing regimens 0.236 0.224 0.248 9. Forns X, Lee SS, Valdes J, et al. Lancet Infect Dis. 2017;17(10):1062-1068. 10. Kwo P, Gitlin N, Nahass R, et al. Hepatology. 2016;64(2):370-380. local sources F0-F3 0.93 0.88 0.98 – Non-cirrhotic: EBR/GZR became dominant over OMB/PAR/RIT+DAS and GLE/PIB 11. Lawitz E, Sulkowski MS, Ghalib R, et al. Lancet. 2014;384(9956):1756-1765. • Utility values (Table 4) were obtained from the published literature F4 (compensated cirrhosis) 0.90 0.86 0.95 12. Abdurakhmanov D, Bakulin I, Bogomolov P, et al. Hepatology International. 2017;11(1):S305. DC 0.80 0.76 0.84 13. OLYSIO summary of product characteristics. Beerse, Belgium: Janssen-Cilag International NV. Model Outputs Probabilistic Sensitivity Analyses (Figure 2) 14. DAKLINZA summary of product characteristics. Anagni, Italy: Bristol-Myers Squibb.