Cost–utility analysis of ledipasvir/sofosbuvir for the treatment of genotype 1 chronic hepatitis C in Japan

Abstract

Objective: Hepatitis C is the result of a ribonucleic acid (RNA) virus (hepatitis C virus; HCV). The Japan Society of Hepatology (JSH) estimated that 1.5–2 million people in Japan carry HCV. Six major HCV genotypes (GT) and a large number of subtypes have been described in the literature. In Japan, around 70% to 80% of people are infected with HCV genotype 1b. The progress of the disease primarily affects the liver and may lead to liver cirrhosis, hepatocellular carcinoma (HCC) and death. Sofosbuvir (SOF) is a nucleotide analogue NS5B inhibitor and ledipasvir (LDV) is an inhibitor of the HCV NS5A protein. They are combined in a single tablet regimen for the treatment of GT1 patients and resulted in sustained virological response (SVR) above 94% in large phase III trials. This analysis assesses the cost–utility of LDV/SOF in GT1 patients in Japan.

Research design and methods: A cohort of 10,000 patients was followed through a Markov model until they reached 100 years of age. GT1 treatment-naïve and experienced, non-cirrhotic and cirrhotic patients were studied separately. LDV/SOF was compared to several treatment regimens containing pegylated interferon (PEGIFN), telaprevir (TVR), simeprevir (SMV), daclatasvir (DCV), asunaprevir (ASV) and ribavirin (RBV). Discount rates of 2% were applied to costs and outcomes according to the Japanese guidelines.

Results: LDV/SOF was cost-effective against most comparators with incremental cost-effectiveness ratios (ICERs) below JPY 5,000,000. By applying a societal perspective, LDV/SOF was the dominant treatment strategy in all cases. Moreover, LDV/SOF reduced the number of cases of advanced liver disease. These results were robust to sensitivity analyses.

Conclusions: LDV/SOF was cost-effective compared to most of the currently recommended treatments. Furthermore, LDV/SOF extends treatments to HCV-infected patients who are ineligible for interferon and RBV-based regimens. LDV/SOF thus has the potential to help reduce the burden of HCV in Japan.

Keywords:

• Chronic hepatitis C infection
• Cost–utility analysis
• Daclatasvir
• Japan
• Ledipasvir/sofosbuvir
• Simeprevir
• Telaprevir

Note

Transparency

Declaration of funding

This study was funded by Gilead Sciences.

Declaration of financial/other relationships

A.I. has disclosed that he received grants and personal fees from Pfizer Japan Inc., Gilead Science KK, Milliman Inc. and Terumo Co. Ltd., grants from CSL Behring Japan Inc., Intuitive Surgical Inc., Fuji Film KK, and TOWA Pharmaceuticals Co. Ltd., personal fees from Novartis Pharma KK, AbbVie GK, CRECON Research and Consulting Inc., Sony Inc., Kanter Health Inc., Astellas Pharma KK, Chugai Pharaceutical Co. Ltd., Eli Lilly Japan KK, Health and Global Policy Institute, American Medical Devices and Diagnostics Manufacturers’ Association, Bristol-Myers Squibb KK, Abbott Japan KK, outside the submitted work. S.C., I.G., and L.M. have disclosed that they are employees of Mapi, a company that received consulting fees from Gilead. M.L. has disclosed that he is an employee of Junicon Inc., another company that received funding from Gilead to help conduct this study.

AI, WT (doctoral candidate), KT are affiliated to Department of Drug Policy & Management, Graduate School of Pharmaceutical Sciences, The University of Tokyo, an endowment laboratory supported with an unrestricted grant from TOWA Pharmaceuticals Co (Apr 2011-Sept 2015), and CSL Behring Japan Inc., Fuji Film K.K, Gilead Science K.K, Milliman Inc. and Terumo Co. Ltd. (Oct 2015-Sep 2020).

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Notice of correction

Please note that the authors' full given names have replaced the first name initial since the article was first published online (08 September 2016).

Notes

1. Harvoni is a registered trade name of Gilead Sciences, Foster City, US