Efficacy of Generic Oral Directly Acting Agents in Patients With Hepatitis C Virus Infection

S. Gupta; G. Rout; A. H. Patel; M. Mahanta; N. Kalra; P. Sahu; R. Sethia; A. Agarwal; G. Ranjan; S. Kedia; S. K. Acharya; B. Nayak; Shalimar

Disclosures

J Viral Hepat. 2018;25(7):771-778. 

In This Article

Abstract and Introduction

Abstract

Novel direct–acting antivirals (DAAs) are now the standard of care for the management of hepatitis C virus (HCV) infection. Branded DAAs are associated with high sustained virological response at 12 weeks post–completion of therapy (SVR12), but are costly. We aimed to assess the efficacy of generic oral DAAs in a real–life clinical scenario. Consecutive patients with known HCV infection who were treated with generic–oral DAA regimens (May 2015 to January 2017) were included. Demographic details, prior therapy and SVR12 were documented. Four hundred and ninety patients (mean age: 38.9 ± 12.7 years) were treated with generic DAAs in the study time period. Their clinical presentations included chronic hepatitis (CHC) in 339 (69.2%) of cases, compensated cirrhosis in 120 (24.48%) cases and decompensated cirrhosis in 31 (6.32%) cases. Genotype 3 was most common (n = 372, 75.9%) followed by genotype 1 (n = 97, 19.8%). Treatment naïve and treatment–experienced (defined as having previous treatment with peginterferon and ribavirin) were 432 (88.2%) and 58 (11.8%), respectively. Generic DAA treatment regimens included sofosbuvir in combination with ribavirin (n = 175), daclatasvir alone (n = 149), ribavirin and peginterferon (n = 80), ledipasvir alone (n = 43), daclatasvir and ribavirin (n = 37), and ledipasvir and ribavirin (n = 6). Overall SVR12 was 95.9% (470/490) for all treatment regimens. SVR12 for treatment naïve and experienced patients was 97.0% (419/432) and 87.9% (51/58), respectively, P = .005. High SVR12 was observed with various regimens, irrespective of genotype and underlying liver disease status. There were no differences in SVR12 with 12 or 24 weeks therapy. No major adverse event occurred requiring treatment stoppage. Generic oral DAAs are associated with high SVR rates in patients with HCV infection in a real–life clinical scenario.

Introduction

Hepatitis C virus (HCV) infection poses a significant public health concern with an estimated 2%–3% overall global prevalence, and 0.9%–1.9% prevalence in India.[1] The vast majority of patients (up to 80%) who have HCV develop chronic hepatitis that can progress to chronic liver disease, cirrhosis and hepatocellular carcinoma. Novel direct–acting antivirals (DAAs) are now the standard of care for the management of HCV infection. Moreover, recent HCV management guidelines recommend that all patients positive for HCV RNA be considered for therapy irrespective of the serum alanine aminotransferase levels and underlying liver disease status.[23] The World Health Organization (WHO) recently launched an initiative to eliminate viral hepatitis by 2030; and in order to achieve these goals, approximately 71 million HCV–positive patients need to be treated, mostly from low–income countries of Asia and Africa.[4]

In interferon–free clinical trials, branded DAAs are associated with high sustained virological response at 12 weeks after completion of treatment (SVR12).[5–7] The cost of these branded drugs differs globally across countries and is out of reach in most developing countries, where treatment expenses are borne by the patients. Currently, in the United States, branded ledipasvir/sofosbuvir combination therapy (brand name Harvoni) costs approximately $1000 USD a pill, amounting to greater than $80 000 USD for a 12–week course of treatment. Gilead Sciences Inc, USA had given voluntary manufacturing licenses to several Indian companies including Cadila Zydus Ltd., Cipla Ltd., and Natco Pharma Ltd for generic production of sofosbuvir or its combinations with ledipasvir in 2014.[8] Indian generic manufacturers including Cipla Ltd., and Natco Pharma Ltd., also obtained sublicenses in 2015 for generic production of daclatasvir through Bristol–Meyers Squibb by way of the Medicines Patent Pool.[9] There are limited data on the efficacy of these generic brands across genotypes and varied clinical conditions. The aim of this study was to assess the efficacy of generic oral DAAs in a real–life clinical scenario and to compare efficacy across different treatment regimens, hepatitis C genotypes and severity of liver disease.

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