Telaprevir-Based Therapy for Chronic Hepatitis C in Japan: A Summary of Clinical Study Results

Mini Review

J Hepat Res. 2015;2(1): 1020.

Telaprevir-Based Therapy for Chronic Hepatitis C in Japan: A Summary of Clinical Study Results

Ichimaro Yamada1* and Yoshiyuki Nakayasu2

1R&D Transformation Department, Mitsubishi Tanabe Pharma Corporation, Japan

2Development Division, Mitsubishi Tanabe Pharma Corporation, Japan

*Corresponding author: Ichimaro Yamada, R&D Transformation Department, Mitsubishi Tanabe Pharma Corporation, 1-1-1, Marunouchi, Chiyodaku, Tokyo, Japan

Received: February 20, 2015; Accepted: March 27, 2015; Published: April 07, 2015

Abstract

We summarized the clinical study results of Telaprevir (TVR) in combination with peginterferon and ribavirin for Japanese patients with genotypes 1 and 2 Hepatitis C Virus (HCV) infection. The Sustained Virological Response (SVR24) rates of relapsers and non-responders with genotype 1 HCV infection were 88.1% (96/109) and 34.4% (11/32), respectively. On the other hand, the SVR24 rates of relapsers and non-responders with genotype 2 HCV infection were 88.0% (95/108) and 50.0% (5/10), respectively. These results demonstrated that high SVR rates are achieved with TVR-based triple therapy in difficultto- treat patients with genotype 2 as well as genotype 1 HCV infection. The majority of Japanese patients with HCV is older and has a lower weight than patients in the United States and Europe. A post-marketing surveillance study of patients with genotype 1 HCV infection showed the SVR rates of naïve patients, relapsers, and non-responders treated at a dose of 2250 mg/day and less than 2250 mg/day of TVR were as follows: 92.1% (680/738) and 90.7% (223/246) in naïve patients; 91.9% (719/782) and 88.9% (297/334) in relapsers; and 74.8% (243/325) and 60.4% (81/134) in non-responders, respectively. These results suggest that the lower dose regimen of TVR maybe a treatment alternative in older and lower weight Japanese patients.

Keywords: Telaprevir; Hepatitis C virus; Genotype 1; Genotype 2; Sustained virological response; Japanese patient

TVRAbbreviations

TVR: Telaprevir; Peg-IFN: Peg Interferon alfa-2b; RBV: Ribavirin; DAA: Direct Acting Antiviral; HCV: Hepatitis C Virus; SVR: Sustained Virological Response; RVR: Rapid Virological Response; ETR; End-Of-Treatment Response

Introduction

Hepatitis C Virus (HCV) is estimated to infect approximately 185 million people worldwide. In Japan, there are estimated to be about 2 million HCV carriers. Genotype 1b and genotype 2 accounts for approximately 70% and 30% of chronic HCV infections in Japan, respectively. In 2011, the first-generation direct-acting antiviral agent Telaprevir (TVR) with Peg Interferon (Peg-IFN) and Ribavirin (RBV) was approved for treatment of chronic HCV genotype 1 patients in the United States and Europe. In Japan, TVR was approved in September 2011 and has been marketed since November 2011. Furthermore, in September 2014, only in Japan, TVR for 12 weeks plus Peg-IFN and RBV for 24 weeks (T12/PR24) was approved for patients with genotype 2 HCV infection who experienced relapses or were nonresponders to a prior IFN-based regimen. Recently, a number of Direct Acting Antiviral Agents (DAAs) (second-generation protease inhibitors, NS5B polymerase inhibitors, and NS5A inhibitors) are being studied in advanced clinical trials, and some DAAs have been marketed. These DAAs have a different resistance profile from the first-generation protease inhibitor TVR. We summarized the clinical study results of T12/PR24for Japanese patients with genotypes 1 and 2 HCV infection.

Clinical study results

The patients were excluded if they had cirrhosis. In treatmentnaïve patients with genotype 1 HCV infection, Sustained Virological Response (SVR24) was achieved more frequently withT12/PR24 than with Peg-IFN and RBV for 48 weeks (PR48) (73.0% vs. 49.2%, P=0.0020) [1]. Relapsers were defined as patients who had been previously treated for Chronic Hepatitis C (CHC) and had undetectable HCV RNA during IFN or Peg-IFN therapy (including combination with RBV). Non-responders were defined as patients who were previously treated for CHC and had never had undetectable HCV RNA for more than 24 weeks with IFN or Peg-IFN therapy (including combination with RBV).The SVR24 rates in relapsers and non-responders with genotype 1 HCV infection were 88.1% (96/109) and 34.4% (11/32), respectively [2]. The SVR24 rates for the treatmentnaïve patients and non-responders who received more than the 40% RBV cumulative dose were 80.6% (54/67) and 45.5% (10/22), respectively [1, 2]. The SVR24 rate for the relapsers who received more than the 20% RBV cumulative dose was 92.8% (90/97) [2]. Anemia and skin disorder were frequent adverse events that led to discontinuation of all the study drugs. Discontinuation rates of all the study drugs due to anemia and skin disorder were 7.5% (20/267) and 4.5% (12/267) in T12/PR24, and 4.8% (3/63) and 3.2% (2/63) in PR48, respectively [1,2]. The SVR24 rates for relapsers and non-responders with genotype 2 HCV infection were 88.0% (95/108) and 50.0% (5/10), respectively. The SVR24 rates after completing the treatment protocol for relapsers and non-responders were 98.4% (61/62) and 100% (5/5), respectively. The SVR24 rates did not differ significantly between patients with rs8099917 TT and non-TT [3]. The overall safety profiles of TVR-based regimens were similar for Japanese patients with genotype 1 and 2 HCV infection who experienced treatment failure.

Citation: Yamada I and Nakayasu Y. Telaprevir-Based Therapy for Chronic Hepatitis C in Japan: A Summary of Clinical Study Results. J Hepat Res. 2015;2(1): 1020. ISSN:2381-9057