June 2013

Volume 9, Issue 6, Supplement 3

A SPECIAL MEETING REVIEW EDITION

Advances in the Treatment of Hepatitis C Virus Infection From EASL 2013 The 48th Annual Meeting of the European Association for the Study of the Liver April 24–28, 2013 • Amsterdam, The Netherlands Special Reporting on: • Simeprevir Plus Peginterferon/Ribavirin Is Associated with a High SVR12 Rate in Treatment-Naive Patients with Genotype 1 Hepatitis C Virus Infection • Addition of Simeprevir to Peginterferon/Ribavirin Is Associated with Faster Resolution of Fatigue in Treatment-Naive Patients • Sofosbuvir Plus Ribavirin Demonstrates Significant Efficacy in Multiple HCV Genotype 2/3 Populations • Daclatasvir Plus Sofosbuvir with or without Ribavirin Yields 100% SVR24 Rate in Genotype 1 Patients Who Fail Telaprevir or Boceprevir • Addition of TG4040 Vaccine to Peginterferon/Ribavirin Increases Sustained Virologic Response Rate at 24 Weeks in Genotype 1 Hepatitis C Infection PLUS Meeting Abstract Summaries With Expert Commentary by: Ira M. Jacobson, MD Joan Sanford I. Weill Medical College at Cornell University New York, New York

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A D VA N C E S I N T H E T R E AT M E N T O F H E PAT I T I S C V I R U S I N F E C T I O N F R O M E A S L 2 0 1 3

Simeprevir Plus Peginterferon/Ribavirin Is Associated with a High SVR12 Rate in Treatment-Naive Patients with Genotype 1 Hepatitis C Virus Infection

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Table of Contents Simeprevir Plus Peginterferon/Ribavirin Is Associated with a High SVR12 Rate in Treatment-Naive Patients with Genotype 1 Hepatitis C Virus Infection

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Addition of Simeprevir to Peginterferon/Ribavirin Is Associated with Faster Resolution of Fatigue in Treatment-Naive Patients

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Sofosbuvir Plus Ribavirin Demonstrates Significant Efficacy in Multiple HCV Genotype 2/3 Populations

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Daclatasvir Plus Sofosbuvir with or without Ribavirin Yields 100% SVR24 Rate in Genotype 1 Patients Who Fail Telaprevir or Boceprevir

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Addition of TG4040 Vaccine to Peginterferon/Ribavirin Increases Sustained Virologic Response Rate at 24 Weeks in Genotype 1 Hepatitis C Infection

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Commentary Ira M. Jacobson, MD

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imeprevir is an investigational hepatitis virus (HCV) NS3/4A protease inhibitor that showed potent antiviral activity against multiple genotypes in preclinical studies and allows once-daily dosing. Two international, phase IIb, randomized, double-blind, placebo-controlled studies in patients with genotype 1 HCV demonstrated the efficacy and safety of simeprevir in combination with peginterferon/ribavirin in treatment-naive patients (PILLAR trial)1 and treatment-experienced patients (ASPIRE trial).2 In both trials, the addition of simeprevir to peginterferon/ribavirin was associated with high sustained virologic response (SVR) rates with little additional toxicity over peginterferon/ribavirin alone. Based on these findings, 2 randomized, double-blind, placebocontrolled phase III trials, QUEST-1 and QUEST-2, were undertaken to evaluate the efficacy and safety of simeprevir plus peginterferon/ribavirin in treatment-naive patients with HCV genotype 1 infection.3,4 Results of both trials were presented at the 48th Annual Meeting of the European Association for the Study of the Liver (EASL 2013).

QUEST-1: Simeprevir Plus Peginterferon/Ribavirin Indexed through the National Library of Medicine (PubMed/Medline), PubMed Central (PMC), and EMBASE Disclaimer Every effort has been made to ensure that drug usage and other information are presented accurately; however, the ultimate responsibility rests with the prescribing physician. Gastro-Hep Communications, Inc., and the participants shall not be held responsible for errors or for any consequences arising from the use of information contained herein. Readers are strongly urged to consult any relevant primary literature. No claims or endorsements are made for any drug or compound at present under clinical investigation. ©2013 Gastro-Hep Communications, Inc. 611 Broadway, Suite 310, New York, NY 10012. Printed in the USA. All rights reserved, including the right of reproduction, in whole or in part, in any form.

Results of QUEST-1 were presented by Ira M. Jacobson MD, Chief of the Division of Gastroenterology and Hepatology and Vincent Astor Distinguished Professor of Medicine at the Joan Sanford I. Weill Medical College of Cornell University in New York City. Simeprevir 150 mg once daily plus peginterferon/ribavirin (n=264) was compared with placebo plus peginterferon/ribavirin (n=130)

in treatment-naive patients with HCV genotype 1 infection. Patients were stratified by HCV genotype subtype and the interleukin-28B (IL28B) genotype. Patients received simeprevir or placebo for the first 12 weeks of peginterferon/ribavirin therapy. Responseguided therapy was used to determine the total treatment duration. In the simeprevir arm, treatment duration was 24 weeks in patients with an HCV RNA load of less than 25 IU/mL at Week 4 and an undetectable HCV RNA load at Week 12. Treatment duration was 48 weeks in all other patients. All patients in the placebocontrolled arm received peginterferon/ ribavirin for 48 weeks. Patient characteristics were well balanced between arms. Approximately 56% of patients were male. Patients were predominately white, with a median age of 48 years, 29% had the IL-28B CC genotype, and approximately 56% had genotype 1a infection. Cirrhosis was present in approximately 12% of patients. The addition of simeprevir to peginterferon/ribavirin was associated with a significant improvement in efficacy over peginterferon/ribavirin alone, with SVR at Week 12 (SVR12) rates of 80% and 50%, respectively (P