Hepatitis C virus (HCV) infection is caused by an enveloped, single-stranded, linear ribonucleic acid (RNA) virus of the Flaviviridae family. Before 2011, pegylated interferon plus ribavirin (PR) was the gold standard of therapy to inhibit viral replication in patients with chronic hepatitis C (CHC). Approximately one-half of patients with genotype 1 CHC, the most prevalent type of CHC in Canada, could expect to achieve a sustained viral response (SVR) with PR therapy.

Simeprevir is a direct-acting antiviral (DAA) agent against HCV; it inhibits the HCV NS3/4A protease through a non-covalent, induced-fit binding into the active site of the NS3 protease.¹ In Canada, simeprevir is indicated for the treatment of CHC genotype 1 infection, in combination with peginterferon alfa and ribavirin in adults with compensated liver disease, including cirrhosis, who are treatment-naive or who have failed previous interferon therapy (pegylated or non-pegylated) with ribavirin. The recommended dosage is a single 150 mg capsule taken orally once daily in combination with both peginterferon alfa and ribavirin (triple therapy) for 12 weeks, followed by peginterferon alfa and ribavirin (dual therapy) for a further 12 to 36 weeks (the duration is dependent upon the patient’s characteristics and response to treatment; i.e., response-guided treatment).

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Pharmacoeconomic Summary
    • Interpretations and Key Limitations
    • Issues for Consideration
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Disease Prevalence and Incidence
    • 1.2. Standards of Therapy
    • 1.3. Drug
  • 2. OBJECTIVES AND METHODS
    • 2.1. Objectives
    • 2.2. Methods
  • 3. RESULTS
    • 3.1. Findings From the Literature
    • 3.2. Included Studies
    • 3.3. Patient Disposition
    • 3.4. Critical Appraisal
    • 3.5. Efficacy
    • 3.6. Harms
  • 4. DISCUSSION
    • 4.1. Summary of Available Evidence
    • 4.2. Interpretation of Results
  • 5. CONCLUSIONS
  • APPENDIX 1. PATIENT INPUT SUMMARY
    • 1. Brief Description of Patient Group(s) Supplying Input
    • 2. Condition and Current Therapy-Related Information
    • 3. Related Information About the Drug Being Reviewed
    • 4. Additional Information
  • APPENDIX 2. LITERATURE SEARCH STRATEGY
    • Database Search
  • APPENDIX 3. EXCLUDED STUDIES
  • APPENDIX 4. DETAILED OUTCOME DATA
  • APPENDIX 5. VALIDITY OF OUTCOME MEASURES
    • Objective
    • Background/findings
    • Summary
  • APPENDIX 6. SUMMARY OF CRICITAL APPRAISAL OF THE NETWORK META-ANALYSIS
    • 1. Objective
    • 2. Summary of Network Meta-analysis
    • 3. Critical Appraisal of Network Meta-analysis
    • 4. Summary
  • APPENDIX 7. ADDITIONAL INFORMATION RECEIVED FROM THE MANUFACTURER RELATED TO THE SUBMITTED NETWORK META-ANALYSIS
    • 1. Objective
    • 2. Summary
    • 3. Discussion
    • 4. Summary
  • APPENDIX 8. OVERVIEW OF SAFETY AND EFFICACY OF SOFOSBUVIR
    • Objective
    • Findings
    • Summary
  • APPENDIX 9. VIROLOGIC STOPPING CRITERIA IN INCLUDED STUDIES
  • REFERENCES
• Pharmacoeconomic Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY OF THE PHARMACOECONOMIC SUBMISSION
    • Background
    • Summary of Economic Analysis
    • Results of Manufacturer’s Analysis
    • Interpretations and Key Limitations
    • Results of CDR Analysis
    • Issues for Consideration
    • Conclusions
  • 1. INTRODUCTION
    • 1.1. Study Question
    • 1.2. Treatment
    • 1.3. Comparators
    • 1.4. Type of Economic Evaluation
    • 1.5. Population
  • 2. METHODS
    • 2.1. Model Structure
    • 2.2. Clinical Inputs
  • 3. RESULTS
    • 3.1. Manufacturer’s Base Case
    • 3.2. Summary of the Manufacturer’s Sensitivity Analyses
    • 3.3. CADTH Common Drug Review Analyses
  • 4. DISCUSSION
    • 4.1. Issues for Consideration
    • 4.2. Patient Input
  • 5. CONCLUSIONS
  • APPENDIX 1. COST COMPARISON TABLE
  • APPENDIX 2. SUMMARY OF KEY OUTCOMES
  • APPENDIX 3. SUMMARY OF COST-MINIMIZATION ANALYSIS
    • Key Limitations
    • Summary of Findings
  • APPENDIX 4. ADDITIONAL INFORMATION
  • REFERENCES
• CDEC FINAL RECOMMENDATION
  • Recommendation
  • Reasons for the Recommendation
  • Background
  • Other Discussion Points
  • Research Gaps

This report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). Through the CADTH Common Drug Review (CDR) process, CADTH undertakes reviews of drug submissions, resubmissions, and requests for advice, and provides formulary listing recommendations to all Canadian publicly funded federal, provincial, and territorial drug plans, with the exception of Quebec.

The report contains an evidence-based clinical and/or pharmacoeconomic drug review, based on published and unpublished material, including manufacturer submissions; studies identified through independent, systematic literature searches; and patient group submissions. In accordance with CDR Update — Issue 87, manufacturers may request that confidential information be redacted from the CDR Clinical and Pharmacoeconomic Review Reports.

The information in this report is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. The information in this report should not be used as a substitute for the application of clinical judgment with respect to the care of a particular patient or other professional judgment in any decision-making process, nor is it intended to replace professional medical advice. While CADTH has taken care in the preparation of this document to ensure that its contents are accurate, complete, and up-to-date as of the date of publication, CADTH does not make any guarantee to that effect. CADTH is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in the source documentation. CADTH is not responsible for any errors or omissions or injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the information in this document or in any of the source documentation.

This document is intended for use in the context of the Canadian health care system. Other health care systems are different; the issues and information related to the subject matter of this document may be different in other jurisdictions and, if used outside of Canada, it is at the user’s risk. This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.

CADTH takes sole responsibility for the final form and content of this document, subject to the limitations noted above. The statements and conclusions in this document are those of CADTH and not of its advisory committees and reviewers. The statements, conclusions, and views expressed herein do not necessarily represent the views of Health Canada or any Canadian provincial or territorial government. Production of this document is made possible by financial contributions from Health Canada and the governments of Alberta, British Columbia, Manitoba, New Brunswick, Newfoundland and Labrador, Northwest Territories, Nova Scotia, Nunavut, Prince Edward Island, Saskatchewan, and Yukon.