Age-related macular degeneration (AMD) is a degenerative disease of the macula. In Canada, about one million people currently have early AMD and approximately 250,000 have the advanced form of AMD. AMD is the leading cause of registered visual impairment in Canada. The prevalence of blindness due to AMD in Canada has been estimated at more than 100,000. There are two types of AMD: dry AMD and neovascular (wet) AMD (wAMD). While wAMD develops in only 10% to 20% of people with dry AMD, it accounts for more than 90% of those who have advanced vision loss. The hallmark of wAMD is choroidal neovascularization, which is an abnormal angiogenic process modulated by growth factors including vascular endothelial growth factor (VEGF).

Currently, there is no cure for wAMD. The goal of treatment is to minimize vision loss and disability in order to maintain independence. The first line of pharmacological therapy for wAMD in Canada is 0.5 mg ranibizumab, a monoclonal antibody that inhibits VEGF and that is administered monthly by intravitreal (IVT) injection. Pegaptanib and photodynamic therapy (PDT) using verteporfin are also indicated for the treatment of wAMD in Canada, but as these treatments are limited to stabilization of the disease and produce little to no improvement in vision, they are generally used as a second-line therapy in clinical practice. For instance, PDT is usually reserved for patients with wAMD for whom IVT injection is not suitable. Bevacizumab is a much larger antibody fragment derived from the same parent antibody as ranibizumab. It is not approved for treatment of wAMD in Canada, although it is used off-label for treating wAMD in patients who are ineligible for ranibizumab treatment coverage.

Aflibercept (Eylea) is a novel VEGF inhibitor that is indicated in Canada for the treatment of patients with wAMD. Aflibercept is supplied as a solution for IVT injection (40 mg/mL) at a dose of 2 mg every eight weeks after three initial monthly injections. The objective of this report was to review the beneficial and harmful effects of aflibercept at the dosing regimen recommended by Health Canada for the treatment of wAMD.

Contents

• Clinical Review Report
  • ABBREVIATIONS
  • EXECUTIVE SUMMARY
    • Introduction
    • Results and Interpretation
    • Other Considerations
    • Pharmacoeconomic Summary
    • 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 Exposure to Study Treatments
    • 3.5 Critical Appraisal
    • 3.6 Efficacy
    • 3.7 Harms
  • 4. DISCUSSION
    • 4.1 Summary of Available Evidence
    • 4.2 Interpretation of Results
    • 4.3 Other Considerations
  • 5. CONCLUSIONS
  • APPENDIX 1 PATIENT INPUT SUMMARY
  • APPENDIX 2 LITERATURE SEARCH STRATEGY
  • APPENDIX 3 EXCLUDED STUDIES
  • APPENDIX 4 DETAILED OUTCOME DATA
  • APPENDIX 5 VALIDITY OF OUTCOME MEASURES
  • APPENDIX 6 SUMMARY OF EXTENSION PHASE (96 WEEKS)
  • 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 CADTH Common Drug Review Analysis
    • 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
    • 2.3 Costs
  • 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
    • Patient input
  • 5. CONCLUSIONS
  • APPENDIX 1 COST COMPARISON TABLE OF ANTI-VEGF THERAPIES FOR WAMD
  • APPENDIX 2 OTHER HEALTH TECHNOLOGY ASSESSMENT FINDINGS
  • APPENDIX 3 SUMMARY OF KEY OUTCOMES
  • APPENDIX 4 ADDITIONAL INFORMATION
  • REFERENCES
• CDEC Final Recommendation
  • Recommendation
  • Reasons for the Recommendation
  • Background
  • Summary of CDEC Considerations
  • Other Discussion Points
  • Research Gaps

This review report was prepared by the Canadian Agency for Drugs and Technologies in Health (CADTH). In addition to CADTH staff, the review team included a clinical expert in specializing in the treatment of retinal disease (ophthalmologist) who provided input on the conduct of the review and the interpretation of findings.

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, Ontario, Prince Edward Island, Saskatchewan, and Yukon.