To address the identified limitations presented in Table 2, CADTH assumed a 10-year treatment duration for voretigene neparvovec, used data from crossover patients in Study 301 to inform short-term transition probabilities, and updated the sponsor’s utility estimates with the values provided by clinical experts consulted by CADTH. The CADTH reanalysis of the sponsor’s economic model estimated that the incremental cost-effectiveness ratio (ICER) for voretigene neparvovec compared with best supportive care (BSC) was $200,477 per quality-adjusted life-year (QALY) gained. To achieve an ICER of $50,000 per QALY compared with BSC, the price of voretigene neparvovec would need to be reduced by more than 74%.

The submitted price of voretigene neparvovec is a key driver of overall costs and of the ICER within the model. While the cost of voretigene neparvovec is known and is incurred at the beginning of the model time horizon, the majority (96%) of the clinical benefit (QALYs gained) was estimated through extrapolation beyond the observed trial period (Study 301). The extrapolations were made based on several assumptions with high levels of untestable uncertainty. Estimates for treatment effectiveness and natural history were further associated with both significant parameter and structural uncertainties.

Since the expected duration of the treatment effect of voretigene neparvovec and the utility estimates were also key drivers in the model, CADTH conducted additional scenario analyses that highlighted a wide range of plausible ICER estimates across different durations of treatment effect. Since most of the benefit estimated in the model originates from the improvements in quality of life as opposed to increased life expectancy, the results are sensitive to the choice of utility weights. Previous studies in different clinical settings have shown that valuation of health states by proxies typically underestimates the utility weight in chronic disability health states compared with those elicited by the patients themselves. In such instances, this would overestimate differences in quality of life between voretigene neparvovec and BSC, which would result in a higher ICER for voretigene neparvovec. Together, these limitations indicate that the cost-effectiveness results should be cautiously interpreted.

Contents

• Abbreviations
• Executive Summary
  • Conclusions
• Stakeholder Input Relevant to the Economic Review
• Economic Review
  • Economic Evaluation
  • Issues for Consideration
  • Overall Conclusions
• Appendix 1. Cost Comparison Table
• Appendix 2. Submission Quality
• Appendix 3. Additional Information on the Submitted Economic Evaluation
• Appendix 4. Additional Details on the CADTH Reanalyses and Sensitivity Analyses of the Economic Evaluation
• Appendix 5. Submitted Budget Impact Analysis and CADTH Appraisal
• References

Version: Final

Disclaimer: The information in this document 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. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.

While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.

CADTH is not responsible for any errors, omissions, 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 contents of this document or any of the source materials.

This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.

Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third-party supplier of information.

This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own 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.