pan-canadian Oncology Drug Review Final Economic Guidance Report Ibrutinib (Imbruvica) for Mantle Cell Lymphoma July 19, 2016
DISCLAIMER Not a Substitute for Professional Advice This report is primarily intended to help Canadian health systems leaders and policymakers make well-informed decisions and thereby improve the quality of health care services. While patients and others may use this report, they are made available for informational and educational purposes only. This report should not be used 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, or as a substitute for professional medical advice. Liability pcodr does not assume any legal liability or responsibility for the accuracy, completeness or usefulness of any information, drugs, therapies, treatments, products, processes, or services disclosed. The information is provided "as is" and you are urged to verify it for yourself and consult with medical experts before you rely on it. You shall not hold pcodr responsible for how you use any information provided in this report. Reports generated by pcodr are composed of interpretation, analysis, and opinion on the basis of information provided by pharmaceutical manufacturers, tumour groups, and other sources. pcodr is not responsible for the use of such interpretation, analysis, and opinion. Pursuant to the foundational documents of pcodr, any findings provided by pcodr are not binding on any organizations, including funding bodies. pcodr hereby disclaims any and all liability for the use of any reports generated by pcodr (for greater certainty, "use" includes but is not limited to a decision by a funding body or other organization to follow or ignore any interpretation, analysis, or opinion provided in a pcodr report). FUNDING The pan-canadian Oncology Drug Review is funded collectively by the provinces and territories, with the exception of Quebec, which does not participate in pcodr at this time. 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW ii
INQUIRIES Inquiries and correspondence about the pan-canadian Oncology Drug Review (pcodr) should be directed to: pan-canadian Oncology Drug Review 154 University Avenue, Suite 300 Toronto, ON M5H 3Y9 Telephone: 613-226-2553 Toll Free: 1-866-988-1444 Fax: 1-866-662-1778 Email: info@pcodr.ca Website: www.cadth.ca/pcodr 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW iii
TABLE OF CONTENTS DISCLAIMER... ii FUNDING... ii INQUIRIES... iii TABLE OF CONTENTS... iv 1 ECONOMIC GUIDANCE IN BRIEF... 1 1.1 Submitted Economic Evaluation... 1 1.2 Clinical Considerations... 3 1.3 Submitted and EGP Reanalysis Estimates... 4 1.4 Detailed Highlights of the EGP Reanalysis... 5 1.5 Evaluation of Submitted Budget Impact Analysis... 7 1.6 Conclusions... 7 2 DETAILED TECHNICAL REPORT... 9 This section outlines the technical details of the pcodr Economic Guidance Panel s evaluation of the economic evidence that is summarized in Section 1. Pursuant to the pcodr Disclosure of Information Guidelines, this section is not eligible for disclosure. It was provided to the pcodr Expert Review Committee (perc) for their deliberations. 3 ABOUT THIS DOCUMENT... 10 REFERENCES... 11 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW iv
appetite, weight loss, and fatigue. Patients also noted that ibrutinib brought their disease under control and made them feel better again. The submitted economic model did consider factors that were important and relevant to patients: quality of life and adverse events. Summary of Provincial Advisory Group (PAG) input relevant to the economic analysis PAG considered the following factors would be important to consider if implementing a funding recommendation for ibrutinib which are relevant to the economic analysis: Enablers to implement of ibrutinib include: New treatment option that is an oral drug. Key barriers to implement of ibrutinib include: Small number of patients relative to other cancers but potentially large number of prevalent patients; Unknown treatment duration and number of patients eligible for treatment; High cost of ibrutinib. These factors relevant to PAG were considered in the economic analysis. 1.3 Submitted and EGP Reanalysis Estimates According to the economic analysis that was submitted by Janssen Inc. when ibrutinib is compared with the standard of care treatment mix: The extra cost of ibrutinib is $173,687 (ΔC). Costs considered in the analysis included drugs, disease management, and adverse events. The extra clinical effect of ibrutinib is 0.86 quality-adjusted life years and 1.10 life years gained (ΔE). The clinical effect considered in the analysis was based on progression-free survival, overall survival, incidence of adverse events, and utilities. The submitter estimated that the incremental cost-effectiveness ratio was $201,671 per QALY. The submitter also provided another approach (using the efficacy of temsirolimus as a proxy for the efficacy of SOC, instead of efficacy for SOC using the indirect comparison). With this approach, the submitter estimated that the incremental cost-effectiveness ratio was $173,165 per QALY. The EGP considered both approaches and determined that the indirect comparison approach provide a more reasonable comparison in the Canadian context. The EGP used the economic model submitted by Janssen Inc. and performed reanalyses. Detailed highlights of the EGP Reanalysis is provided in Section 1.4. The EGP estimates differed from the submitted estimates. A comparison between the submitted model and the EGP reanalysis results is provided in Table 1.3. 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW 4
the OS results were not statistically significant (the CI crossed 1.0); and a shortened time horizon (from 10 years to 5 years). Other minor effect drivers in the model include utilities. Overall conclusions of the submitted model: Model Structure o The economic model provided is adequate, however, the model did not consider inputs such as wastage, disease management costs, and subsequent therapies. Data Inputs o The make-up of the standard of care treatment mix used in the economic model is different from the investigator choice treatment mix in the OPTIMAL trial. The make-up of the treatment mix used in the economic analysis is different than the mix of treatments that was reported in the OPTIMAL trial. The CGP noted the proportion of included comparators such as bendamustinerituximab (BR) may be too high and not reflective of Canadian clinical practice. Otherwise, the mix of treatments was appropriate. Patient Input o The factors relevant to patients were taken into consideration in the economic model. Overall o Overall, the model is adequate, however, there is some degree of uncertainty present. For example, there exists uncertainty in the HR for OS; and the choice of time horizon due to extrapolation of OS and PFS data beyond the trial follow-up period. 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW 8
2 DETAILED TECHNICAL REPORT This section outlines the technical details of the pcodr Economic Guidance Panel s evaluation of the economic evidence that is summarized in Section 1. Pursuant to the pcodr Disclosure of Information Guidelines, this section is not eligible for disclosure. It was provided to the pcodr Expert Review Committee (perc) for their deliberations 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW 9
3 ABOUT THIS DOCUMENT This Economic Guidance Report was prepared by the pcodr Economic Guidance Panel and supported by the pcodr Lymphoma & Myeloma Clinical Guidance Panel and the pcodr Methods Team. This document is intended to advise the pcodr Expert Review Committee (perc) regarding resource implications and the cost-effectiveness of ibrutinib (Imbruvica) for relapsed or refractory mantle cell lymphoma. A full assessment of the clinical evidence of ibrutinib (Imbruvica) for relapsed or refractory mantle cell lymphoma is beyond the scope of this report and is addressed by the relevant pcodr Clinical Guidance Report. Details of the pcodr review process can be found on the pcodr website (www.cadth.ca/pcodr). pcodr considers it essential that perc recommendations be based on information that can be publicly disclosed. Information included in the Economic Guidance Report was handled in accordance with the pcodr Disclosure of Information Guidelines. There was no non-disclosable information in the Economic Guidance Report provided to perc for their deliberations. This Final Economic Guidance Report is publicly posted at the same time that a perc Final Recommendation is issued. The Final Economic Guidance Report supersedes the Initial Economic Guidance Report. Note that no revisions were made in between posting of the Initial and Final Guidance Reports. The Economic Guidance Panel is comprised of economists selected from a pool of panel members established by the pcodr Secretariat. The panel members were selected by the pcodr secretariat, as outlined in the pcodr Nomination/Application Information Package and the Economic Guidance Panel Terms of Reference, which are available on the pcodr website (www.cadth.ca/pcodr). Final selection of the pool of Economic Guidance Panel members was made by the perc Chair in consultation with the pcodr Executive Director. The Economic Guidance Panel is editorially independent of the provincial and territorial Ministries of Health and the provincial cancer agencies. 2016 pcodr PAN-CANADIAN ONCOLOGY DRUG REVIEW 10
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