Siponimod (Mayzent) is a sphingosine 1-phosphate receptor modulator. This submission relates to the Health Canada–approved indication for the treatment of adults with secondary-progressive multiple sclerosis (SPMS) with active disease, evidenced by relapses or imaging features characteristic of multiple sclerosis (MS) inflammatory activity, to delay the progression of physical disability. Siponimod is available as 0.25 mg and 2 mg film-coated tablets. Treatment has to be initiated over five days: dose titration starts with 0.25 mg once daily on day 1 and day 2, followed by once daily doses of 0.5 mg on day 3 (two tablets of 0.25 mg), 0.75 mg on day 4 (three tablets of 0.25 mg), and 1.25 mg on day 5 (five tablets of 0.25 mg), to reach the maintenance dose of 2 mg siponimod. If a titration dose is missed on one day during the first six days of treatment, treatment needs to be re-initiated. At the submitted prices of $22.39 per 0.25 mg and $89.32 per 2 mg tablet, the first-year costs of treatment are $32,444 and $32,622 annually thereafter.

Prior to Health Canada approval and the determination of the indication, the sponsor submitted a cost-utility analysis based on a Markov state-transition model comparing siponimod with interferons (IFNs) (Extavia, Rebif, Avonex, and Betaseron) in adults with SPMS. On request, the sponsor provided a model that included best supportive care (BSC) to fully explore the cost-effectiveness of siponimod. BSC consists of therapies used to control SPMS symptoms and does not include therapies that would alter disease progression. These non-pharmacological therapies that are used to manage SPMS symptoms would also be received by those who are receiving siponimod. Following Health Canada approval for siponimod restricted to adults with active disease, the sponsor submitted an additional analysis with revised parameter estimates and inclusion of natalizumab as a further comparator.

Contents

• Abbreviations
• Executive Summary
  • Background
  • Summary of Identified Limitations and Key Results
  • Conclusions
• Information on the Pharmacoeconomic Submission
  • Summary of Sponsor’s Pharmacoeconomic Submission
  • Sponsor’s Base Case
  • Summary of Sponsor’s Sensitivity Analyses
  • Limitations of Sponsor’s Submission
  • CADTH Reanalyses
  • Patient Input
  • Conclusions
• Appendix 1. Cost Comparison
• Appendix 2. Additional Information
• Appendix 3. Summary of Other Health Technology Assessment Reviews of Drug
• Appendix 4. Reviewer Worksheets
• 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.