OnabotulinumtoxinA (Ona A; Botox) powder for intramuscular injection solution is a neuromuscular paralytic agent derived from the fermentation of Clostridium botulinum type A and is one of several immunologically distinct serotypes of botulinum neurotoxin. It is indicated for the prophylaxis of headaches in adults with chronic migraine (CM) who have headaches that occur at least 15 days per month and last four hours a day or longer. Ona A is administered as a minimum of 31 injections and a maximum of 39 injections of five Allergan units (U) per injection to the head and neck (total: 155 U to 195 U per administration). The recommended retreatment schedule is every 12 weeks. Ona A is available in 50 U, 100 U, and 200 U vial sizes, at a cost of $178.50, $357.00, and $714.00 per vial, respectively ($3.57 per U). CADTH Canadian Drug Expert Committee previously reviewed Ona A in 2014 for CM and provided a do-not-list recommendation due to significant limitations of the underlying clinical evidence.

The manufacturer submitted a cost-utility analysis for this resubmission that was similar to the initial submission in 2014. In the current submission, the manufacturer compared Ona A with best supportive care (BSC) for the prophylaxis of headaches in adults with CM over a three-year time horizon. The manufacturer also compared Ona A with topiramate in a pairwise scenario analysis to account for changes in clinical practice since the original submission. The Markov model in the resubmission attempted to address some of the previous limitations identified by CADTH by considering additional health care resource use and costs, and added health states to model headache frequency changes in patients who discontinue treatment. The manufacturer modelled 13 health states: six headache frequency health states (0 to 3, 4 to 9, 10 to 14, 15 to 19, 20 to 23, and 24 to 28 headache days per month [HDPM]) for each treatment status (i.e., on treatment or discontinued treatment due to treatment failure) and a death state. Patients entered the model in the various health states based on headache frequency distribution from a pooled analysis of the PREEMPT trials, and transitioned between states every 12 weeks. Similar to the original submission, efficacy and discontinuation data from the PREEMPT trials were pooled and used to inform transition probability for Ona A and BSC; placebo was used as a proxy for BSC. The manufacturer modelled response-based discontinuation based on current clinical practice, in which patients who do not experience a reduction of at least 50% in headache frequency after the initial 24 weeks discontinue treatment. Patients discontinuing Ona A or BSC were assumed to be treated with BSC (patients treated with BSC effectively did not discontinue).

The manufacturer reported that Ona A was associated with an additional cost of $3,430 and generated an additional 0.10 quality-adjusted life-years (QALYs) compared with BSC, resulting in an incremental cost-utility ratio (ICUR) of $34,407 per QALY. At a willingness-to-pay threshold of $50,000 per QALY, the manufacturer reported that Ona A was associated with a 64% probability of being the optimal intervention compared with BSC.

Contents

• Abbreviations
• Executive Summary
  • Background
  • Summary of Identified Limitations and Key Results
  • Conclusions
• Information on the Pharmacoeconomic Submission
  • Summary of the Manufacturer’s Pharmacoeconomic Resubmission
  • Manufacturer’s Base Case
  • Summary of Manufacturer’s Key Scenario Analysis
  • Summary of Manufacturer’s Additional Analyses
  • Limitations of Manufacturer’s Submission
  • CADTH Common Drug Review Reanalyses
  • Issues for Consideration
  • 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 (with redactions)

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.