Sapropterin (SAP) (Kuvan) is indicated in conjunction with a phenylalanine (Phe)-restricted diet to reduce blood Phe levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin (BH₄)-responsive phenylketonuria (PKU). The initial dosage is 20 mg/kg/day administered orally for a period of up to 1 month. Once responsiveness to sapropterin (SAP) has been established, the dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. The confidential price per 100 mg tablet is $33.00. Based on representative body weight values obtained from trials of SAP, and depending upon dosage, annual costs for an 11 kg patient were estimated at $12,000 to $36,000; for a 29 kg patient, $24,000 to $72,000; and for a 68 kg patient, $48,000 to $169,000.

SAP was originally submitted to the CADTH Common Drug Review (CDR) in 2010, and in January 2011, the Canadian Expert Drug Advisory Committee (CEDAC) issued a Final Recommendation that Kuvan not be listed. The key reason for the recommendation was that patient details were insufficient to identify a subpopulation for whom SAP may provide a significant clinical benefit that is cost-effective. A Request for Advice regarding SAP was submitted to CDR by CDR-participating drug plans in October 2011, which did not result in any changes to the recommendation. The basis for the current resubmission is the availability of new clinical evidence. Following the 2011 CEDAC recommendation, provincial reimbursement of Kuvan has occurred in Ontario (as of February 2013) and Saskatchewan (as of September 2013). The manufacturer states that reimbursement criteria in these provinces were developed with the understanding that new data would be forthcoming about the effectiveness and appropriate use of SAP to treat patients with PKU. The submitted price for SAP is the same as in the 2010 submission; however, a revised cost-effectiveness model was provided as part of the resubmission.

Contents

• Abbreviations
• Executive Summary
• Information on the Pharmacoeconomic Submission
  • 1. Summary of the Manufacturer’s Pharmacoeconomic Submission
  • 2. Manufacturer’s Base Case
  • 3. Limitations of Manufacturer’s Submission
  • 4. Conclusions
• Appendix 1. Cost Comparison
• Appendix 2. Summary of Key Outcomes
• Appendix 3. Additional Information
• Appendix 4. Reviewer Worksheets
• Appendix 5. Summary of Other Cost-Effectiveness Analyses
• Appendix 6. Summary of Long-Term Phenylketonuria Studies
• Appendix 7. Coverage of Phenylketonuria Formulas and Medical Foods Across Canada
• References

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 two clinical experts in metabolic/biochemical diseases who provided input on the conduct of the review and the interpretation of findings.

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.

The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.