Spinal muscular atrophy (SMA) is a severe neuromuscular disease and is the leading genetic cause of infant death. It is characterized by the degeneration of alpha motor neurons in the anterior horn of the spinal cord, leading to progressive muscle weakness. The most common form of SMA, 5q SMA, makes up more than 95% of all cases and is an autosomal recessive disorder caused by homozygous deletion or deletion and mutation of the alleles of the survival motor neuron 1 gene. SMA is a rare disease and estimates of its incidence and prevalence vary between studies. The incidence of SMA is often cited as being approximately 10 in 100,000 live births. Four clinical subtypes of SMA are described: SMA type I makes up about 60% of SMA diagnoses where patients show symptoms before six months of age, never achieve the motor milestone of sitting unsupported, and generally do not survive past two years of age due to respiratory failure. Those with SMA type II achieve the milestone of sitting unsupported, but never walk independently; symptoms generally appear between six and 18 months after birth and most patients will survive past the age of 25, with life expectancy improved by aggressive supportive care. SMA type III makes up approximately 10% to 20% of SMA cases3 and presents between 18 months of age and adulthood. These patients are able to walk independently at some point in their lives and typically have a normal life expectancy. SMA type IV constitutes a very small proportion of SMA cases, has an adult onset, and is the mildest form of the disease. Although muscle weakness is present, these patients retain the ability to walk, have a normal life expectancy, and do not suffer from respiratory or nutritional issues.

Nusinersen (Spinraza) is a solution for intrathecal injection, indicated for the treatment of 5q SMA. It is available as a single-use solution in a 5 mL vial size (12 mg) administered intrathecal by lumbar puncture. The recommended dose is initial treatment with four loading doses, with the first three loading doses administered at 14-day intervals (day 0, day 14, and day 28), and a final loading dose approximately 30 days after the third loading dose (day 63); maintenance treatment is 12 mg every four months. At the marketed price of $118,000 per 5 mL vial, the annual cost of treatment with nusinersen ranges from $354,000 for maintenance treatment (three doses) to $708,000 in the first year (six doses). The manufacturer’s listing request is per the Health Canada indication.

As part of a resubmission the manufacturer provided new clinical information relating to different subpopulations with SMA (see CADTH Common Drug Review [CDR] Clinical Report). The manufacturer, however, did not provide a revised economic submission nor did it provide any discussion relating to the new clinical information and how this may impact the findings of the economic review based on the original submission. Thus, the CDR economic review remains unchanged with no further data provided to refute the original issues or limitations identified.

Contents

• Abbreviations
• Executive Summary
  • Background
  • Summary of Identified Limitations and Key Results
  • Conclusions
• Information on the Pharmacoeconomic Submission
  • Summary of the Manufacturer’s Pharmacoeconomic Submission
  • Manufacturer’s Base Case
  • Summary of Manufacturer’s Sensitivity 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 HTA 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.