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PharmacoEconomics

, Volume 36, Issue 11, pp 1299–1308 | Cite as

Etelcalcetide for Treating Secondary Hyperparathyroidism: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal

  • Micah Rose
  • Jonathan Shepherd
  • Petra Harris
  • Karen Pickett
  • Joanne Lord
Review Article

Abstract

The manufacturer of the calcimimetic drug etelcalcetide was invited to make an evidence submission as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) programme. Within this submission, they reported evidence on the clinical and cost effectiveness of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis. The Southampton Health Technology Assessments Centre (SHTAC), part of the Wessex Institute at the University of Southampton, was the independent Evidence Review Group (ERG) commissioned to appraise the company’s submission. This article describes the ERG’s review and critique of the company’s submission and summarises the NICE Appraisal Committee’s subsequent guidance (issued in June 2017). The clinical-effectiveness evidence submitted by the company consisted of two double-blind, randomised controlled trials (RCTs) comparing etelcalcetide with placebo, one RCT comparing etelcalcetide with cinacalcet, two single-arm extension studies of the above trials, and one single-arm study evaluating the effect of switching from cinacalcet to etelcalcetide. No study specifically examined the population specified in the NICE appraisal scope: patients refractory to standard therapy with phosphate binders and vitamin D (PBVD). None of these trials were designed to collect long-term efficacy data for outcomes such as mortality, bone fractures, cardiovascular events, or parathyroidectomies. Instead, biomarker data from the trials were mapped to long-term outcomes by an assumed linear relationship between the trial outcome, reduction of parathyroid hormone (PTH) by > 30%, and the log-hazard ratios for the occurrence of clinical events derived from a large, long-term RCT of cinacalcet (the EVOLVE trial). After submission of a confidential Patient Access Scheme (PAS) discount reducing etelcalcetide drug costs, the incremental cost-effectiveness ratio (ICER) for etelcalcetide versus cinacalcet was £14,778 per quality-adjusted life-year (QALY) gained in the company’s base case. While this value is lower than the NICE threshold range of £20,000 and £30,000 per QALY gained, it was the opinion of the ERG that the ICER was highly uncertain due to efficacy data limitations for etelcalcetide, inadequate synthesis of clinical-effectiveness evidence, and strong assumptions connecting short-term biomarker data with long-term clinical outcomes. The ERG produced an alternative base case for etelcalcetide versus cinacalcet, with an ICER of £22,400 per QALY gained, also subject to uncertainty. The NICE Appraisal Committee recommended etelcalcetide as an option for the treatment of SHPT in adults with CKD only if treatment with a calcimimetic is indicated and cinacalcet is not suitable, subject to the company’s provision of the agreed PAS discount.

Notes

Acknowledgements

The authors are very grateful to the clinical experts who provided them with information during the appraisal and who commented on the draft ERG report. They would also like to thank Karen Welch, Information Scientist, SHTAC, for appraising the literature search strategies in the company’s submission, running updates of the company’s clinical-effectiveness searches and searching for ongoing studies; and Emma Loveman and Jill Colquitt, Senior Reviewers/Partners, Effective Evidence LLP, for providing feedback on the ERG report.

Author Contributions

All authors have commented on the submitted manuscript and have given their approval for the full version to be published. MR and JL summarised and critiqued the economic analysis submitted by the company. JS, KP, and PH summarised and critiqued the clinical-effectiveness evidence submitted by the company. MR drafted this manuscript and responded to feedback from all other authors. All authors reviewed, critiqued, and approved the final version submitted for publication. This summary has not been externally reviewed by PharmacoEconomics.

Compliance with Ethical Standards

Funding

This project was funded by the National Institute for Health Research (NIHR) HTA Program (project number 16/10/01 STA) [see the NIHR Journals Library website for further information—https://www.journalslibrary.nihr.ac.uk/#/]. The views and opinions expressed herein are the authors and do not necessarily reflect those of the HTA Programme, NICE, NIHR, NHS, or the Department of Health. Any errors are the responsibility of the authors. This summary of the ERG report was compiled after NICE issued the Final Appraisal Determination.

Conflict of interest

Micah Rose, Jonathan Shepherd, Petra Harris, Karen Pickett and Joanne Lord declare no conflicts of interest.

References

  1. 1.
    National Institute for Health and Care Excellence. Etelcalcetide for treating secondary hyperparathyroidism: technology appraisal guidance [TA448]. 2017. Available at: https://www.nice.org.uk/guidance/ta448. Accessed 27 Mar 2018.
  2. 2.
    Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pathogenesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol. 2011;6:913.CrossRefGoogle Scholar
  3. 3.
    Arbor Research Collaborative for Health. 2012 Annual Report of the Dialysis Outcomes and Practice Patterns Study: Hemodialysis Data 1997–2011. 2012. Available at: http://www.dopps.org/AnnualReport/.
  4. 4.
    Hedgeman E, Lipworth L, Lowe K, Saran R, Do T, Fryzek J. International burden of chronic kidney disease and secondary hyperparathyroidism: a systematic review of the literature and available data. Int J Nephrol. 2015;2015:184321.CrossRefGoogle Scholar
  5. 5.
    Caskey F, Cullen R. UK Renal Registry 18th Annual Report 2015. Nephron. 2016;132(Suppl 1):1–8.PubMedGoogle Scholar
  6. 6.
    National Institute for Health and Care Excellence. Cinacalcet for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease on maintenance dialysis therapy. Technology appraisal guidance [TA117]. 2007. Available at: https://www.nice.org.uk/guidance/ta117. Accessed 27 Mar 2018.
  7. 7.
    Kidney Disease: Improving Global Outcomes. KDIGO Clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int. 2009;76(Suppl 113):S1–130.Google Scholar
  8. 8.
    Block GA, Bushinsky DA, Cunningham J, Drueke TB, Ketteler M, Kewalramani R, et al. Effect of etelcalcetide vs placebo on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: two randomized clinical trials. JAMA. 2017;317(2):146–55.CrossRefGoogle Scholar
  9. 9.
    Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, et al. Effect of etelcalcetide vs cinacalcet on serum parathyroid hormone in patients receiving hemodialysis with secondary hyperparathyroidism: a randomized clinical trial. JAMA. 2017;317(2):156–64.CrossRefGoogle Scholar
  10. 10.
    Bushinsky D, Block G, Cheng S, Deng H, Ureña-Torres P, Vervloet M, et al. One year efficacy and safety of intravenous etelcalcetide (amg 416) in patients on hemodialysis with secondary hyperparathyroidism (Study 20120231). In: 53rd ERA-EDTA Congress: 21–24 May 2016, Vienna.Google Scholar
  11. 11.
    Amgen data on file. Study 20130213 Interim analysis summary 2016.Google Scholar
  12. 12.
    Liss K, Block G, Chertow GM, Dehmel B, Sun Y, Spiegel DM. Initiation of AMG 416 (etelcalcetide) after discontinuation of cinacalcet; TH-PO871. In: American Society of Nephrology; 3–8 Nov 2015: San Diego.Google Scholar
  13. 13.
    Garside R, Pitt M, Anderson R, Mealing S, Roome C, Snaith A, et al. The effectiveness and cost-effectiveness of cinacalcet for secondary hyperparathyroidism in end-stage renal disease patients on dialysis: a systematic review and economic evaluation. Health Technol Assess. 2007;11(18):iii, xi–xiii.Google Scholar
  14. 14.
    Belozeroff V, Chertow GM, Graham CN, Dehmel B, Parfrey PS, Briggs AH. Economic evaluation of cinacalcet in the united states: the EVOLVE trial. Value Health. 2015;18(8):1079–87.CrossRefGoogle Scholar
  15. 15.
    Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Goodman WG, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367(26):2482–94.CrossRefGoogle Scholar
  16. 16.
    Eandi M, Pradelli L, Iannazzo S, Chiroli S, Pontoriero G. Economic evaluation of cinacalcet in the treatment of secondary hyperparathyroidism in Italy. Pharmacoeconomics. 2010;28(11):1041–54.CrossRefGoogle Scholar
  17. 17.
    Briggs AH, Parfrey PS, Khan N, Tseng S, Dehmel B, Kubo Y, et al. Analyzing health-related quality of life in the EVOLVE trial: the joint impact of treatment and clinical events. Med Decis Mak. 2016;36(8):965–72.CrossRefGoogle Scholar
  18. 18.
    Pockett RD, Cevro E, Chamberlain G, Scott-Coombes D, Baboolal K. Assessment of resource use and costs associated with parathyroidectomy for secondary hyperparathyroidism in end stage renal disease in the UK. J Med Econ. 2014;17(3):198–206.CrossRefGoogle Scholar
  19. 19.
    Latimer NR, Abrams KR. NICE DSU Technical Support Document 16: Adjusting survival time estimates in the presence of treatment switching. 2014. Available at: http://nicedsu.org.uk/technical-support-documents/treatment-switching-tsd/. Accessed 27 Mar 2018.

Copyright information

© Crown 2018

Authors and Affiliations

  1. 1.Southampton Health Technology Assessments Centre (SHTAC)University of SouthamptonSouthamptonUK

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