Skip to main content
Log in

Budget Impact Analysis of Biosimilar Trastuzumab for the Treatment of Breast Cancer in Croatia

  • Original Research Article
  • Published:
Applied Health Economics and Health Policy Aims and scope Submit manuscript

Abstract

Background and Objective

Breast cancer is the most common cancer in women and has considerable impact on healthcare budgets and patients’ quality of life. Trastuzumab (Herceptin®) is a monoclonal antibody directed against the human epidermal growth factor receptor (HER2) for the treatment of breast cancer. Several trastuzumab biosimilars are currently in development. In 2015, trastuzumab was the drug with the highest financial consumption among all drugs in Croatia. This model estimates the 1-year budget impact of the introduction of biosimilar trastuzumab in Croatia.

Methods

A budget impact model, based on approvals for trastuzumab treatment in 2015, was developed for the introduction of biosimilars. Two biosimilar scenarios were developed: biosimilar scenario 1, based on all approvals in 2015, and biosimilar scenario 2, based on approvals after February 2015 and the reimbursement of the subcutaneous formulation of trastuzumab in Croatia. Only trastuzumab-naïve patients and drug-acquisition costs were used in the model. Uptake of biosimilar was assumed at 50 %. Scenarios were calculated with price discounts of 15, 25 and 35 %. The robustness of the model was tested by extensive sensitivity analyses.

Results

The projected drug cost savings from the introduction of biosimilar trastuzumab range from €0.26 million (scenario 2, 15 % price discount) to €0.69 million (scenario 1, 35 % price discount). If budget savings were reinvested to treat additional patients with trastuzumab, 14 (scenario 2, 15 % price discount) to 47 (scenario 1, 35 % price discount) additional patients could be treated. Sensitivity analyses showed that the incidence of breast cancer had the highest impact on the model, with a 10 % decrease in incidence leading to an 11.3 % decrease in projected savings.

Conclusion

The introduction of biosimilar trastuzumab could lead to significant drug cost savings in Croatia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86. doi:10.1002/ijc.29210.

    Article  CAS  PubMed  Google Scholar 

  2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, Rosso S, Coebergh JW, Comber H, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49(6):1374–403. doi:10.1016/j.ejca.2012.12.027.

    Article  CAS  PubMed  Google Scholar 

  3. Croatian Institute of Public Health: Izvješće o umrlim osobama u Hrvatskoj u 2014. godini. 2015. http://www.hzjz.hr/wp-content/uploads/2013/11/umrli_20141.pdf. Accessed 25 Jan 2015.

  4. Luengo-Fernandez R, Leal J, Gray A, Sullivan R. Economic burden of cancer across the European Union: a population-based cost analysis. Lancet Oncol. 2013;14(12):1165–74. doi:10.1016/S1470-2045(13)70442-X.

    Article  PubMed  Google Scholar 

  5. Zheng Z, Yabroff KR, Guy GP Jr, Han X, Li C, Banegas MP, et al. Annual medical expenditure and productivity loss among colorectal, female breast, and prostate cancer survivors in the United States. J Natl Cancer Inst. 2016;. doi:10.1093/jnci/djv382.

    Google Scholar 

  6. Ekwueme DU, Guy GP Jr, Rim SH, White A, Hall IJ, Fairley TL, et al. Health and economic impact of breast cancer mortality in young women, 1970-2008. Am J Prev Med. 2014;46(1):71–9. doi:10.1016/j.amepre.2013.08.016.

    Article  PubMed  Google Scholar 

  7. Ahmad S, Fergus K, McCarthy M. Psychosocial issues experienced by young women with breast cancer: the minority group with the majority of need. Curr Opin Support Palliat Care. 2015;9(3):271–8. doi:10.1097/SPC.0000000000000162.

    Article  PubMed  Google Scholar 

  8. Nahta R, Yu D, Hung MC, Hortobagyi GN, Esteva FJ. Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer. Nat Clin Pract Oncol. 2006;3(5):269–80. doi:10.1038/ncponc0509.

    Article  CAS  PubMed  Google Scholar 

  9. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177–82.

    Article  CAS  PubMed  Google Scholar 

  10. National Institute for Health and Clinical Excellence. Early and locally advanced breast cancer: diagnosis and treatment. NICE guidelines (CG80). 2009. https://www.nice.org.uk/guidance/cg80/resources/early-and-locally-advancedbreast-cancer-diagnosis-and-treatment-975682170565. Accessed 5 Jan 2016.

  11. National Institute for Health and Care Excellence. Guidance on the use of trastuzumab for the treatment of advanced breast cancer. NICE technology appraisal guidance (TA34). 2002. https://www.nice.org.uk/guidance/ta34/resources/guidance-on-the-use-of-trastuzumab-for-thetreatment-of-advanced-breast-cancer-2294516653765. Accessed 5 Jan 2016.

  12. European Medicines Agency. Herceptin authorisation details. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000278/human_med_000818.jsp&mid=WC0b01ac058001d124. Accessed 2 Jan 2016.

  13. Genentech. Highlights of prescribing information for Herceptin. Last revised in April 2015. http://www.gene.com/download/pdf/herceptin_prescribing.pdf. Accessed 2 Jan 2016.

  14. European Medicines Agency. Herceptin: EPAR—Product Information. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000278/WC500074922.pdf. Accessed 2 Jan 2016.

  15. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, Goldhirsch A, Untch M, Smith I, et al. Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005;353(16):1659–72. doi:10.1056/NEJMoa052306.

    Article  CAS  PubMed  Google Scholar 

  16. Slamon D, Eiermann W, Robert N, Pienkowski T, Martin M, Press M, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011;365(14):1273–83. doi:10.1056/NEJMoa0910383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92. doi:10.1056/NEJM200103153441101.

    Article  CAS  PubMed  Google Scholar 

  18. European Medicines Agency. CHMP assessment report. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000278/WC500153233.pdf. Accessed 2 Jan 2016.

  19. Ecker DM, Jones SD, Levine HL. The therapeutic monoclonal antibody market. MAbs. 2015;7(1):9–14. doi:10.4161/19420862.2015.989042.

    Article  CAS  PubMed  Google Scholar 

  20. Shaughnessy AF. Monoclonal antibodies: magic bullets with a hefty price tag. BMJ. 2012;345:e8346. doi:10.1136/bmj.e8346.

    Article  PubMed  Google Scholar 

  21. Jakovljevic M, Gutzwiller F, Schwenkglenks M, Milovanovic O, Rancic N, Varjacic M, et al. Costs differences among monoclonal antibodies-based first-line oncology cancer protocols for breast cancer, colorectal carcinoma and non-Hodgkin’s lymphoma. J BUON. 2014;19(4):1111–20.

    PubMed  Google Scholar 

  22. Li E, Subramanian J, Anderson S, Thomas D, McKinley J, Jacobs IA. Development of biosimilars in an era of oncologic drug shortages. Drug Des Devel Ther. 2015;9:3247–55. doi:10.2147/DDDT.S75219.

    Article  PubMed  PubMed Central  Google Scholar 

  23. European Medicines Agency. Guideline on similar biological medicinal products containing monoclonal antibodies—non-clinical and clinical issues. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128686.pdf. Accessed 15 Jan 2016.

  24. Food and Drug Administration. Information on biosimilars. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/. Accessed on 27 Jun 2016.

  25. European Medicines Agency. Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use. 2012. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128686.pdf. Accessed 15 Jan 2016.

  26. European Medicines Agency. Press release: European Medicines Agency recommends approval of first two monoclonal antibody biosimilars. 2013. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/06/WC500144941.pdf. Accessed 17 Jan 2016.

  27. Generics and Biosimilars Initiative. Biosimilars of trastuzumab. http://www.gabionline.net/Biosimilars/General/Biosimilars-of-trastuzumab. Accessed 16 Jan 2016.

  28. Thill M. New frontiers in oncology: biosimilar monoclonal antibodies for the treatment of breast cancer. Expert Rev Anticancer Ther. 2015;15(3):331–8. doi:10.1586/14737140.2015.993318.

    Article  CAS  PubMed  Google Scholar 

  29. Nelson KM, Gallagher PC. Biosimilars lining up to compete with Herceptin–opportunity knocks. Expert Opin Ther Pat. 2014;24(11):1149–53. doi:10.1517/13543776.2014.964683.

    Article  CAS  PubMed  Google Scholar 

  30. Celltrion. Celltrion’s Herzuma (trastuzumab) receives Korea MFDS approval. https://www.celltrion.com/en/pr/reportDetail.do?seq=324. Accessed 16 Jan 2016.

  31. Im Y-H, Odarchenko P, Grecea D, Komov D, Anatoliy CV, Gupta S, et al., editors. Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment. In: ASCO Annual Meeting Proceedings; 2013.

  32. Stanton, D.: Boos for Biocad’s biosimilars as Russia approves first Herceptin copy. BioPharma-Reporter.com. http://www.biopharma-reporter.com/Markets-Regulations/Russia-approves-its-first-Herceptin-biosimilar. Accessed 27 Feb 2016.

  33. Agency for Medicinal Products and Medical Devices of Croatia. Izvješće o prometu lijekova u Republici Hrvatskoj u 2015. http://halmed.hr/Novosti-i-edukacije/Publikacije-i-izvjesca/Izvjesca-o-potrosnji-lijekova/Izvjesce-o-potrosnji-lijekova-u-Republici-Hrvatskoj-u-2015/. Accessed 4 Oct 2016.

  34. Croatian Health Insurance Fund. Popis posebno skupih lijekova. 2016. http://cdn.hzzo.hr/wpcontent/uploads/2014/01/PSL-tablica-1-i-2_popis-za-NN_11_16.pdf. Accessed 4 Mar 2016.

  35. Voncina L, Strizrep T. Croatia: 2009/2010 pharmaceutical pricing and reimbursement reform. Eurohealth. 2011;16(4):20–2.

    Google Scholar 

  36. Croatian Institute of Public Health. Croatian National Cancer Registry 2013. 2015. http://www.hzjz.hr/wp-content/uploads/2013/11/Bilten-2013_final.pdf. Accessed 20 Jan 2016.

  37. Montserrat M, Leveque D, Barthelemy P, Bergerat JP. Duration of adjuvant trastuzumab treatment in routine practice. Anticancer Res. 2012;32(10):4585–8.

    CAS  PubMed  Google Scholar 

  38. Pivot X, Gligorov J, Muller V, Curigliano G, Knoop A, Verma S, et al. Patients’ preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study. Ann Oncol. 2014;25(10):1979–87. doi:10.1093/annonc/mdu364.

    Article  CAS  PubMed  Google Scholar 

  39. Ismael G, Hegg R, Muehlbauer S, Heinzmann D, Lum B, Kim SB, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol. 2012;13(9):869–78. doi:10.1016/S1470-2045(12)70329-7.

    Article  CAS  PubMed  Google Scholar 

  40. National Institute for Health and Clinical Excellence. Early and metastatic HER2-positive breast cancer: subcutaneous trastuzumab. Evidence summary: new medicine (ESNM13). 2013. https://www.nice.org.uk/guidance/esnm13/resources/early-and-metastatic-her2positive-breast-cancer-subcutaneous-trastuzumab-1502680801211845. Accessed 7 Jan 2016.

  41. Scottish Medicines Consortium: trastuzumab, 600 mg/5 ml solution for injection (Herceptin®). SMC No. (928/13). 2013. https://www.scottishmedicines.org.uk/files/advice/trastuzumab_Herceptin_FINAL_December_2013_for_website.pdf. Accessed 7 Jan 2016.

  42. Croatian Health Insurance Fund. Osnovna lista lijekova—u primjeni od 23.06.2016. http://www.hzzo.hr/zdravstveni-sustav-rh/trazilica-za-lijekove-s-vazecih-lista/. Accessed 27 Jun 2016.

  43. Ministry of Health. Pravilnik o mjerilima i načinu određivanja cijena lijekova na veliko i o načinu izvješćivanja o cijenama na veliko. National Gazette 83/2013. http://narodne-novine.nn.hr/default.aspx. Accessed 15 Jan 2016.

  44. Ministry of Health. Pravilnik o izmjenama Pravilnika o mjerilima i načinu određivanja cijena lijekova na veliko i o načinu izvješćivanja o cijenama na veliko. National Gazette 12/2014. http://narodne-novine.nn.hr/default.aspx. Accessed 15 Jan 2016.

  45. Ministry of Health: Pravilnik o izmjenama Pravilnika o mjerilima i načinu određivanja cijena lijekova na veliko i o načinu izvješćivanja o cijenama na veliko. National Gazette 69/2014. http://narodne-novine.nn.hr/default.aspx. Accessed 15 Jan 2016.

  46. The Croatian National Bank: godišnji i mjesečni prosjeci srednjih deviznih tečajeva Hrvatske narodne banke. http://old.hnb.hr/tecajn1/hstatistika-tecaja.htm. Accessed 20 Feb 2016.

  47. Godman B, Kwon H-Y, Brkičić LS, Bogut M, Sršen M, Tabain T et al. Pharmaceutical pricing in Croatia: a comparison of ordinances in 2013 versus 2009 and their potential savings to provide future guidance. Generics Biosimilars Initiat J (GaBI J). 2015;4(2):79–89. doi:10.5639/gabij.2015.0402.017.

    Article  Google Scholar 

  48. Brodszky V, Baji P, Balogh O, Pentek M. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries. Eur J Health Econ. 2014;15(Suppl 1):S65–71. doi:10.1007/s10198-014-0595-3.

    Article  PubMed  Google Scholar 

  49. Jha A, Upton A, Dunlop WC, Akehurst R. The budget impact of biosimilar infliximab (Remsima(R)) for the treatment of autoimmune diseases in five European countries. Adv Ther. 2015;32(8):742–56. doi:10.1007/s12325-015-0233-1.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Cortes J, Curigliano G, Dieras V. Expert perspectives on biosimilar monoclonal antibodies in breast cancer. Breast Cancer Res Treat. 2014;144(2):233–9. doi:10.1007/s10549-014-2879-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. European Medicines Agency. Questions and answers on biosimilar medicines (similar biological medicinal products). 2012. http://www.ema.europa.eu/docs/en_GB/document_library/Medicine_QA/2009/12/WC500020062.pdf. Accessed 8 Mar 2016.

  52. European Commission. What you need to know about biosimilar medicinal products. 2013. http://ec.europa.eu/DocsRoom/documents/8242/attachments/1/translations/en/renditions/native. Accessed 15 Jan 2016.

  53. Roche: Media Release. 2 September 2013.http://www.roche.com/med-cor-2013-09-02-e.pdf. Accessed 5 Mar 2016.

  54. Jackisch C, Kim SB, Semiglazov V, Melichar B, Pivot X, Hillenbach C, et al. Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study. Ann Oncol. 2015;26(2):320–5. doi:10.1093/annonc/mdu524.

    Article  CAS  PubMed  Google Scholar 

  55. Young KE, Remuzat C, Urbinati D, Toumi M. Boosting biosimilars uptake in European countries. Value Health. 2014;17(7):A408–9. doi:10.1016/j.jval.2014.08.958.

    Article  CAS  PubMed  Google Scholar 

  56. Mendoza C, Ionescu D, Radiere G, Remuzat C, Young KE, Toumi M. Biosimilar substitution policies: an overview. Value Health. 2015;18(7):A525. doi:10.1016/j.jval.2015.09.1616.

    Article  CAS  PubMed  Google Scholar 

  57. Stanton, D.: Biosimilar discounts and switching will wipe-out J&J’s Remicade in Norway, says regulator. BioPharma-Reporter.com. http://www.biopharma-reporter.com/Markets-Regulations/Biosimilar-discounts-will-wipe-out-Janssen-s-Remicade-sales-in-Norway. Accessed 28 Jun 2016.

  58. Mack A. Norway, biosimilars in different funding systems. What works. 2015:90-2.

  59. Yin D, Barker KB, Li R, Meng X, Reich SD, Ricart AD, et al. A randomized phase 1 pharmacokinetic trial comparing the potential biosimilar PF-05280014 with trastuzumab in healthy volunteers (REFLECTIONS B327-01). Br J Clin Pharmacol. 2014;78(6):1281–90. doi:10.1111/bcp.12464.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. PMLiVE. Top 50 pharmaceutical products by global sales. http://www.pmlive.com/top_pharma_list/Top_50_pharmaceutical_products_by_global_sales. Accessed 26 Feb 2016.

  61. Taylor, L: Breast cancer drug sales will almost double by 2023, says. IMS. PharmaTimes Media Limited. http://www.pharmatimes.com/Article/14-10-02/Breast_cancer_drug_sales_will_almost_double_by_2023_says_IMS.aspx. Accessed 26 Feb 2016.

  62. Lammers P, Criscitiello C, Curigliano G, Jacobs I. Barriers to the use of trastuzumab for HER2+ breast cancer and the potential impact of biosimilars: a physician survey in the United States and emerging markets. Pharmaceuticals 2014;7(9):943–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We would like to thank the Croatian Health Insurance Fund for providing the data to build this budget impact analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert Likić.

Ethics declarations

This study received no funding.

Conflict of interest

Authors August Cesarec and Robert Likić declare that they have no conflict of interest.

Author contributions

August Cesarec analysed input data, developed and ran the model and interpreted the results. Robert Likić assisted in the conception and the development of the model. Both authors were involved in drafting and revision of the manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cesarec, A., Likić, R. Budget Impact Analysis of Biosimilar Trastuzumab for the Treatment of Breast Cancer in Croatia. Appl Health Econ Health Policy 15, 277–286 (2017). https://doi.org/10.1007/s40258-016-0285-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40258-016-0285-7

Keywords

Navigation