Can local policies on biosimilars optimize the use of freed resources – experiences from Italy

Author byline as per print journal: Brian Godman1,2,3, BSc, PhD; Eleonora Allocati4, BSc, MSc; Evelien Moorkens5, MSc, PhD; Hye-Young Kwon, PhD1,6

Abstract:
There is an increasing need to prescribe biosimilars to fund new medicines and increasing medicine volumes. Bertolani and Jommi document successful measures introduced regionally in Italy.

The recent GaBI Journal manuscript by Bertolani and Jommi comprehensively assessed the implications of a range of policies including education, benchmarking and financial incentives, implemented by the different healthcare organisations (HCOs) among the regions in Italy to increase the use of biosimilars as a way to conserve resources. This included both prospective and retrospective analyses of shifts in prescribing behaviour among the different regions and potential savings generated as well as how the savings generated were used [1].

We linked the findings of the Bertolani and Jommi paper [1] with other recent studies in an attempt to stimulate ongoing debate regarding potential ways to enhance the future use of biosimilars as well as how best to utilize the considerable resource savings produced [2, 3] without compromising care.

The Bertolani and Jommi study is seen as particularly important as a source of information that can be used to provide future guidance as there have only been a limited number of studies to date that assessed differences in regional policies to enhance the prescribing of biosimilars in the ambulatory care setting where biologicals are increasingly being used [4]. A response rate of 38% to the survey is seen as acceptable [5, 6], especially since the regions surveyed covered 93% of the Italian population [1].

The need to leverage competition from biosimilars will only increase since without a major increase in the use of biosimilars global expenditure on medicines is projected to reach US$1.5 trillion by 2023 [79]. This growth will be primarily driven by increased expenditures on specialty biological medicines, including new medicines for chronic, complex, or rare diseases, such as cancer and orphan diseases. Global expenditure for these medicines is likely to reach 50% of total medicine expenditures in the near future [7, 10]. Such expenditures are difficult to sustain, especially in countries with universal healthcare systems that need to fund a growth in the use of medicines driven by increasing rates of non-communicable diseases, changes in clinical practice, and the continual launch of new, high-priced medicines that address areas of unmet need [1114]. There are additional concerns raised about some new, high-priced medicines for cancer and orphan diseases, for which funding appears driven more by the emotive nature of these diseases than by their proven clinical benefits [1518]. Their value is being increasingly questioned as more medicines advocated in guidelines become available as low cost, multi-sourced medicines or biosimilars [1921].

Biological medicines under increasing scrutiny include Humira® with global sales of US$19.9 billion in 2018. Although Humira® sales are now being decreased, especially in Europe, through increasing use of lower priced biosimilars as well as by the fact that AbbVie lowered the price of Humira® to compete [2226]. For example, among Danish hospitals, expenditures for adalimumab decreased by 82.8% following the availability of biosimilars with almost total replacement by biosimilars (95.1% utilization). In the UK, expenditure on adalimumab is envisaged to fall by 75% following the availability of biosimilars [23, 25]. Such reductions are welcomed, especially among lower- and middle-income countries, including Central and Eastern European countries, where the use of biologicals has been limited by available governmental resources as well as by high patient co-payments [2729]. Biosimilar switching programmes have been shown to conserve resources by a number of studies that also were unable to demonstrate meaningful differences in effectiveness or safety between biosimilars and originators. Such studies have included infliximab and other biologicals across a range of indications [3038]. There have, however, been some concerns requiring patient monitoring [39, 40]. Such concerns could be exacerbated by multiple modifications in the manufacturing of originator biological drugs that can occur without companies being required to undertake clinical studies to assess the effect of such changes on clinical outcomes in actual practice, even with major manufacturing changes [41, 42].

Other biological medicines of special interest to health authorities across Europe and beyond include rituximab, infliximab and etanercept with current global sales of US$7.9 billion, US$5.9 billion and US$ 5.8 billion in 2017, respectively [4345]. These concerns persist despite the fact that these sales are being reduced as the result of the increasing use of lower cost biosimilars [38, 39, 45-49]. Global sales of Herceptin® (trastuzumab) were stable in 2019 at US$7 billion due to increasing use of biosimilar trastuzumab. The use of biosimilar trastuzumab is expected to continue to increase globally. Trastuzumab biosimilars have already captured 45% of the European market [5052]. However, these savings are being offset by growing expenditures on pertuzumab in combination with trastuzumab; with annual sales of US$2.8 billion in 2019 as well as by the use of Kadcyla® (trastuzumab emtansine), which is expected to reach annual sales of US$4.94 billion by 2023 [50, 53].

Another important biological is long ­acting insulin glargine used for patients with Type 1 diabetes. The insulin glargine market was valued at approximately US$3.88 billion in 2018; and is envisaged to reach US$9.26 billion by 2025 [54]. However, potential savings associated with the introduction of biosimilar insulin glargine have been hampered by the limited price reductions seen in practice in a number of countries. There are also concerns with switching because differences in devices between manufacturers could increase the rate of hypoglycaemia [5558]. These concerns have resulted in some health authorities advising against switching, despite similar effectiveness and safety being demonstrated in studies comparing the originator and a biosimilar [55, 56, 59-62]. The situation is however changing, at least in the US where a biosimilar insulin glargine reached over 40% of market share in the US Medicaid programme in 2018. There are also a number of initiatives and publications pushing for increased use of biosimilars among European countries including those encouraging new patients to be started on a biosimilar [49, 63-66].

A number of published studies have shown the potential for considerable savings from biosimilars. These results are pushing health authorities to employ initiatives to enhance their use [3, 9, 38, 49, 51, 67-70]. Winegarden (2019) in the US estimated annual savings of up to US$7 billion from the use of a range of biosimilars, and that these savings are likely to grow as more biosimilars become available [3]. However, for maximum savings, both supply- and demand-side measures are needed [21, 69]. This has been shown in studies of oral generic medicines comparing potential policies and savings in Korea with those in the UK [7174]. Multiple demand- and supply-side measures in Scotland resulted in a considerable reduction in expenditure on lipid lowering medicines and proton pump inhibitors despite appreciably increased volumes [73, 74]. Moorkens et al. (2017), Rémuzat et al. (2017) and Vogler et al. (2017) have all recently summarized ongoing demand-side measures in Europe to enhance the use of biosimilars. Simoens et al. (2018) also provided guidance on additional demand-side measures that could be introduced to further realize the benefits of biosimilars [7578]. There are European countries where some lower-cost biosimilars now account for the total market, e.g. erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) [79], and countries such as France and the UK are actively working to increase biosimilar penetration rates [80, 81].

Brill in the US has recently discussed the benefits of shared savings to enhance biosimilar use among State Medicaid programmes [10]. Siu et al. (2019) documented ongoing activities to enhance the use of biosimilars in both the private and ­public sectors in Canada [70]. These activities include preferential coverage by private insurers for increasing use of biosimilars, the pan-Canadian Oncology Biosimilars Initiative to enhance adoption of biosimilars in oncology (an attempt to address concerns with funding in oncology), as well as the British Columbia Biosimilars Initiative in May 2019 that promotes switching, with the savings used to lower premiums and co-pays where pertinent [70]. In addition, Biosimilars Canada has recently developed a centralized patient support service platform to assist manufacturers and patients with increasing the use of biosimilars [70]. Such activities are needed to promote the use of biosimilars because originator manufacturers have been appreciably lowering prices of their originators just before patent expiry to dissuade biosimilar companies from entering the market [22, 44, 79]. Suggestions have been made that originator companies should automatically lower their prices following patent expiry, thereby negating the need for biosimilars to interfere with the market in the first place [82]. Methods are needed to counter other behaviours of originator companies such as developing new formulations just before patent expiry to create a barrier to biosimilars mirroring other evergreening tactics [79, 83].

It was impressive to see that 89% of HCO surveyed by Bertolani and Jommi had implemented policies to enhance the use of biosimilars [1]. Educational activities were particularly prominent, increasing in recent years, including information on market access pathways for biosimilars as well as the results of tenders. Educational activities are crucial to allay fears regarding the effectiveness and safety of biosimilars. These fears are illustrated in Italy by the seven scientific Italian societies that recently expressed concerns about the Regional Administrative Court of Piemonte promoting the automatic substitution of biologicals in terms of therapeutic continuity for patients and concerns with the freedom of prescribing clinicians [84]. Despite this, benchmarking of biosimilar prescribing among physicians was already taking place among 75% of HCOs surveyed and this is likely to grow since such benchmarking of physician prescribing is working well in other countries [1, 85]. The 62% of HCOs that also provided physicians with prescribing targets for biosimilars is similar to what has been seen in other countries and regions [8688], with 68% and 24% respectively, introducing incentives and sanctions to improve prescribing rates. Sanctions include monetary sanctions and potentially removal of the right to prescribe [1].

A concern though is that patients were involved in educational/information programmes among only 22% of the HCOs surveyed [1]. This is a potentially important weakness since all key stakeholders need to be convinced about the value of biosimilars in order to reduce any potential nocebo effects [89, 90].

The study of Bertolani and Jommi adds to a number of examples of successful multiple demand-side measures including preferentially encouraging the prescribing of multi-sourced medicines versus originators and patented medicines in a class without compromising care [9193]. Monies saved can subsequently be used to fund new more expensive medicines as well as other healthcare services such as diagnostics. Ninety-three per cent of HCOs also provided physicians with information retrospectively or prospectively on potential savings from increased use of biosimilars, with 25% of HCOs also participating in post-marketing studies to help further fears with biosimilars [1]. However, only 21% of HCOs systematically estimated the proportion of potential patients not receiving biosimilars, with only rare perceptual surveys among patients and other healthcare professionals. This situation may need to change given the stated concerns of the seven scientific Italian societies [84].

In conclusion, Bertolani and Jommi, have provided a comprehensive review of ongoing policies among HCOs in the different regions of Italy and their potential to influence on future directions. This information is useful for other countries where demand-side measures can be localised to meet future goals, with the potential for localities to learn from each other. This is important to stimulate increasing use of biosimilars in a way that addresses the accelerating resource challenges brought about by the expanding use of medicines in ageing populations as well as the need to pay for new, high-priced medicines that address areas of previously poorly or untreatable diseases.

Funding sources

There was no funding for this paper.

Competing interests: The authors have no conflicts of interest to declare.

Provenance and peer review: Commissioned; internally peer reviewed.

Authors

Brian Godman1,2,3, BSc, PhD
Eleonora Allocati4, BSc, MSc
Evelien Moorkens5, MSc, PhD
Hye-Young Kwon, PhD1,6

1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
2Division of Public Health Pharmacy and Management, School of Pharmacy, Faculty of Health Sciences, Sefako Makgatho Health Sciences University, Pretoria, South Africa
3Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden
4Istituto di Ricerche Farmacologiche ‘Mario Negri’ IRCCS, Milan, Italy
5KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium
6College of Pharmacy, Seoul National University, Seoul, Korea

References
1. Bertolani A, Jommi C. Local policies on biosimi­lars: are they designed to optimize use of freed resources? Generics and Biosimilars Journal (GaBI Journal). 2020;9(4):163-70. doi:10.5639/gabij.2020.0904.027
2. Pettit C. Biosimilars market is ripe for cost savings. Am J Manag Care. 2019.
3. Winegarden W. The biosimilar opportunity: a state breakdown. Pacific Research Institute Publication. 2019.
4. Moorkens E, Simoens S, Troein P, Declerck P, Vulto AG, Huys I. Different policy measures and practices between Swedish counties influence market dynamics: Part 2-Biosimilar and originator etanercept in the outpatient setting. Biodrugs: 2019;33(3):299-306.
5. Pandya C. What is an acceptable response rate for online surveys? AppJetty. 2019.
6. Lindemann N. What’s the average survey response rate? [2019 benchmark]. 2019. Available from: https://surveyanyplace.com/average-survey-response-rate/
7. IQVIA. The global use of medicine in 2019 and outlook to 2023. Forecasts and areas to watch. 2019 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/the-global-use-of-medicine-in-2019-and-outlook-to-2023
8. Inotai A, Csanádi M, Vitezic D, Francetic I, Tesar T, et al. Policy practices to maximise social benefit from biosimilars. J Bioequiv Availab. 2017;9:467-72.
9. Povero M, Pradelli L. Funding innovation thanks to anti-TNF-a biosimilars uptake: the economic impact in Italy. Farmeconomia. Health economics and therapeutic pathways. 2020;21(1):37-47.
10. Brill A. Shared savings demonstration for biosimilars in medicare: an opportunity to promote biologic drug competition. 2020. Matrix Global Advisors.
11. Morgan SG, Bathula HS, Moon S. Pricing of pharmaceuticals is becoming a major challenge for health systems. BMJ. 2020;368:l4627-l.
12. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
13. Gyasi RM, Phillips DR. Aging and the rising burden of noncommunicable diseases in Sub-Saharan Africa and other low- and middle-income countries: a call for holistic action. Gerontologist. 2020;60(5):806-11.
14. Godman B, Bucsics A, Vella Bonanno P, Oortwijn W, Rothe CC, Ferrario A, et al. Barriers for access to new medicines: searching for the balance between rising costs and limited budgets. Front Public Health. 2018;6:328.
15. Cohen D. Cancer drugs: high price, uncertain value. BMJ. 2017;359:j4543.
16. Luzzatto L, Hyry HI, Schieppati A, Costa E, Simoens S, Schaefer F, et al. Outrageous prices of orphan drugs: a call for collaboration. Lancet. 2018;392(10149):791-4.
17. Godman B, Wild C, Haycox A. Patent expiry and costs for anticancer medicines for clinical use. Generics and Biosimilars Initiative Journal (GaBI Journal). 2017;6(3):105-6. doi:10.5639/gabij.2017.0603.021
18. Haycox A. Why cancer? Pharmacoeconomics. 2016;34(7):625-7.
19. Godman B, Hill A, Simoens S, Kurdi A, Gulbinovič J, Martin AP, et al. Pricing of oral generic cancer medicines in 25 European countries; findings and implications. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;8(2):49-70. doi:10.5639/gabij.2019.0802.007
20. Derbyshire M, Shina S. Patent expiry dates for biologicals: 2017 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(1):29-34. doi:10.5639/gabij.2019.0801.003
21. Dutta B, Huys I, Vulto AG, Simoens S. Identifying key benefits in European off-patent biologics and biosimilar markets: it is not only about price! BioDrugs. 2020;34(2):159-70.
22. Sagonowsky E. AbbVie’s massive Humira discounts are stifling Netherlands biosimilars: report. Fierce Pharma. 2019 Apr 2.
23. Jensen TB, Kim SC, Jimenez-Solem E, Bartels D, Christensen HR, Andersen JT. Shift from adalimumab originator to biosimilars in Denmark. JAMA Intern Med. 2020;180(6):902-3.
24. Stanton D. Global Humira sales near $20bn, but expect decline in 2019. BioProcess International. 2019 Jan 28.
25. Davio K. After biosimilar deals, UK spending on adalimumab will drop by 75%. Center for Biosimilars. 2018 Nov 26.
26. Davio K. Researchers predict substantial savings for Europe on the strength of biosimilar adalimumab. Center for Biosimilars. 2019 May 21.
27. Baumgart DC, Misery L, Naeyaert S, Taylor PC. Biological therapies in immune-mediated inflammatory diseases: can biosimilars reduce access inequities? Front Pharmacol. 2019;10:279.
28. Kostic M, Djakovic L, Šujić R, Godman B, Jankovic SM. Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis): cost of treatment in Serbia and the implications. Appl Health Econ Health Policy. 2017;15(1):85-93.
29. Putrik P, Ramiro S, Kvien TK, Sokka T, Pavlova M, Uhlig T, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis. 2014;73(1):198-206.
30. Jørgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304-16.
31. Høivik ML, Buer LCT, Cvancarova M, Warren DJ, Bolstad N, Moum BA, et al. Switching from originator to biosimilar infliximab – real world data of a prospective 18 months follow-up of a single-centre IBD population. Scand J Gastroenterol. 2018;53(6):692-9.
32. Milassin Á, Fábián A, Molnár T. Switching from infliximab to biosimilar in inflammatory bowel disease: overview of the literature and perspective. Therap Adv Gastroenterol. 2019;12:1756284819842748.
33. Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. Drugs. 2018;78(4):463-78.
34. Gisondi P, Bianchi L, Calzavara-Pinton P, Conti A, Chiricozzi A, Fimiani M, et al. Etanercept biosimilar SB4 in the treatment of chronic plaque psoriasis: data from the Psobiosimilars registry. Br J Dermatol. 2019;180(2):409-10.
35. Stebbing J, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, et al. Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC). J Clin Oncol. 2017;35(15_suppl):510.
36. Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019;120(2):172-82.
37. Tweehuysen L, Huiskes VJB, van den Bemt BJF, Vriezekolk JE, Teerenstra S, van den Hoogen FHJ, et al. Open-label, non-mandatory transitioning from originator etanercept to biosimilar SB4: six-month results from a controlled cohort study. Arthritis Rheumatol. 2018;70(9):1408-18.
38. Chan A, Kitchen J, Scott A, Pollock D, Marshall R, Herdman L. Implementing and delivering a successful biosimilar switch programme – the Berkshire West experience. Future Healthc J. 2019;6(2):143-5.
39. Nisar MK. 292 Switching to biosimilar rituximab: a real world study. Rheumatology. 2018;57(suppl_3).
40. Ratnakumaran R, To N, Gracie DJ, Selinger CP, O’Connor A, Clark T, et al. Efficacy and tolerability of initiating, or switching to, infliximab biosimilar CT-P13 in inflammatory bowel disease (IBD): a large single-centre experience. Scand J Gastroenterol. 2018;53(6):700-7.
41. Jiménez-Pichardo L, Gázquez-Perez R, Sierra-Sánchez JF. Degree of prescriber’s knowledge about variability in biological drugs “innovators” in manufacturing process. Eur J Clin Pharmacol. 2018;74(4):505-11.
42. Vezér B, Buzás Z, Sebeszta M, Zrubka Z. Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents. Curr Med Res Opin. 2016;32(5):829-34.
43. Global tumor necrosis factor inhibitors drug ­market, dosage, price & clinical pipeline outlook 2024. PRNewswire. 2018 Mar 16.
44. Hoen E’t. Humiragate: AbbVie’s desperate attempts to keep its monopoly. Medicines Law & Policy. 2019.
45. Davio K. Roche’s European rituximab sales drop 11% due to biosimilar competition. Center for Biosimilars. 2018 Feb 5.
46. Davio K. Biosimilar competition leads to 9.7% drop in Remicade sales for Johnson & Johnson. Center for Biosimilars. 2018 Jan 23.
47. Matusewicz W, Godman B, Pedersen HB, Fürst J, Gulbinovič J, Mack A, et al. Improving the managed introduction of new medicines: sharing experiences to aid authorities across Europe. Exp Rev Pharmacoecon Outcomes Res. 2015;15(5):755-8.
48. Småstuen MC, Madla R, Solli O, Hjelvin E. OP0311 retrospective analysis of prescription dynamics of etanercept after introduction of biosimilars based on Norwegian prescription database. An interim analysis. Ann Rheumatic Dis. 2019;78:237-8.
49. Mansell K, Bhimji H, Eurich D, Mansell H. Potential cost-savings from the use of the biosimilars filgrastim, infliximab and insulin glargine in Canada: a retrospective analysis. BMC Health Serv Res. 2019;19(1):827.
50. Taylor P. Roche’s Herceptin/Perjeta fixed-dose combo filed with FDA. PMLive. 2020 Feb 25.
51. Lee SM, Jung JH, Suh D, Jung YS, Yoo SL, Kim DW, et al. Budget impact of switching to biosimilar trastuzumab (CT-P6) for the treatment of breast cancer and gastric cancer in 28 European countries. BioDrugs. 2019;33(4):423-36.
52. Jeremias S. Biosimilars gain market share and advocates get aboard. Center for Biosimilars. 2020 Aug 15.
53. GlobalData. PharmaPoint. Kadcyla (HER2-positive breast cancer) – forecast and market analysis to 2023. 2014 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.marketresearch.com/product/sample-8464560.pdf
54. Zion Market Research. Insulin glargine market: by type (pre-filled syringe and single dose vial), by application (type 1 diabetes and type 2 diabetes), by distribution channel (hospital pharmacy, online sales, retail pharmacy and other distribution channels): global industry perspective, comprehensive analysis and forecast, 2018–2025. 2019 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.zionmarketresearch.com/report/insulin-glargin-market
55. NHS Lothian. Lothian Formulary. 6.1.1 Insulins. 2020 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.ljf.scot.nhs.uk/LothianJointFormularies/Adult/6.0/6.1/6.1.1/Pages/default.aspx
56. Greater Glasgow and Clyde. Medicines Update – prescribing medicines by brand. 2020 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: http://www.ggcprescribing.org.uk/blog/prescribing-medicines-brand/
57. Aladul MI, Fitzpatrick RW, Chapman SR. Healthcare professionals’ perceptions and perspectives on biosimilar medicines and the barriers and facilitators to their prescribing in UK: a qualitative study. BMJ Open. 2018;8(11):e023603.
58. Greener M. Why isn’t the NHS making the most of biosimilar insulin? Prescriber August 2019: 21-4.
59. Heinemann L, Carter AW. Will biosimilar insulins be cheaper? Diabetes Technol Ther. 2017;19(9):513-5.
60. Yamada T, Kamata R, Ishinohachi K, Shojima N, Ananiadou S, Nom H, et al. Biosimilar vs originator insulins: systematic review and meta-analysis. Diabetes Obes Metab. 2018;20(7):1787-92.
61. Blevins TC, Barve A, Raiter Y, Aubonnet P, Athalye S, Sun B, et al. Efficacy and safety of MYL-1501D versus insulin glargine in people with type 1 diabetes mellitus: results of the INSTRIDE 3 phase 3 switch study. Diabetes Obes Metab. 2020;22(3):365-72.
62. Lamb YN, Syed YY. LY2963016 insulin glargine: a review in type 1 and 2 diabetes. BioDrugs. 2018;32(1):91-8.
63. Greater Glasgow and Clyde. Medicines Update – Semglee® – preferred brand of insulin glargine. 2020 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: http://ggcprescribing.org.uk/blog/alternatives-insulin-glargine-post-tc/
64. Saborido-Cansino C, Santos-Ramos B, Carmona-Saucedo C, Rodríguez-Romero MV, González-Martín A, Palma-Amaro A, et al. [Effectiveness of an intervention strategy in the biosimilar glargine prescription pattern in primary care]. Aten Primaria. 2019;51(6):350-8.
65. Agirrezabal I, Sánchez-Iriso E, Mandar K, Cabasés JM. Real-world budget impact of the adoption of insulin glargine biosimilars in primary care in England (2015-2018). Diabetes Care. 2020;43(8):1767-73.
66. Hernandez I, Good CB, Shrank WH, Gellad WF. Trends in Medicaid prices, market share, and spending on long-acting insulins, 2006-2018. Jama. 2019;321(16):1627-9.
67. González-Fernández M, Villamañán E, Jiménez-Nácher I, Moreno F, Plasencia C, Gaya F, et al. Cost evolution of biological agents for the treatment of spondyloarthritis in a tertiary hospital: influential factors in price. Int J Clin Pharm. 2018;40(6):1528-38.
68. Gulácsi L, Brodszky V, Baji P, Rencz F, Péntek M. The rituximab biosimilar CT-P10 in rheumatology and cancer: a budget impact analysis in 28 European countries. Adv Ther. 2017;34(5):1128-44.
69. Kim Y, Kwon HY, Godman B, Moorkens E, Simoens S, Bae S. Uptake of biosimilar infliximab in the UK, France, Japan, and Korea: budget savings or market expansion across countries? Front Pharmacol. 2020;11:970.
70. Siu ECK, Tomalin A, West K, Anderson S, Wyatt G. An ever-evolving landscape: an update on the rapidly changing regulation and reimbursement of biosimilars in Canada. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;8(3):107-18. doi:10.5639/gabij.2019.0803.014
71. Kwon HY, Godman B. Drug pricing in South Korea. Appl Health Econ Health Policy. 2017;15(4):447-53.
72. Kwon HY, Kim H, Godman B, Reich MR. The impact of South Korea’s new drug-pricing policy on market competition among off-patent drugs. Expert Rev Pharmacoecon Outcomes Res. 2015;15(6):1007-14.
73. Leporowski A, Godman B, Kurdi A, MacBride-Stewart S, Ryan M, Hurding S, et al. Ongoing activities to optimize the quality and efficiency of lipid-lowering agents in the Scottish national health service: influence and implications. Expert Rev Pharmacoecon Outcomes Res. 2018;18(6):655-66.
74. Godman B, Kurdi A, McCabe H, MacBride-Stewart S, Leporowski A, Hurding S et al. Ongoing activities to influence the prescribing of proton pump inhibitors within the Scottish National Health Service: their effect and implications. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(4):142-51. doi:10.5639/gabij.2018.0704.030
75. Simoens S, Le Pen C, Boone N, Breedveld N, Llombart-Cussac A, Jorgensen F, et al. How to realize the potential of off-patent biologicals and biosimilars in Europe? Guidance to policymakers. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(2):70-4. doi:10.5639/gabij.2018.0702.014
76. Moorkens E, Vulto AG, Huys I, Dylst P, Godman B, Keuerleber S, et al. Policies for biosimilar uptake in Europe: an overview. PloS One. 2017;12(12):e0190147.
77. Vogler S, Schneider P. Do pricing and usage-enhancing policies differ between biosimilars and generics? Findings from an international survey. Generics and Biosimilars Initiative Journal (GaBI Journal). 2017;6(2):79-88. doi:10.5639/gabij.2017.0602.015
78. Rémuzat C, Kapuśniak A, Caban A, Ionescu D, Radière G, Mendoza C, et al. Supply-side and demand-side policies for biosimilars: an overview in 10 European member states. J Mark Access Health Policy. 2017;5(1):1307315.
79. European Commission. IQVIA Report 2018: the impact of biosimilar competition in Europe [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://ec.europa.eu/docsroom/documents/31642
80. GaBI Online – Generics and Biosimilars Initiative. Quotas. France aims to reach 80% biosimilar penetration by 2022 [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2020 Sep 28]. Available from: www.gabionline.net/Policies-Legislation/France-aims-to-reach-80-biosimilar-penetration-by-2022
81. NHS England. Commissioning framework for biological medicines (including biosimilar medicines). 2017 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.england.nhs.uk/wp-content/uploads/2017/09/biosimilar-medicines-commissioning-framework.pdf
82. Atteberry P, Bach PB, Ohn JA, Trusheim M. Biologics are natural monopolies (Part 1): why biosimilars do not create effective competition. Health Affairs Blog. 2019. Available from: https://www.healthaffairs.org/do/10.1377/hblog20190405.396631/full/
83. Vernaz N, Haller G, Girardin F, Huttner B, Combescure C, Dayer P, et al. Patented drug extension strategies on healthcare spending: a cost-evaluation analysis. PLoS Med. 2013;10(6):e1001460.
84. Quotidiano Sanita. Oggetto: Sentenza 465/20 TAR Piemonte Sezione I sull’approvvigionamento di farmaci biologici. 14 September 2020 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: http://www.quotidianosanita.it/allegati/allegato628568.pdf
85. Gustafsson LL, Wettermark B, Godman B, Andersen-Karlsson E, Bergman U, Hasselstrom J, et al. The ‘wise list’ – a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm. Basic Clin Pharmacol Toxicol. 2011;108(4):224-33.
86. Godman B, Allocati E, Moorkens E. Ever-changing landscape of biosimilars in Canada; findings and implications from a global perspective. Generics and Biosimilars Initiatives (GaBI Journal). 2019;8(3):93-7. doi:10.5639/gabij.2019.0803.012
87. NHS Scotland. Secondary care national therapeutic indicators 2018/19 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: https://www.therapeutics.scot.nhs.uk/wp-content/uploads/2018/08/Secondary-Care-National-Therapeutic-Indicators-Version-1.0.pdf.
88. All Wales Medicine Strategy Group. National prescribing indicators 2018–2019. 2018 [homepage on the Internet]. [cited 2020 Sep 28]. Available from: http://www.awmsg.org/docs/awmsg/medman/National%20Prescribing%20Indicators%202018-2019.pdf.
89. Colloca L, Panaccione R, Murphy TK. The clinical implications of nocebo effects for biosimilar therapy. Front Pharmacol. 2019;10:1372.
90. Kristensen LE, Alten R, Puig L, Philipp S, Kvien TK, Mangues MA, et al. Non-pharmacological effects in switching medication: the nocebo effect in switching from originator to biosimilar agent. BioDrugs. 2018;32(5):397-404.
91. Godman B, Wettermark B, Bishop I, Burkhardt T, Fürst J, Garuoliene K, et al. European payer initiatives to reduce prescribing costs through use of generics.Generics and Biosimilars Initiative Journal (GaBI Journal). 2012;1(1):22-7. doi:10.5639/gabij.2012.0101.007
92. Godman B, Wettermark B, van Woerkom M, Fraeyman J, Alvarez-Madrazo S, Berg C, et al. Multiple policies to enhance prescribing efficiency for established medicines in Europe with a particular focus on demand-side measures: findings and future implications. Front Pharmacol. 2014;5:106.
93. Godman B, Shrank W, Andersen M, Berg C, Bishop I, Burkhardt T, et al. Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications. Expert Rev Pharmacoecon Outcomes Res. 2010;10(6):707-22.

Author for correspondence: Brian Godman, BSc, PhD; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, UK; Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, SE-14186 Stockholm, Sweden

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Ever-changing landscape of biosimilars in Canada; findings and implications from a global perspective

Author byline as per print journal: Brian Godman1,2,3, BSc, PhD; Eleonora Allocati4, BSc, MSc; Evelien Moorkens5, BSc, MSc

Abstract:
Siu et al. comprehensively assessed the rapidly changing regulation and reimbursement environment for biologicals and biosimilars in Canada and the resultant implications. The current situation in Canada is compared with similar initiatives across different countries to enhance savings from biosimilars to improve the affordability of biologicals.

Submitted: 9 September 2019; Revised: 12 September 2019; Accepted: 12 September 2019; Published online first: 25 September 2019

Brian Godman, Eleonora Allocati and Evelien Moorkens review the paper by Siu et al. regarding the evolving regulatory and reimbursement landscape in Canada [1], and subsequently link these within the broader global context of biosimilar market access to stimulate future activities and debates in this important area. This includes the current and potential market value of biosimilars, their regulatory and reimbursement environments as well as ongoing initiatives across countries to enhance their utilization to maximize potential savings. In addition, the potential sustainability of appreciable discounts among both originator and biosimilar manufacturers is discussed.

Siu et al. point out that biologicals are now commonly prescribed medicines for a wide variety of disease areas including diabetes, immunological diseases such as arthritis, inflammatory bowel disease and psoriasis, as well as for a number of cancers [14]. The high prices for new cancer medicines coupled with the growing prevalence of patients with cancer have resulted in growing (and now considerable) sales for oncology medicines across Europe and globally. Worldwide sales of cancer medicines, many of which are biologicals, was US$107 billion in 2015 and rising [5, 6]. The global anti-tumour necrosis factor (ant-TNF) market was valued at US$40.4 billion in 2017, and expected to expand at 2.54% per year with Europe and the US currently accounting for 87.70% of sales [7]. Within this, worldwide sales of adalimumab were US$17.6 billion in 2017, rising to nearly US$20 million in 2018 thereby making it the world’s best-selling medicine, with infliximab sales at US$5.9 billion in 2017 and etanercept at US$5.8 billion in 2017 [8, 9]. In Canada in 2017, biologicals accounted for 21.60% of overall public healthcare expenditure with the anti-TNF medicines accounting for 8.20% of total expenditure [1]. This compares with the US where biologicals currently account for 37% of net drug spending [10]. In the UK, anti-TNF medicines are also one of the highest spend areas within high-cost medicines, with GBP 780 million spent in England in 2018 [11], and in Germany, adalimumab was the top-selling medicine in 2017 with net costs to the statutory health insurance system of Euros 975 million [12]. Consequently, the introduction of biosimilars, especially in oncology and immunological diseases, should be of considerable interest to payers of health care and patients worldwide. We have seen limited use to date of biological medicines in many Central and Eastern European countries versus Western European countries due to their high costs and co-payments [1315]. Consequently, biosimilars should help address this as prices fall. A competitive market should also bring down the cost of biosimilar insulins, helping many patients in low- and middle-income countries currently denied such treatments [16].

As a result of the current and envisaged sales of biological medicines coupled with ongoing initiatives, we are seeing considerable growth in the availability and use of biosimilars especially in China and Europe [1720]. This will help increase their worldwide sales from approximately US$4 billion in 2018 [21]. Competition, with the resultant impact on overall expenditures, should intensify as many biological medicines that are currently used first- or second-line in treatment regimens lose their patent benefitting patients and payers [22].

Siu et al. point out appreciable changes in the regulatory and Health Technology Assessment (HTA) domains in the biosimilar environment in Canada in recent years to enhance their availability and promote their uptake [1]. This includes Health Canada in 2015 launching a pilot programme to provide manufacturers with the ability to discuss their biosimilar with Health Canada. In 2017, Health Canada laid out a Regulatory Review of Drugs and Devices which included a project to improve access to biologicals (biosimilars and non-biosimilars) by increasing their regulatory review capacity [1]. This should result in a more secure supply of biological drugs and more affordable biologicals. In addition, Health Canada and HTA organizations in Canada as well as the Institut national d’excellence en santé et en services sociaux (INESSS) in Quebec began collaborating in 2018 to better align review processes including biosimilars to reduce duplication and time lags between regulatory approval and reimbursement [1]. Heath Canada also intends to implement an updated naming convention for biologicals including the product’s brand name, International Nonproprietary Name (INN), and the Drug Identification Number (DIN), to support a clear distinction between biologicals including biosimilars to enhance adverse event tracking [1]. There have also been initiatives in other countries to enhance earlier access to biosimilars [20, 21, 2326] although further developments are being proposed [27]. Interestingly, whilst modifications to the manufacturing process of originator biological drugs are common, regulators have very rarely required clinical studies to assess similarities even in the case of major manufacturing changes [28, 29].

With respect to reimbursing biosimilars, a number of significant changes have taken place recently in Canada to ease the situation. In Canada, the CADTH (Canadian Agency for Drugs and Technologies in Health) Common Drug Review (CDR) plays an important role in deciding whether medicines will be eligible for public reimbursement, with the provinces subsequently typically making the final decision based on CDR recommendations [30]. In May 2019, CADTH announced that as of 1 June 2019, it would no longer routinely review biosimilars via its CDR and pCODR (pan-Canadian Oncology Drug Review) programmes to streamline access [1]. A similar situation is seen in Quebec with INESSS. The pan-Canadian Pharmaceutical Alliance (pCPA) subsequently uses its combined purchasing power to improve access and increase the cost-effectiveness of medicines, similar to cross country collaborations in Europe [3134]. In 2016, pCPA launched a more comprehensive biosimilar policy and in 2018 released a Biologics Policy Directive in which biological drugs for which biosimilars are already reimbursed as well as any new biosimilar will not be considered for reimbursement unless there are transparent price reductions to the lowest list price, providing an exemplar to others [1]. In addition, the potential for tiered pricing in certain therapeutic areas, which is likely to lead to increasing discounts as more biosimilars are launched. Manitoba was the first Canadian Province to instigate tiered arrangements in which biological-naïve patients must first be prescribed a biosimilar or an approved biological where no biosimilar exists [1]. Private insurers in Canada are also now offering preferential coverage for biosimilars leading to average savings of CA$8,500 per participating member per year [1]. Such initiatives should help boost the use of biosimilars in Canada along with educational, awareness and other initiatives, with biosimilar use currently lagging behind Europe [1, 19].

Biosimilars Canada has also recently developed a centralized patient support service platform to assist manufacturers and patients [1]. Policies regarding switching should also help enhance the use of biosimilars in Canada along with collecting real-world evidence to help ally current fears [1]. There have been considerable concerns with patients being switched between an originator biological medicine and a biosimilar across countries as well as indication extrapolation especially with respect to the risk of immunogenicity-related safety issues and diminished efficacy [17, 35]. However, an appreciable number of studies have now shown that such risks are unchanged when switching between an originator and a biosimilar [11, 21, 3644]. As a result, patient and physician organizations in Canada are now supporting non-medical switching [1], similar to initiatives among European countries such as France [45]. The growing body of evidence for biosimilars is also leading to suggestions to modify the current lengthy approval process and costs to enhance earlier access and strengthen competition [46]. There are though still concerns with switching among physicians that need to be addressed with education as these can negatively impact on their future utilization [4749]. Additional monitoring of patient outcomes in routine clinical practice should help further reduce possible concerns as well as potentially reduce the need for comparative clinical efficacy evidence as more originators lose their patents. This should reduce the investment needed for developing new biosimilars, and combined with developments in manufacturing [50], should help reduce future prices.

A number of other initiatives have also recently been undertaken in Canada to enhance the utilization of biosimilars. This includes the pan-Canadian Oncology Biosimilars Initiative to enhance successful adoption of biosimilars in oncology. British Columbia launched its Biosimilars Initiative in May 2019 promoting switching, with the savings used to lower premiums and co-pays where pertinent [1]. Other provinces are likely to follow.

We have also seen initiatives among other countries to enhance the use of biosimilars. Moorkens et al. and Vogler et al. have summarized these for Europe as well as provided future guidance to further enhance their uptake [51, 52]. More recently, Simoens et al. gave guidance on additional measures that could be introduced in Europe to fully realize the potential of biosimilars [53]. We are also seeing prescribing targets for biosimilars among European countries including national frameworks [5457]. However, there are still limited initiatives in some countries including Japan where currently no position statement regarding biosimilars has been included in treatment guidelines for any of the cancer societies [58]. This may change though with increasing pressure on resources and with the Japanese government now reviewing supportive measures for biosimilars [58]. Smeeding et al. recently highlighted a number of issues that payers in the US should consider as part of any strategy to increase the use of biosimilars [59].

Ongoing initiatives across countries, including both supply- and demand-side measures, have increased potential savings from biosimilars. Siu et al. suggest that by the third year of entry, potential savings from biosimilars in Canada could range from 13%–43% for acute use products such as granulocyte colony-stimulating factors (G-CSF) and erythropoietin (EPO) and 8%–43% for chronic-use products, e.g. anti-TNFs [1]. This is helped by price reductions for biosimilars in Canada ranging between 17% and 50% from the originator.

A number of European countries have introduced price-link policies for biosimilars to lower their prices and enhance savings, with other countries instigating measures, such as tendering to lower prices [52, 60, 61]. For instance, tendering among hospitals in Norway resulted in a 72% discount compared to its list price [60], and tendering in the UK will result in GBP 300 million (approximately US$386 million) savings from currently GBP 400 million-per-year (approximately US$514 million) spent on adalimumab [62]. In Germany, the current high use of adalimumab and anticipated savings resulted in biosimilars accounting for 28% of total prescriptions of adalimumab within eight weeks of launch [12]. In the US, it is estimated that biosimilars will reduce direct spending on biological drugs by US$54 billion from 2017 to 2026 [10, 63]; with savings likely to be higher with greater discounts than 20% to 30% currently seen [10]. Substantial discounts for biosimilars across Europe, greater than initial considerations [61], coupled with demand-side measures, have already resulted in their appreciably increased use in recent years. In some cases and countries in Europe, in view of their lower prices, biosimilars now account for the total market for EPO and G-CSF. This is especially the case among a number of Central and Eastern European countries [19].

However, there are concerns that originators are starting to substantially lower their prices potentially affecting future biosimilar availability and the sustainability of the marketplace as seen recently with adalimumab [9, 19, 64]. In addition, we are seeing originator companies defending manufacturing and other patents, as well as seeking to instigate hurdles in the US making it more difficult for insurers to place biosimilars on formularies in order to disrupt the biosimilar market [10, 65, 66]. Originator companies are also developing new formulations of their biologicals to try and further disrupt the biosimilar market building on previous evergreening tactics [19, 67]. There are also suggestions to lower the prices of originators in countries such as Belgium and the US over time, negating the need for biosimilars to further interfere with this market [68]. We will continue to monitor these developments and their implications.

In conclusion, Siu et al. have provided a comprehensive review of current and planned policies in Canada to enhance the use of biosimilars at competitive prices to benefit payers and patients. This is important for disease areas such as cancer with ever increasing prices for new medicines, which potentially threaten the sustainability of healthcare systems [69, 70]. It is also increasingly likely that health authorities will start reassessing prices and potential discounts for on-patent medicines for oncology and immunological diseases as more standard medicines used for pricing negotiations lose their patents [6, 71]. Siu et al. also remind key stakeholders to continually monitor developments with biosimilars including both supply- and demand-side initiatives as well as encourage countries to learn from each other to enhance their uptake. This is critical for health authorities with the instigation of disruptive tactics such as in The Netherlands with AbbVie and in the US with hurdles such as rebates and other strategies with insurers to limit biosimilar use. In addition, payers need to monitor the development of new formulations by originator manufacturers and plan for the implications.

Funding

There was no funding for this Commentary.

Competing interests: The authors have no conflicts of interest to declare.

Provenance and peer review: Commissioned; internally peer reviewed.

Authors

1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
2Division of Public Health Pharmacy and Management, School of Pharmacy, Faculty of Health Sciences, Sefako Makgatho Health Sciences University, Pretoria, South Africa
3Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden
4Istituto di Ricerche Farmacologiche ‘Mario Negri’ IRCCS, Milan, Italy
5KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Leuven, Belgium

References
1. Siu ECK, Tomalin A, West K, Anderson S, Wyatt G. An ever-evolving landscape: an update on the rapidly changing regulation and reimbursement of biosimilars in Canada. Generics and Biosimilars Journal (GaBI Journal). 2019;8(3):107-18. doi:10.5639/gabij.2019.0803.014
2. Ferro A, Boyce M. Biological therapies: a long way on from Jenner. Br J Clin Pharmacol. 2013;76(2):161-3.
3. Barker J, Girolomoni G, Egeberg A, Goncalves J, Pieper B, Kang T. Anti-TNF biosimilars in psoriasis: from scientific evidence to real-world experience. J Dermatolog Treat. 2019:1-7.
4. Kuenzig ME, Benchimol EI, Lee L, Targownik LE, Singh H, Kaplan GG, et al. The impact of inflammatory bowel disease in Canada 2018: direct costs and health services utilization. J Can Assoc Gastroenterol. 2019;2(Suppl 1):S17-S33.
5. IMS Institute for Healthcare Informatics. IMSH Institute global oncology trend report 2015 and 2020 report. June 2016 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.scribd.com/document/323179495/IMSH-Institute-Global-Oncology-Trend-2015-2020-Report.
6. Godman B, Bucsics A, Vella Bonanno P, Oortwijn W, Rothe CC, Ferrario A, et al. Barriers for access to new medicines: searching for the balance between rising costs and limited budgets. Front Public Health. 2018;6:328.
7. Transparency Market Research. Global TNF Inhibitors Market – Snapshot. 2018 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.transparencymarketresearch.com/tnf-inhibitors-market.html.
8. PRNewswire. Global tumor necrosis factor inhibitors drug market, dosage, price & clinical pipeline outlook 2024. 2018.
9. Hoen E’t. Humiragate: AbbVie’s desperate attempts to keep its monopoly. Medicines Law & Policy. 2019.
10. Stiff KM, Cline A, Feldman SR. Tracking the price of existing biologics when drugs enter the market. Expert Rev Pharmacoecon Outcomes Res. 2019;19(4):375-7.
11. Chan A, Kitchen J, Scott A, Pollock D, Marshall R, Herdman L. Implementing and delivering a successful biosimilar switch programme – the Berkshire West experience. Future Healthc J. 2019;6(2):143-5.
12. Grubert N. Biosimilar adalimumab achieves record launch impact in Germany—but government still plans reforms to boost biosimilar usage. Available from: https://www.linkedin.com/pulse/biosimilar-adalimumab-achieves-record-launch-impact-still-grubert/.
13. Baumgart DC, Misery L, Naeyaert S, Taylor PC. Biological therapies in immune-mediated inflammatory diseases: can biosimilars reduce access inequities? Front Pharmacol. 2019;10:279.
14. Putrik P, Ramiro S, Kvien TK, Sokka T, Pavlova M, Uhlig T, et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis. 2014;73(1):198-206.
15. Kostić M, Djakovic L, Šujić R, Godman B, Jankovic SM. Inflammatory bowel diseases (Crohn’s disease and ulcerative colitis): cost of treatment in Serbia and the implications. Appl Health Econ Health Policy. 2017;15(1):85-93.
16. Gotham D, Barber MJ, Hill A. Production costs and potential prices for biosimilars of human insulin and insulin analogues. BMJ Global Health. 2018;3(5):e000850.
17. O’Callaghan J, Barry SP, Bermingham M, Morris JM, Griffin BT. Regulation of biosimilar medicines and current perspectives on interchangeability and policy. Eur J Clin Pharmacol. 2019;75(1):1-11.
18. Migliavacca Zucchetti B, Nicolò E, Curigliano G. Biosimilars for breast cancer. Expert Opin Biol Ther. 2019:1-7.
19. European Commission. IQVIA Report 2018: The impact of biosimilar competition in Europe [home-page on the Internet]. [cited 2019 Sep 12]. Avail-able from: https://ec.europa.eu/docsroom/docu-ments/31642
20. Derbyshire M. Regulation of copy biologicals in China. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(2):75-6. doi:10.5639/gabij.2018.0702.015
21. Shina S. Pharma News. Top developments in biosimilars during 2018. Generics and Biosimilars Initiative Journal (GaBI Journal). 2019;8(1):32-9. doi:10.5639/gabij.2019.0801.004
22. Derbyshire M, Shina S. Patent expiry dates for biologicals: 2017 update. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(1):29-34. doi:10.5639/gabij.2018.0701.007
23. US Food and Drug Administration. Biosimilar product regulatory review and approval [home-page on the Internet]. [cited 2019 Sep 12]. Available from: https://www.fda.gov/files/drugs/published/Biosimilar-Product-Regulatory-Review-and-Approval.pdf
24. US Food and Drug Administration. Biosimilar product information. 2019 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.fda.gov/drugs/biosimilars/biosimilar-product-information
25. Pettit C. Biosimilars market is ripe for cost savings. The Center for Biosimilars. 2019 Jun 27.
26. European Medicines Agency. Guideline on similar biological medicinal products. 23 October 2014 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-similar-biological-medicinal-products-rev1_en.pdf
27. Niazi SK. Rationalizing FDA guidance on biosimilars — expediting approvals and acceptance. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(2):84-91. doi:10.5639/gabij.2018.0702.018
28. Jiménez-Pichardo L, Gázquez-Pérez R, Sierra-Sánchez JF. Degree of prescriber’s knowledge about variability in biological drugs ‘‘innovators’’ in manufacturing process. Eur J Clin Pharmacol. 2018;74(4):505-11.
29. Vezér B, Buzás Z, Sebeszta M, Zrubka Z. Authorized manufacturing changes for therapeutic monoclonal antibodies (mAbs) in European Public Assessment Report (EPAR) documents. Curr Med Res Opin. 2016;32(5):829-34.
30. CADTH Evidence Driven. CADTH Common Drug Review (CDR). 2019 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.cadth.ca/about-cadth/what-we-do/products-services/cdr
31. An Roinn Sáinte Department of Health. Ireland to open negotiations with Belgium, the Netherlands, Luxembourg and Austria on drug pricing and supply – Minister Harris. 2018.
32. European Observatory. How can voluntary cross-border collaboration in public procurement improve access to health technologies in Europe? [homepage on the Internet]. [cited 2019 Sep 12]. Available from: http://www.euro.who.int/__data/assets/pdf_file/0009/331992/PB21.pdf?ua=1
33. Henrard S, Arickx F. Negotiating prices of drugs for rare diseases. Bull World Health Organ. 2016;94(10):779-81.
34. O’Mahony JF. Beneluxa: what are the prospects for collective bargaining on pharmaceutical prices given diverse health technology assessment processes? Pharmacoeconomics. 2019;37(5):627-30.
35. Aladul MI, Fitzpatrick RW, Chapman SR. Healthcare professionals’ perceptions and perspectives on biosimilar medicines and the barriers and facilitators to their prescribing in UK: a qualitative study. BMJ Open. 2018;8(11):e023603.
36. Cohen HP, Blauvelt A, Rifkin RM, Danese S, Gokhale SB, Woollett G. Switching reference medicines to biosimilars: a systematic literature review of clinical outcomes. Drugs. 2018;78(4):463-78.
37. Gisondi P, Bianchi L, Calzavara-Pinton P, Conti A, Chiricozzi A, Fimiani M, et al. Etanercept biosimilar SB4 in the treatment of chronic plaque psoriasis: data from the Psobiosimilars registry. Br J Dermat. 2019;180(2):409-10.
38. Jørgensen KK, Olsen IC, Goll GL, Lorentzen M, Bolstad N, Haavardsholm EA, et al. Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trial. Lancet. 2017;389(10086):2304-16.
39. Stebbing J, Baranau YV, Baryash V, Manikhas A, Moiseyenko V, Dzagnidze G, et al. Double-blind, randomized phase III study to compare the efficacy and safety of CT-P6, trastuzumab biosimilar candidate versus trastuzumab as neoadjuvant treatment in HER2 positive early breast cancer (EBC). J Clin Oncol. 2017;35(15_suppl):510-.
40. Esteva FJ, Stebbing J, Wood-Horrall RN, Winkle PJ, Lee SY, Lee SJ. A randomised trial comparing the pharmacokinetics and safety of the biosimilar CT-P6 with reference trastuzumab. Cancer Chemother Pharmacol. 2018;81(3):505-14.
41. Komaki Y, Yamada A, Komaki F, Micic D, Ido A, Sakuraba A. Systematic review with meta-analysis: the efficacy and safety of CT-P13, a biosimilar of anti-tumour necrosis factor-alpha agent (infliximab), in inflammatory bowel diseases. Aliment Pharmacol Ther. 2017;45(8):1043-57.
42. Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, et al. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019;120(2):172-82.
43. Waller CF, Ranganna GM, Pennella EJ, Blakeley C, Bronchud MH, Mattano LA, Jr., et al. Randomized phase 3 efficacy and safety trial of proposed pegfilgrastim biosimilar MYL-1401H in the prophylactic treatment of chemotherapy-induced neutropenia. Ann Hematol. 2019;98(5):1217-24.
44. Tweehuysen L, Huiskes VJB, van den Bemt BJF, Vriezekolk JE, Teerenstra S, van den Hoogen FHJ, et al. Open-label, non-mandatory transitioning from originator etanercept to biosimilar sb4: six-month results from a controlled cohort study. Arthritis Rheumatol. 2018;70(9):1408-18.
45. GaBI Online – Generics and Biosimilars Initiative. Policies & Legislation – France aims to reach 80% biosimilar penetration by 2022 [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2019 Sep 12]. Available from: http://gabionline.net/Policies-Legislation/France-aims-to-reach-80-biosimilar-penetration-by-2022
46. Frapaise FX. The end of phase 3 clinical trials in biosimilars development? BioDrugs. 2018;32(4):319-24.
47. Teeple A, Ellis LA, Huff L, Reynolds C, Ginsburg S, Howard L, et al. Physician attitudes about non-medical switching to biosimilars: results from an online physician survey in the United States. Curr Med Res Opin. 2019;35(4):611-7.
48. Pineles D, Malter L, Liang PS, Arsuaga A, Bosworth B, Hudesman DP, et al. The nocebo effect and patient perceptions of biosimilars in inflammatory bowel disease. Eur J Clin Pharmacol. 2018;74(10):1361-2.
49. Smolen JS, Goncalves J, Quinn M, Benedetti F, Lee JY. Era of biosimilars in rheumatology: reshaping the healthcare environment. RMD Open. 2019;5(1):e000900.
50. DiMasi JA, Smith Z, Getz KA. Assessing the financial benefits of faster development times: the case of single-source versus multi-vendor outsourced biopharmaceutical manufacturing. Clin Ther. 2018;40(6):963-72.
51. Moorkens E, Vulto AG, Huys I, Dylst P, Godman B, Keuerleber S, et al. Policies for biosimilar uptake in Europe: an overview. PloS One. 2017;12(12):e0190147.
52. Vogler S, Schneider P. Do pricing and usage-enhancing policies differ between biosimilars and generics? Findings from an international survey. Generics and Biosimilars Initiative Journal (GaBI Journal). 2017;6(2):79-88. doi:10.5639/gabij.2017.0602.015
53. Simoens S, Le Pen C, Boone N, Breedveld N, Celano A, Llombart-Cussac A, et al. How to realize the potential of off-patent biologicals and biosimilars in Europe? Guidance to policymakers. Generics and Biosimilars Initiative Journal (GaBI Journal). 2018;7(2):70-4. doi:10.5639/gabij.2018.0702.014
54. Health Improvement Scotland. Biosimilar medicines: a national prescribing framework. 2018 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: http://www.healthcareimprovementscotland.org/our_work/technologies_and_medicines/programme_resources/biosimilar_medicines_framework.aspx
55. All Wales Medicine Strategy Group. National Prescribing Indicators 2018–2019. 2018 [home-page on the Internet]. [cited 2019 Sep 12]. Available from: http://www.awmsg.org/docs/awmsg/medman/National%20Prescribing%20Indicators%202018-2019.pdf
56. NHS Scotland. Secondary Care National Therapeutic Indicators 2018/19 [homepage on the Internet]. [cited 2019 Sep 12]. Available from: https://www.therapeutics.scot.nhs.uk/wp-content/uploads/2018/08/Secondary-Care-National-Therapeutic-Indicators-Version-1.0.pdf
57. Underwood G. The biosimilars era. Pharma Times. 2018.
58. Hara F, Tajima K, Tanabe K. Current situation and challenges regarding biosimilars in Japan: an example of trastuzumab biosimilars for breast cancer. Future Oncol. 2019;15(12):1353-61.
59. Smeeding J, Malone DC, Ramchandani M, Stolshek B, Green L, Schneider P. Biosimilars: considerations for payers. PT. 2019;44(2):54-63.
60. Matusewicz W, Godman B, Pedersen HB, Fürst J, Gulbinović J, Mack A, et al. Improving the managed introduction of new medicines: sharing experiences to aid authorities across Europe. Expert Rev Pharmacoecon Outcomes Res. 2015;15(5):755-8.
61. Godman B. Health authority perspective on biosimilars. Generics and Biosimilars Initiative Journal (GaBI Journal). 2013;2(1):10-11. doi:10.5639/gabij.2013.0201.010
62. Davio K. After Biosimilar deals, UK spending on adalimumab will drop by 75%. 2018. The Center for Biosimilars.
63. Mulcahy AW, Hlavka JP, Case SR. Biosimilar cost savings in the United States: initial experience and future potential. Rand Health Q. 2018;7(4):3.
64. Sagonowsky E. AbbVie’s massive Humira discounts are stifling Netherlands biosimilars: report. 2019 Apr 2. FiercePharma.
65. Reinke T. Show us (the U.S.) the savings. Manag Care. 2019;28(1):9-10.
66. Kellaher C. AbbVie, Boehringer settle U.S. patent dispute over drug Humira. The Wall Street Journal. 2019 May 14.
67. Vernaz N, Haller G, Girardin F, Huttner B, Combescure C, Dayer P, et al. Patented drug extension strategies on healthcare spending: a cost-evaluation analysis. PLoS Med. 2013;10(6):e1001460.
68. Atteberry P, Bach PB, Ohn JA, Trusheim M. Biologics are natural monopolies (Part 1): why biosimilars do not create effective competition. Health Affairs Blog. 2019 [cited 2019 Sep 12]. Available from: https://www.healthaffairs.org/do/10.1377/hblog20190405.396631/full
69. Godman B, Wild C, Haycox A. Patent expiry and costs for anti-cancer medicines for clinical use. Generics and Biosimilars Initiative Journal. 2017;6(3):105-6. doi:10.5639/gabij.2017.0603.021
70. Ghinea H, Kerridge I, Lipworth W. If we don’t talk about value, cancer drugs will become terminal for health systems. The Conversation. 2015 Jul 28.
71. Godman B, Hill A, Simoens S, Kurdi A, Gulbinovič J, Martin AP. Pricing of oral generic cancer medicines in 25 European; findings and implications. Generics and Biosimilars Initiative Journal. 2019;8(2):49-70. doi:10.5639/gabij.2019.0802.007

Author for correspondence: Brian Godman, BSc, PhD, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK

Disclosure of Conflict of Interest Statement is available upon request.

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