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Many European healthcare systems have struggled to fund biologic therapies for the numerous patients who need them, and cost containment in this area has been recognized as a priority by the European Commission (EC). The European Medicines Agency (EMA) has led the world in the development of regulatory guidelines for the development and assessment of biosimilars, establishing key principles of comparability that have been adopted by many other regions around the world. By January 2016, 22 biosimilars based on eight originator products – including the world’s first monoclonal antibody biosimilar – had been approved for use in Europe (see section below: Approved biosimilars in Europe). In 2013, biosimilars were responsible for around a quarter of all sales of biologics for which EU patents had expired. The European experience with biosimilars has revealed substantial cost savings for healthcare providers and patients, with no reports of untoward effects or unexpected adverse events with biosimilars in Europe to date. 


Current access to originator biologics in Europe   +

The European biologic market is growing at an annual rate of approximately 5.5%. By comparison, the total pharmaceutical market growth in Europe between 2012 and 2013 was 1.9%. By late 2014, biologic medicines accounted for 27% of pharmaceutical sales in Europe.1

Although biologics have transformed clinical outcomes for patients throughout Europe, their high cost has put a heavy strain on European healthcare systems. The European Commission has stated that the cost of biologics compared with small-molecule medicines is a challenge for most payers.2 For example:

  • In more than 50% of European countries the annual cost of a biologic disease-modifying anti-rheumatic drug (DMARD) for rheumatoid arthritis can exceed the per capita GDP by as much as 11 times.3
  • In France, the cost of cancer therapies has been doubling every 4 years.4
  • Public hospitals in Portugal are experiencing difficulties in the approval of prescriptions of biologics for patients with rheumatoid arthritis because of the high cost of biologics and the tough budget constraints they face.5
  • The cost of insulins contributes markedly to overall healthcare expenditure for patients with diabetes who make up approximately 8.5% of the adult European population (2010 estimate).6 The prevalence of diabetes ranges from 2.1% in Iceland to 12.0% in Germany, and is predicted to grow significantly in coming years.7

"Price – just as much as safety and efficacy – has proved a hot topic for nearly 20,000 oncology experts at the  European Society for Medical Oncology (ESMO) 2014 congress in Madrid." 12

The cost of biologics has put them beyond the reach of many patients in Europe, in particular those who have to contribute a major portion of their treatment costs because of lack of state funding or inadequate private insurance coverage. Patients with chronic conditions are most vulnerable.

  • An employee in Europe receiving the national minimum wage has to work 1038 days (on average) to pay for a month of treatment with a biologic DMARD, compared with only 19 days to fund a non-biologic DMARD. Overall, approximately 40% of the total European population has severely restricted access to these therapies.3
  • In Central and Eastern Europe, reimbursement disparities mean that less than 5% of all patients with rheumatoid arthritis are treated with biologics, compared with Western Europe where the average usage is 11–12%.8,9 Similar discrepancies between Eastern and Western Europe in terms of access to expensive cancer biologics were recently reported by the European Society of Medical Oncology (ESMO).10
  • In the UK, at least eight breast cancer biologics with proven overall survival benefit have been rejected between 2011 and 2014 by the National Institute for Health and Care Excellence (NICE) for reimbursement on the National Health Service (NHS)11 because of cost.
Regulatory guidelines in Europe   +

The European Medicines Agency (EMA) has led the way in the development of regulatory guidelines for the development and assessment of biosimilars. Their initial overarching biosimilar guidelines were originally issued in 2005 and updated in 2014.13
  • Most non-EU countries have adopted a large proportion of the EU biosimilar guidelines, for example Australia, New Zealand, Canada, Japan, Korea, Singapore, South Africa and Switzerland. In addition, the World Health Organization (WHO) has used the principles contained in the 2005 EMA guidance as the basis for its own guidelines for Similar Biotherapeutic Products (SBPs).13
  • In addition to the overarching biosimilar guidelines, the EMA has also pioneered a range of product-specific guidelines to aid the development of specific classes of biosimilar products, including recombinant follicle-stimulating hormone (FSH), interferon beta, erythropoietins, low-molecular-weight heparins, interferon alpha, filgrastim (G-CSF), somatropin, human insulin and insulin analogues, and monoclonal antibodies.13
  • To gain marketing authorization in the EU, biosimilars need to demonstrate similar quality, safety, and efficacy to their reference medicinal product already approved in the EU. Biosimilar product approval does not include any recommendation regarding interchangeability or substitution with their originator product, as these remain the decision of national regulatory authorities across Europe.13
Approved biosimilars in Europe   +

By August 2016, 23 biosimilars based on eight originator products had been approved by the EMA, more than anywhere else in the world. The approved products include the world’s first monoclonal antibody biosimilar.

Biosimilars approved for use in Europe since 200614

Product INN
Number of biosimilar versions licensed in Europe
Year(s) of approval
Somatropin
  2* 2006

Epoetin alfa

3 2007

Epoetin zeta

2 2007

Etanercept

 1  2016 

Filgrastim

  9* 2008–2014

Infliximab

3 2013–2016

Follitropin alfa

2 2013–2014
Insulin glargine  1  2014

*One somatropin biosimilar and one filgrastim biosimilar were later withdrawn for commercial reasons

European experience with biosimilars since they were first introduced in 2006 has revealed no reports of untoward effects or unexpected adverse events compared with the originator biologics.2
Market uptake and financial impact of biosimilars in Europe   +

Biosimilars are now in clinical use across almost all EU member states. Uptake was fairly slow initially due to their unfamiliarity but has since begun to accelerate.

  • In mid-2016, it was revealed that, between 2006 and 2014, biosimilar medicines increased patient access by 44% overall in the European Union 5 countries (EU5: France, Germany, Italy, Spain, and the UK).15 
  • By 2013, biosimilars made up approximately a quarter of all sales of biologics for which EU patents had expired.16,17
  • As of September 2015, the biosimilars market in the EU5 stood at US $490 million, a massive increase since 2007 when the market was just being established. Filgrastim biosimilars are leading the way when it comes to market penetration, reaching market shares of 60–80% across the EU.18
  • Germany is leading the uptake of biosimilars, followed by the UK and France. Italy and Spain showed initial cultural resistance but are now catching up (Figure 1).1 

Figure 1: Biosimilar sales across the EU5

 
Source: IMS Health, MIDAS, MAT Dec 2013

Current differences in the use of biosimilars and competition dynamics across European markets mainly reflect local adoption of treatment practices and guidelines influenced by funding decisions and payer actions.1

  • With regard to cost savings, mean price discounts of 15–40% (compared with originators) have been seen with biosimilar products introduced into the European market, including somatropin, epoetin, and filgrastim.19,20
  • However, a discount of 45% for an infliximab biosimilar was negotiated in France by a major hospital group,21 while in Norway and Denmark, biosimilars of infliximab are available at a 70% discount.22,23 Physicians in Danish and Norwegian hospitals can now treat a patient for 3 years with biosimilar infliximab for the same price as 1 year with the originator.22,23  
  • In Germany, the use of biosimilar erythropoietin, between 2007 and 2011, led to over €600 million in savings.24
  • Market competition is already at work; in Germany, price reductions of 30–40% have been seen for originator epoetin and filgrastim since the introduction of biosimilar competitors at significantly lower market prices.25–27 In the UK, the price of originator infliximab was lowered by approximately 25% in 2015, in the face of competitive pressure from two biosimilars.28
The future of biosimilars in Europe   +

  • According to recent estimates, the introduction of biosimilars could save eight European countries (Germany, France, Italy, UK, Spain, Sweden, Poland and Romania) up to €33.4 billion by 2020. The largest savings are anticipated for France, Germany and the UK.29
  • Biosimilar monoclonal antibodies are expected to produce the greatest savings – up to €20.4 billion by 2020. Projections for biosimilar erythropoietins over the same time period range from €9.4–11.2 billion, and for granulocyte colony-stimulating factors from €0.7–1.8 billion.29
  • A 2014 forecast estimated that the introduction of biosimilar infliximab within six central and eastern European countries could allow 1,205 additional patients with rheumatoid arthritis (RA) to receive biologic therapy and up to 1,790 if interchangeability is permitted.30
  • A similar forecast in 2015 looking at the use of biosimilar infliximab for inflammatory autoimmune conditions in EU countries suggested that 2,602 additional patients could be treated per year in Germany (based on a 30% discount).31
  • Rheumatologists in five EU countries have predicted at least 30% of new RA patients eligible for biologics will receive biosimilars. Measures to mandate use of RA biosimilars for new patients in the EU appear likely, but switching from originators is expected to be optional for now.32
  • The UK’s National Institute for Health and Care Excellence (NICE) has recommended that infliximab biosimilars, Remsima and Inflectra, should be used ahead of the originator Remicade.33 NICE has also published a new resource to support the introduction of Inflectra and Remsima into clinical use.34

The European Commission expects several new classes of biosimilar medicines to be submitted for approval in Europe in the coming years.A number of ‘blockbuster’ biologics are expected to lose their EU patents before 2020, including leading treatments for breast cancer, diabetes, multiple sclerosis and rheumatoid arthritis.35,36 The opportunities for clinical investigators in biosimilar research are expected to escalate throughout Europe.

References   +

  1. IMS Health, October 2014. Assessing biosimilar uptake and competition in European markets. http://www.imshealth.com/files/web/IMSH%20Institute/Healthcare%20Briefs/Assessing_biosimilar_uptake_and_competition_in_European_markets.pdf. Accessed 2 November 2015.
  2. European Commission, 2013. Consensus Information Document. What you need to know about Biosimilar Medicinal Products. 
  3. Putrik P, Ramiro S, Kvien TK et al. Inequities in access to biologic and synthetic DMARDs across 46 European countries. Ann Rheum Dis (2014) 73:198–206.
  4. Cornes P. The economic pressures for biosimilar drug use in cancer medicine. Target Oncol (2012) 7 (Suppl 1):S57–67.
  5. Laires PA, Mesquita R, Veloso A et al. Patient’s access to healthcare and treatment in rheumatoid arthritis: The views of stakeholders in Portugal. BMC Musculoskel Disord (2013) 14:279.
  6. Rotenstein LS, Ran N, Shivers JP et al. Opportunities and challenges for biosimilars: What’s on the horizon in the global insulin market? Clin Diabetes (2012) 30:138–150.
  7. IDF Diabetes Atlas, Sixth Edition (Europe).
  8. Kobelt G & Kasteng F. Access to innovative treatments in rheumatoid arthritis in Europe. A report prepared for the European Federation of Pharmaceutical Industry Associations (EFPIA). October 2009.
  9. Laires PA, Exposto F, Mesquita R et al. Patients’ access to biologics in rheumatoid arthritis: A comparison between Portugal and other European countries. Eur J Health Econ (2013) 14:875–885.
  10. ESMO 2014 press release, 28 September 2014. Treatments for advanced cancer less available in Eastern Europe, reveals ESMO survey. http://www.esmo.org/Conferences/ESMO-2014-Congress/Press-Media/Treatments-for-Advanced-Cancer-Less-Available-in-Eastern-Europe-Reveals-ESMO-Survey. Accessed 10 December 2015.
  11. FiercePharma, 23 April 2014. NICE rejects Roche's hot new breast cancer drug Kadcyla, then invites negotiations. http://www.fiercepharma.com/story/nice-rejects-roches-hot-new-breast-cancer-drug-kadcyla-then-invites-negotia/2014-04-23. Accessed 10 December 2015.
  12. Reuters, 30 September 2014. New cancer therapy comes of age, cost a 'toxic' side effect. http://www.reuters.com/article/2014/09/30/us-health-cancer-costs-iduskcn0hp19z20140930. Accessed 10 December 2015.
  13. EMA biosimilars. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000408.jsp. Accessed 10 December 2015.
  14. EMA European Public Assessment Reports. Biosimilars. http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Flanding%2Fepar_search.jsp&mid=WC0b01ac058001d124&searchTab=searchByAuthType&alreadyLoaded=true&isNew
    Query=true&status=Authorised&keyword=Enter+keywords&searchType=name&taxonomyPath=&treeNumber=&searchGenericType=biosimilars&generics
    KeywordSearch=Submit
    . Accessed 29 January 2016.
  15. Biosimilar News, 28 April 2016. 10 years of biosimilar medicines in Europe: transforming healthcare. http://www.biosimilarnews.com/10-years-of-biosimilar-medicines-in-europe-transforming-healthcare. Accessed 15 June 2016.
  16. EuropaBio Guide on Biosimilars in Europe, September 2014.
  17. IMS Health Thought Leadership, November 2013. The global use of medicines: Outlook through 2017. Report by the IMS Institute for Healthcare Informatics.
  18. GaBI Online, 8 August 2014. Use of biosimilars in Europe differs across countries. http://www.gabionline.net/Reports/Use-of-biosimilars-in-Europe-differs-across-countries. Accessed 2 November 2015.
  19. Rovira J, Espín J, García L & Olry de Labry A. The impact of biosimilars’ entry in the EU market. European Commission 2011.
  20. Datamonitor Healthcare, March 2015. The evolution of the biosimilars landscape. http://www.datamonitorhealthcare.com/biosimilars-landscape-evolution/. Accessed 2 November 2015. [Subscription required]
  21. GaBI Online, 31 July 2015. Biosimilar infliximab offered to French hospitals at 45% discount. http://www.gabionline.net/Biosimilars/News/Biosimilar-infliximab-offered-to-French-hospitals-at-45-discount. Accessed 2 November 2015.
  22. GaBI Online, 13 March 2015. Huge discount on biosimilar infliximab in Norway. http://www.gabionline.net/Biosimilars/General/Huge-discount-on-biosimilar-infliximab-in-Norway. Accessed 2 November 2015.
  23. Firstword Pharma, June 2015. ViewPoints: Denmark joins Norway in securing a 60 percent-plus discount for biosimilar Remicade – what impact on the rest of Europe? http://www.firstwordpharma.com/footer/benefits?tsid=17#axzz3pognrf8K. Accessed 2 November 2015. [Subscription required]
  24. Turner M, Walsh K, Whitehouse J. Economic evaluation of epoetin alfa Hexal/Binocrit compared to darbepoetin alfa (Aranesp) in the treatment of chemotherapy-induced anemia (CIA) in Germany. Poster presented at ISPOR 16th Annual European Conress, Dublin, Ireland, 2–6 November 2013.
  25. Mellstedt H. Anti-neoplastic biosimilars – the same rules as for cytotoxic generics cannot be applied. Ann Oncol (2013) 24(Suppl 5):v23–v28.
  26. Haussler B. Cost savings potential of biosimilars in the German health care system. In: Life Science in the Capital Market Biosimilars. DVFA, 2010.
  27. Pharmaceutical Journal, 17 November 2014. Forces driving the evolution of biologics into biosimilars and biobetters. http://www.pharmaceutical-journal.com/news-and-analysis/features/forces-driving-the-evolution-of-biologics-into-biosimilars-and-biobetters/20067091.article. Accessed 2 November 2015. [Subscription required]
  28. Fierce Pharma, 26 October 2015. Merck discounts Remicade in UK as it tries to fend off biosimilars. http://www.fiercepharma.com/story/merck-discounts-remicade-uk-it-tries-fend-biosimilars/2015-10-26. Accessed 29 January 2016.
  29. Haustein R, de Millas C, Höer A & Häussler B. Saving money in the European healthcare systems with biosimilars. GaBI Journal (2012) 1(3–4):120–126.
  30. Brodszky V, Baji P, Balogh O et al. 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.
  31. Jha A, Upton A, Dunlop WC et al. The budget impact of biosimilar infliximab (Remsima®) for the treatment of autoimmune diseases in five European countries. Adv Ther (2015) 32(8):742‒56.
  32. PR Newswire, 3 September 2015. Cost-constrained payers across the eu5 welcome the launch of biosimilars in the RA market and anticipate encouraging or imposing the prescription of these agents to control the spending of high-cost biologics. http://www.prnewswire.com/news-releases/cost-constrained-payers-across-the-eu5-welcome-the-launch-of-biosimilars-in-the-ra-market-and-anticipate-encouraging-or-imposing-the-prescription-of-these-agents-to-control-the-spending-of-high-cost-biologics-300137078.html. Accessed 2 November 2015.
  33. PM Live, 22 June 2015. NICE recommends infliximab biosimilars ahead of Remicade. http://www.pmlive.com/pharma_news/nice_recommends_infliximab_biosimilars_ahead_of_remicade_761827. Accessed 2 November 2015.
  34. The National Institute for Health and Care Excellence (NICE). Introducing biosimilar versions of infliximab: Inflectra and Remsima. NICE technology appraisal support [HTTA329]; July 2015. https://www.nice.org.uk/guidance/htta329. Accessed 2 November 2015.
  35. Biosimilars: A global perspective of new market opportunities, threats and critical strategies. Thomson Reuters BioWorld, 2014. http://www.bioworld.com/content/biosimilars-global-perspective-new-market-opportunities-threats-and-critical-strategies-2014. Accessed 10 December 2015.
  36. GaBI Online, 29 June 2012. US$67 billion worth of biosimilar patents expiring before 2020. http://www.gabionline.net/Biosimilars/General/US-67-billion-worth-of-biosimilar-patents-expiring-before-2020. Accessed 10 December 2015.
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