The European Union, considered the most seasoned user of biosimilars, has approved the highest number of biosimilars worldwide.
It is no secret that progress in biosimilar product approval has been slow within the US healthcare market. The first biosimilar approved in the United States in 2015 was already available in 60 other countries around the world.1 In fact, more than 700 million patient days have been documented from a decade of biosimilar experience within the European Union.2 The European Union, considered the most seasoned user of biosimilars, has approved the highest number of biosimilars worldwide (with more than 30 products currently approved).3
As of October 1, 2017, there are only 7 FDA-approved biosimilars in the United States, and only 3 have made it to market. While 60% of overall global biologic sales occur in the US, 9 out of 10 biosimilar product sales in 2016 were in the European Union.2 With such significant differences in biosimilar markets across oceans, a large window of opportunity becomes available to gain key learnings from international counterparts.
It is important to recognize that the uptake and acceptance of biosimilars within the European Union varies greatly not only by country, but by therapeutic area as well. The amount of government involvement, reimbursement systems, and tender procurement policies all contribute to variations in adoption rates among regions. Of course, the regulatory and payer environment also varies greatly among EU member states and the United States. Despite these differences, it is important to not dismiss the decade-long EU biosimilars experience, including overcoming barriers to enhance product uptake. Trends and lessons can be applied to the domestic market to understand the potential impact of biosimilars on patient care and accessibility.
As providers and patients continue to gain familiarity with biosimilars in the United States, the European Union has been able to make significant progress in raising stakeholder awareness, despite initial concerns with the category of drugs as well. In fact, education remains a priority in the European Union, with regulatory bodies such as the European Commission (EC) and European Medicines Agency (EMA) leading stakeholder education on biosimilar medicines.2 In Denmark, where a national tender system is used, the infliximab biosimilar has become a first-line product for biological treatment in both rheumatology and gastroenterology, resulting in immediate uptake of the biosimilar in clinical practice.2 As part of the conversion, the government consulted with payers, regulators, and physicians to develop patient education resources.2 There are key lessons to learn from the European Union on the significant need for multi-stakeholder, multifaceted biosimilar education within the United States.
Ensuring continuous engagement of providers, payers, and patients has proven to be critical to EU biosimilar acceptance. Additionally, involvement of regulatory agencies in the education process not only signifies the importance of these products, but also serves as a “non-branded” source of education to support overall biosimilar awareness. While the FDA continues to develop guidance on biosimilars, intentional educational efforts with various stakeholders, including providers, payers, and patients will remain crucial. Ultimately, empowerment through education will help healthcare members and patients make informed decisions regarding treatment options.
Clinical and safety learnings with EU-approved biosimilars should also be considered in the United States. Both the EMA and FDA biosimilar approval pathways rely heavily on analytical and physicochemical comparative reviews of molecules.3,4 The non-clinical and clinical data needed to approve biosimilars are less extensive than requirements for originator biologic approval.3,4 By demonstrating biosimilarity, the biosimilar is able to rely on the safety and efficacy experience gained with the reference product.3,4 With that said, extrapolation of indications occurs via both regulatory pathways.3,4 The EMA, unlike the FDA, does not regulate interchangeability, switching, or substitution; rather these fall within the authority of each EU member state.3 There are different position statements on physician-led switching within the European Union, but overall, it is common practice.2,5 The United States can utilize EU clinical experiences to help gain insights on safety/immunogenicity outcomes with biosimilars in both extrapolated indications as well as biologic-biosimilar “switching,” including outcomes from the NOR-SWITCH trial.6 This year, the EC and EMA jointly prepared an information guide for healthcare providers on biosimilars in the European Union.3 The guide states, “Over the last 10 years, the EU monitoring system for safety concerns has not identified any relevant difference in the nature, severity or frequency of adverse effects between biosimilars and their reference medicines.”3 Another publication concluded that EU-licensed biosimilars are interchangeable, and a switch between products is “not expected to trigger or enhance immunogenicity.”7
Biologics are the most expensive drug category—a common trait among the Humira, Remicade, Avastin, and Herceptin biologics marketed in the European Union and the United States, which continue to be “repeat offenders” on the top drug expenditure lists across countries.3,8 Emergence of biosimilars increases treatment options for patients, creates further competition in the marketplace, and contributes to significant cost reduction, as confirmed in a recent report prepared by QuintilesIMS on biosimilar competition in Europe.9 According to the 2008 National Institute for Health and Care Excellence (NICE) guidelines, epoetin was considered clinically effective for anemia due to cancer treatment, but it was not considered cost effective.2 However, 6 years later (after the entrance of biosimilars), the NICE guidelines were updated to state that epoetin was both clinically effective and cost effective.2 Biosimilars have the potential to allow patients access to therapeutic options that may not have been previously accessible. The EU has also gathered evidence to highlight the first-to-market advantage for capturing market share.9 For example, the average biosimilar market share in 2016 across the European Union, for both anti—tumor necrosis factor inhibitors and erythropoietin were greater than 70% for the first biosimilar launched.9 With that said, the potential impact of a delayed US market release, subsequent to an FDA complete response letter for example, can significantly impact market success.
From education, clinical experiences, and market observations, the European Union offers a wealth of information on biosimilars that can be utilized in the United States. Despite geographical differences, including regulatory and reimbursement structures, the potential impact of biosimilars on healthcare costs and patient access are significant. The United States has the opportunity to apply lessons learned from the EU to help close the knowledge gap on biosimilars and expedite the development of strategies to overcome barriers. Only through collaborations between various stakeholders can the United States develop a successful and robust biosimilars market.
1. Rosenthal M. FDA approves Zarxio, first U.S. biosimilar. Pharmacy Practice News website. pharmacypracticenews.com/New-Drug-Approvals/Article/03-15/FDA-Approves-Zarxio-First-U-S-Biosimilar/29675/ses=ogst. Published March 6, 2015. Accessed March 18, 2017.
2. A van den Hoven. Biosimilar medicines: practical EU experience and perspectives. Sept 12, 2017. 2017 AAM Biosimilars Council Conference. http://biosimilarscouncil.org/wp-content/uploads/2017/09/BIO17-Agenda.pdf.
3. Biosimilars in the EU: Information guide for healthcare professionals. European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/Leaflet/2017/05/WC500226648.pdf. Updated April 27, 2017. Accessed September 1, 2017.
4. Christl L. Overview of the regulatory pathway and FDA’s guidance for the development and approval of biosimilar products in the US. FDA website. fda.gov/downloads/advisorycommittees/committeesmeetingmaterials/drugs/arthritisadvisorycommittee/ucm513087.pdf.
5. Positioning statements on physician-led switching for biosimilar medicines. Medicines for Europe website. medicinesforeurope.com/wp-content/uploads/2017/03/M-Biosimilars-Overview-of-positions-on-physician-led-switching.pdf. Published June 2017. Accessed September 20, 2017.
6. Jørgensen KK, Olsen IC, Goll GL, 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):2304-231 doi: 10.1016/S0140-6736(17)30068-5.
7. Kurki P, van Aerts L, Wolff-Holz E, Giezen T, Skibeli V, Weise M. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31(2):83-91. doi: 10.1007/s40259-017-0210-0.
8. Schumock GT, Li EC, Wiest MD, et al. National trends in prescription drug expenditures and projections for 2017. Am J Health Syst Pharm. 2017;74(15):1158-1173. doi: 10.2146/ajhp170164.
9.The impact of biosimilar competition in Europe. Quintiles IMS website. medicinesforeurope.com/wp-content/uploads/2017/05/IMS-Biosimilar-2017_Vpdf. Published May 2017. Accessed September 20, 2017.