Navigating the road to successful biosimilar uptake in Europe – Still some way to go?
By Xcenda
The biologic drug segment, including biosimilar medicines, is one of the fastest growing with regard to pharmaceutical research and development and makes up a significant share of healthcare spending in Europe. The EU represents an attractive market for biosimilar manufacturers as the number 1 in biosimilar regulatory approvals in the last 10 years worldwide. As of 1 September 2022, 86 biosimilars have been approved by the European Medicines Agency (EMA) since 2006, mainly in the therapeutic areas of cancer, diabetes, and rheumatoid arthritis. When it comes to funding, it is evident that biosimilars are appealing to payers since they offer the same clinical benefit as the originator drug at a lower price, leading to savings which may be allocated elsewhere in the healthcare system. For example, it was estimated that savings from the use of biosimilars for erythropoietin, granulocyte colony-stimulating factors, and monoclonal antibodies amounted to €11.8 to €33.4 billion between 2007 and 2020 in Europe.
The EMA and the UK Medicines and Healthcare products Regulatory Agency (MHRA) have recently updated guidance on the interchangeability of biosimilar medicines with the aim to eliminate uncertainties among stakeholders on the use of biosimilars in clinical practice. They state that biosimilars approved in the EU and UK are interchangeable with their reference products or another biosimilar of the same reference product. This differs from regulations in other markets, such as the United States where the Food and Drug Administration (FDA) decides on interchangeability of biosimilars on a case-by-case basis and only if additional clinical data on alternating treatment between the reference and biosimilar medicine has been submitted.
EMA’s guidance on the interchangeability of biosimilars does not necessarily imply automatic substitution at the pharmacy level (i.e. dispensing of the cheapest product even if the originator or biosimilar brand name is written on the prescription), which is, and will remain, the remit of the individual EU member states (Table 1). Likewise, any other measures to steer the pricing, reimbursement, and use of biosimilars lie within national competences, which leads to differences in prices and biosimilar uptake across European countries.
Although the EU is a pioneer in authorizing biosimilar medicines, national policies are highly impacting their availability for patients in the individual markets and their potential and associated advantages are not yet fully exploited in the European countries.
Table 1. Overview of biosimilar availability and regulations in EU-4 and UK
AEMPS – Spanish Agency of Medicines and Medical Devices; EU-4 – France, Germany, Italy, Spain; HTA – health technology assessment; UK – United Kingdom.a State as of July 2022.
b Since April 2022, pharmacists are allowed to replace the prescribed biological drug for two molecules with their biosimilar: filgrastim and pegfilgrastim. This is only allowed if the physician has not excluded this possibility by placing an explicit and justified note on the prescription.
c State as of 17 October 2022.
d In 2021.
e The proposed price has to be at least equal to that established by decree by the Minister of Health in relation to the expected sales volumes.14
f State as of January 2023.
g The generics and biosimilars plan developed by the Ministry of Health is currently being assessed by the Autonomous Regions. In its current state, interchangeability and different incentives to increase biosimilar uptake are included.24
h The shortened dossier includes a proof of bioequivalency and a cost analysis.
Sources: 1. République française, 2022. 2. l’Assurance Maladie, 2022. 3. HAS, 2021. 4. Kim et al., 2021. 5. Vogler et al., 2021. 6. GaBI Online, 2022a. 7. The Connexion, 2022. 8. Pro Generika e. V. Arbeitsgemeinschaft Pro Biosimilars, 2022. 9. Arbeitsgemeinschaft Pro Biosimilars, no date. 10. Egualia, 2022. 11. AIFA, 2023. 12. AIFA, 2020. 13. AIFA, 2018. 14. Repubblica Italiana, 2013. 15. Guidotti et al., 2021. 16. BioSim, 2023. 17. Zozaya et al., 2017. 18. Universidad Complutense Madrid & Hygeia Consulting, 2020. 19. García-Goñi et al., 2021. 20. BioSim, 2022. 21. Dictionary of medicines and devices (dm+d) database. 22. MHRA, 2022. 23. NHS England, no date. 24. Ministerio de Sanidad, Consumo y Bienestar Social, 2019.
Table 1 shows that the number of biosimilars available is similar across EU-4 countries and the UK. However, actual market penetration varies significantly. Italy has the highest biosimilar uptake among these countries with a biosimilar market share of 43% vs 57% for originator drugs in 2021. In comparison, in Germany only 15% of biopharmaceuticals prescribed by the Statutory Health Insurance were biosimilars or bioidenticals in 2021. This may be due to small price differences between biologics and biosimilars as a result of no pricing rules for biosimilars in Germany, meaning few savings from biosimilar products. In France and Spain, biosimilar penetration reached 25% in 2021 and 28% in 2020, respectively. A survey among physicians and pharmacists in Spain found the main barriers to biosimilar uptake were the lack of confidence in biosimilar long-term efficacy and safety, and knowledge gaps concerning such issues as biosimilar development and interchangeability, resulting in a high reluctance to switch from an originator product.
In some countries, high variability in biosimilar uptake is seen even between regions for some molecules. For example, in 4 Italian regions, biosimilars accounted for 100% of bevacizumab use between January and August 2022, compared with just 43.8% in one Southern region. Similarly, in Spain the inpatient biosimilar use of rituximab and trastuzumab varied between 35.9% and 0% across regions in 2018.
The UK has been successful in increasing biosimilar uptake through the implementation of several demand and supply side measures over the last years, leading to estimated cumulative savings of $275 million in 2017. In August 2019, biosimilar uptake of adalimumab, etanercept, infliximab, rituximab, and trastuzumab ranged from 74% for adalimumab to 95% for infliximab in England. However, there is a high variability in biosimilar uptake between National Health Service (NHS) Trusts ranging from 0% to 100% uptake for some molecules.
While the Spanish Agency of Medicines and Medical Devices has yet to issue concrete guidance on interchangeability and switching of biosimilars with their originators, in the other countries it is the physicians’ decision whether to prescribe a biosimilar or the originator. Automatic switching at pharmacy level is usually not allowed. France is an exception, where a 2022 law authorizes pharmacists, under certain conditions, to automatically substitute biosimilars. Currently, it is only possible for two molecules, filgrastim and pegfilgrastim, but it is planned to progressively add new molecules.
Similarly, a new law for automatic substitution is currently being discussed in Germany to drive biosimilar uptake. The initiative was kicked off in June 2019, when the German Bundestag passed the Act for Greater Safety in the Supply of Medicines (GSAV). This included an amendment to Section 129 of the German Social Code, Book V (SGB V) providing for the automatic substitution of biotechnologically produced medicines in pharmacies. The first step in this process is for the Federal Joint Committee (G-BA) to establish interchangeability for the biosimilar and the biological reference drug. The committee published guidance for physicians to support economical prescribing in August 2020, detailing approved biosimilars. The framework to guide pharmacies regarding automatic substitution was planned for 2022 but received a lot of criticism from the pharmaceutical industry and medical community stating the decision-making authority should remain with physicians, resulting in the implementation being postponed. With the GKV-Financial Stabilization Act (GKV-FinG), the deadline is extended until 16 August 2023 and automatic substitution will initially only apply to biosimilars that are parenteral preparations of biological finished medicinal products for direct medical use in patients. Despite criticism from the pharmaceutical industry, automatic substitution is a measure which may increase biosimilar use in Germany and is, therefore, a positive signal for biosimilar manufacturers, as currently there is no indication that specific pricing rules for biosimilars will be implemented.
Conclusion
The EU is a pioneer in biosimilar authorization; however, the degree of implementation and uptake at a national and regional level significantly impacts biosimilar penetration in the individual European markets, meaning that the full benefits of biosimilars are yet to be realized. Positive trends are observed in Italy, where biosimilar uptake is steadily rising and Germany and France, where new laws on automatic substitution could increase biosimilar use. In Spain, a generics and biosimilar plan is currently under review by the autonomous regions, and its implementation could lead to new incentives for biosimilar uptake being introduced. However, the actual impact of such laws and regulations will need to be evaluated after their enactment. In the UK, a strong increase in biosimilar uptake was recorded in the last few years; however, uptake of some molecules is highly varying across NHS Trusts.
Before launching a biosimilar in Europe, manufacturers should thoroughly assess measures in place that may facilitate or impede a successful market entry. Strategic evaluation of the advantages and disadvantages of each market, early in product launch planning, is highly recommended along with consulting and educating relevant stakeholders, to maximize the potential for biosimilars in the individual European markets.
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