European biosimilar market: a tremendous opportunity with variable market access constraints
With the recent recommendation of an anti-cancer blockbuster biosimilar by the EMA, the market has the opportunity to soar. Driven by the fierce interest of payors for affordable alternatives to many biologics, national authorities proactively push for biosimilar adoption. To be successful, players must understand the specifics of each market and tailor their strategy accordingly.
The global market opportunity for biosimilars is emerging as a result of three factors. Through 2020, 30 blockbuster biologics, which achieved $109 billion global sales in 2016, face loss of patent exclusivity in at least one major market. In these major markets, regulatory agencies have now defined appropriate regulatory pathways for the approval of new biosimilars. Moreover, the implementation of cost containment practices on the part of governments and insurers has increased demand for such high-quality and less costly versions of blockbuster biologics. Europe dominates the market for biosimilars, but a sharp understanding of specific national attributes is required for players to perform.
EMA has been a pioneer in biosimilars regulation
In the early 2000s, the EMA led the way in establishing regulatory guidelines for the development and assessment of biosimilars, nailing down key principles that have subsequently been adopted worldwide. The EMA regulatory processes’ efficiency is demonstrated by the successful approval of 32 biosimilars already (vs. 10 in the US).
The last update of EMA biosimilar guidelines (2014-2015) attests to its will to evolve in recognition of: technological advances, accumulated experience with marketed products, and availability of new biosimilar targets. The EMA now allows clinical trials conducted outside Europe to be used for biosimilar filing, saving costs of an extra clinical trial for the sponsor. The updated guidance also addresses specific issues to ease the development of complex biosimilars (e.g. monoclonal antibodies), such as the amount of immunogenicity data needed. Furthermore, biosimilar makers can now benefit from EMA’s “Biosimilars Project” which offers free and tailored scientific advice for the development of new targets based on the originators’ data (quality, analytical and functional) in EMA’s possession.
Substitution policies are within the remit of each country
The EMA centralized procedure does not require a switching study to grant approval to biosimilars and substitution policies are within the remit of each European country. Although EMA considers approved biosimilars as equivalent therapeutics alternatives to biologics, automatic substitution is not routinely performed, mainly due to concerns regarding traceability and to the potential impact of repeated switching on immunogenicity. In some countries (UK, Italy, Spain, and Nordics), guidelines or laws prohibit automatic substitution whereas in others (France, Netherlands, Poland, and Baltics), automatic substitution is implemented at the pharmacist or physician level. For biosimilar makers not familiar with European markets, national policies can sometimes be confusing: in Finland and Germany, national authorities (respectively the FIMEA and the Paul-Ehrlich-Institut) consider biosimilars interchangeable with their reference biologicals, however automatic substitution is not included in their current recommendations, which in the end leaves the prescriber with the decision between originator and biosimilar. In this uncertain and quickly evolving environment, biosimilar makers which are able to provide strong switching data have a certain competitive advantage.
Nordic countries are at the forefront of the real-world clinical evidence gathering effort
The initial resistance that followed Europe’s first biosimilar approval in 2006 shows that physicians’ confidence cannot be taken for granted, because of biosimilars’ high complexity and of the stakes for targeted patients. Therefore, payors are aware that forcing biosimilars adoption for cost reasons alone cannot work. Consequently, European countries have been at the forefront of the real-world clinical evidence gathering effort. In Norway, the NOR-SWITCH study has been pivotal in proving biosimilars quality reliability and clinical equivalence with their originators. Funded by the Norwegian Ministry of Health, NOR-SWITCH examined switching from originator infliximab to biosimilar CTP13 in about 500 patients and showed that switching was not inferior to continued treatment with originator. NOR-SWITCH triggered a radical changed in physicians’ perception, spurring the infliximab biosimilar to a market share above 90%.
Policies targeting biologics procurement strongly enhance biosimilars adoption
Backing biosimilars with high quality data is not sufficient to drive uptake. National voluntarist policies are needed at the procurement level. Indeed, despite payors clear benefit from biosimilar usage, there might not be any financial incentives for the hospital, physician or patient to use the biosimilar.
In Nordic countries, the impressive uptake of biosimilars provides sharp insights on the impact of procurement-level strategies. In Norway, epoetins were originally covered by general reimbursement, thus neither the patient nor the physician recognized the biosimilar-associated savings, leading to little switching and low uptake. In 2016, epoetins were transferred to hospital tenders. Two months later, the epoetin biosimilar had gained a 65% market share. This drastic switch was enabled by cost containment awareness among physicians, but also due to an efficient electronic prescription system on which physicians could quickly and massively recall their patients’ prescriptions. In Finland and Denmark, biosimilars also deeply penetrate the biologics market because of strong financial incentives and a management push for biosimilars in hospitals. Opinion leaders often use the NOR-SWITCH study results as a key argument.
Incentives strongly facilitate biosimilars adoption
Tendering at hospital level does not automatically drive biosimilars adoption. Payors must closely monitor the actual adoption at hospital level. For instance, in Ireland and Belgium, although hospitals can procure biologics by competitive tendering, until recently they were indirectly incentivized to purchase the highest price product because they could keep the discount, which are larger for more expensive products. In Spain, some regions such as Madrid have contracts with hospitals to closely monitor the uptake of biosimilars and reward the hospitals that comply with the contract objectives. Prescription quotas can also be installed to force the adoption of biosimilars. In Germany, different prescription minima are set by each regional insurer to promote the use of biosimilars, with physicians being financially threatened for not achieving their objectives. Similar quotas exist in Italy, along with specific education programs designed to foster the use of biosimilars. Consequently, Germany and Italy are now among the top adopters of biosimilars in Europe.
An alignment of positive positions from expert societies, medicine agencies and hospital management, along with financial incentives, is key to fully drive biosimilars adoption. In all countries that enable such collaborations between payors and prescribers, the biosimilars market share is significant. For players, success then strongly depends on their capacity to find the right contracting channel, which is reliant on: the national market structure and clinical practices, and their therapeutic area. Therefore, players must adapt their business models depending on the country-specific market access conditions. But in a market regulated by an agency continually renewing its effort to closely accompany biosimilar makers with an adapted framework, and where 80% of physicians are incentivized to use biosimilars, opportunities cannot be missed.
Information and points of view disclosed in this article are based on Cepton’s knowledge and on the following sources, which we recommend reading:
1. Schiestl M, Zabransky M, Sörgel F. Ten years of biosimilars in Europe: development and evolution of the regulatory pathways. Drug Design, Development and Therapy. 2017;11:1509-1515. doi:10.2147/DDDT.S130318.
2. Scott Morton, Fiona, Ariel Dora Stern, and Scott Stern. “The Impact of the Entry of Biosimilars: Evidence from Europe.” Harvard Business School Working Paper, No. 16-141, June 2016. (Revised July 2017.)
3. Generics and Biosimilars Initiative online resources