Activities Driving Biosimilar Uptake in Europe
Welcome to Morbus & Curis, a blog about disease and healthcare. Today’s blog post takes a look at drivers of biosimilar uptake in Europe.
Biosimilars offer the potential for healthcare systems to make cost savings and improve patient access to biologic medicines. Despite this, their uptake is varied across European markets and therapeutic areas.
Let’s take a look at some of the mechanisms, activities and policies that have played a role in driving their uptake across European markets.
Price Controls
Many payers and healthcare systems across Europe set fixed discounts for biosimilars or determine maximum prices through external price referencing.
Although price controls may ensure the potential for a certain size of cost-saving, across Europe there is not a strong correlation between biosimilar discounting and uptake. One reason for this could be that physicians are unaware of their pricing or are less sensitive to pricing, and primarily base prescribing decisions around clinical considerations and guaranteed reimbursement. However, experience with and confidence in biosimilars is also likely to have an impact.
Also, while mandatory price discounts can increase short term savings on biologic medicine spending, they can also deter some biosimilar manufacturers, particularly in markets with lower pricing where the ability to gain a return on investment is more limited. In some cases, this can result in a biosimilar not being launched in a market.
Tendering
Tendering is a common procurement practice across Europe, particularly in the hospital setting, where many biosimilars are prescribed and administered.
Tenders normally grant the supply of a biologic to the manufacturer with the lowest bid and proven capacity to supply. Across Europe, there is some variance in how tenders are prepared with some markets using brand names, whiles others use international non-proprietary names (INN) or therapeutic class.
In the extreme, tenders can give contracts for the supply of a medicine for an entire public healthcare system for one year. This is the case in Norway where the pharmaceutical division of the Norwegian Hospital Procurement Trust (legemiddelinnkjøpssamarbeid, LIS) announces an annual tender for infliximab.
With such a large contract up for grabs, biosimilar discounting exceeded expectations and many watching the biosimilar space were surprised as LIS attained a 69% and 60% discount for biosimilar infliximab versus the originator in 2015 and 2016, respectively.
As the tender is for the countrywide supply of infliximab, following the 2015 and 2016 tender results all treatment naïve patients were initiated on the biosimilar and most patients already receiving treatment with the originator biologic were switched to the biosimilar. Consequently, physicians in Norway became familiar with biosimilar infliximab very quickly and by April 2016 it had a 92.9% market share.
Reimbursement
Due to the high cost of biologic medicines, reimbursement is a key factor influencing biosimilar uptake. A physician is unlikely to prescribe a high-cost product to a patient if it is not reimbursed and reimbursed alternatives that are clinically undifferentiated are available.
While most European countries grant reimbursement for all approved indications of a biosimilar some restrict reimbursement to only the indications included in the biosimilar’s phase III clinical trials. This can limit adoption in the indications that are not reimbursed.
Additionally, even if reimbursement is approved, the level of reimbursement may be restricted. This is often the case in countries that use internal referencing pricing, where a reimbursement level is established for a group of products (e.g. the originator biologic and biosimilars referencing it). This reimbursement limit is often the average price for the group, which negatively impacts uptake of the higher cost versions in a reference group.
Lastly, the use of reference price groups for biosimilars is interesting because it implies that they are clinically undifferentiated and interchangeable, which could impact physician perceptions in markets using them.
Prescription Budgets or Quotas
Prescription budgets and quotas are widespread in Europe. They often require that a certain percentage of prescriptions for a biologic are for biosimilar versions but they can also restrict prescriptions for the originator biologic. They are most effective when robust monitoring is in place so that adherence can be checked.
Financial Incentives
Financial incentives to drive biosimilar uptake are varied across Europe. They are more commonly found in countries that assign prescription budgets or quotas. Some research has reported that their enforcement has been limited or not documented.
Here are some incentive examples from across the continent:
In Germany, financial incentives exist in the form of gain-sharing arrangements, whereby savings attained through biosimilar prescribing are split between Statutory Health Insurance Funds and the prescribing physician.
In the UK, incentives linked to biosimilar utilisation targets of 80% were implemented under a Commissioning for Quality and Innovation (CQUIN) framework. This helped providers attain 80% uptake of biosimilar rituximab and trastuzumab 10 and 8 months post-launch respectively.
In France, supplementary remuneration encourages physicians to prescribe 20% biosimilar insulin glargine in ambulatory care.
Policies or Guidelines
Many European policies or guidelines recommend that physicians prescribe biosimilars for treatment-naïve patients or switch existing patients when biosimilars offer cost savings.
For example:
In Norway, products are ranked according to price and physicians must follow the ranks assigned to products during prescription decision making (except where clinical reasons justify the use of a higher cost/ranked product).
In Austria, physicians are directed to prescribe the most cost-effective product when several therapy options are available.
In the UK, a commissioning framework for biological medicines was issued stating: “Our aim is that at least 90% of new patients will be prescribed the best value biological medicine within 3 months of the launch of a biosimilar medicine, and at least 80% of existing patients within 12 months, or sooner if possible.”
INN Prescribing and Automatic Substitution
Unlike generic medicines, where INN prescribing is mandatory or encouraged and automatic substitution is allowed, this is less common practice for biologic medicines. However, as confidence in biosimilars grow more markets are beginning to permit automatic substitution for biologic medicines in certain circumstances. Here are some examples:
In Poland, INN prescribing and automatic substitution is permitted for biologics since Polish law does not differentiate between generics and biosimilars. Accordingly, mechanisms that have long driven generic uptake there also apply to biosimilars.
France has legalised automatic substitution from a reference product to its biosimilar for treatment naïve patients as well as treatment-initiated patients with the same biosimilar. However, substitution will not be permitted if the prescription is marked as non-substitutable and the law has not yet been implemented.
Germany and Sweden permit automatic substitution if the same manufacturer produces the reference biologic and a biosimilar. Germany also permits substitution for bioidenticals - biologics produced by the same manufacturer and manufacturing process but marketed under different trade names (e.g. Remsima® and Inflectra®).
In Latvia it is mandatory for the pharmacist to inform a patient about the cheapest alternative and substitution is permitted. Patients can refuse biosimilar substitution but are required to pay the price difference between the biosimilar and the originator biologic. For treatment naïve patients, prescriptions must be written by INN then the pharmacist must dispense the lowest cost reimbursed version of a biologic.
Switching
Switching contributed to Norway’s high and rapid uptake of biosimilar infliximab as described above, where the majority of new patients were switched after the LIS tender was awarded to the biosimilar.
Similar outcomes were observed in other markets where key stakeholders such as physicians, hospitals and regulatory authorities recommended switching patients. For example, biosimilar infliximab market share reached 96% in Denmark and 88% in Finland.
“We have to look at the biosimilar as a biogeneric. In fact, the market has to be like that of generics. Without switching, biosimilars will be out of business.”
Dr. Steinar Madsen of the Norwegian Medicines Agency. Source.
Some European markets have adopted a neutral stance and have neither recommended nor prohibited switching. This is in part due to the belief that switching is the prescribing physician’s responsibility and choice.
Others have applied encouragement or informal pressures to switch to biosimilars if they are lower cost by means of position papers or policies rather than restrict rules. For example, in the UK, it was recommended that providers collaborate with clinicians to develop a switch policy with supporting communications to drive awareness among prescribers.
One reported challenge associated with switching is the close monitoring required following the switch, to ensure there are no efficacy, safety or immunogenicity issues, which can be resource-intensive for healthcare providers.
Electronic Prescribing
Biosimilar uptake can be enhanced by electronic prescribing, which can allow physicians to recall prescriptions then issue new prescriptions for a biosimilar, without needing to see the patient. This was leveraged by one physician in Norway who spent 10 hours changing his patients’ prescriptions and consequently saved approximately $3 million.
Education Campaigns
While knowledge of and experience with biosimilars continues to grow, there is still room for improvement.
To address concerns and promote awareness and acceptance of biosimilars amongst physicians and patients, various education initiatives are underway.
One example is a biosimilar Q&A document issued by the European Commission which is targeted at healthcare professionals and patients. A second example is a guide for nurses handling switching patients (Switch Management Between Similar Biological Medicines: A Communication and Information Guide for Nurses) issued by the European Specialist Nurses Organisation (ESNO).
Other initiatives to improve provider, physician or patient education around biosimilars include scientific conferences, seminars, lectures, surveys and leaflets.
Up to now, there has been a weak correlation between biosimilar uptake and price reduction across Europe indicating that physician perceptions and willingness to prescribe biosimilars are key drivers behind uptake, and that some payers may not yet be willing to drive uptake through strict rules or policies.
Real-World Evidence
To date, real-world evidence from Europe has demonstrated that biosimilars are safe and effective and that switching is not associated with major safety, efficacy or immunogenicity issues.
A well-known trial exploring the safety of switching from an originator biologic to its biosimilar version is the NOR-SWITCH trial funded by the Norwegian government. Data from the open-label extension “showed no difference in safety and efficacy between patients who maintained CT-P13 and patients who switched from originator infliximab to CT-P13, supporting that switching from originator infliximab to CT-P13 is safe and efficacious”.
Real-world evidence can improve physician perceptions around biosimilars since it can provide information about a biosimilar’s efficacy and safety in populations that may not have been included in the biosimilar’s clinical trial or for whom there is limited data.
Concluding Remarks
Understanding drivers of biosimilar uptake is of high importance for healthcare policymakers and budget holders who seek to manage healthcare expenditure for older, off-patent biologics during a period of heightened cost containment measures.
Across Europe, there are a wide range of pricing, reimbursement, procurement and utilisation policies and educational initiatives focused on supporting the uptake of biosimilars, but biosimilar market share varies by market and therapeutic area.
To date, various reports and studies have indicated that education initiatives that improve physician understanding and comfort with biosimilars, as well as incentive policies are important drivers of biosimilar uptake.
Price controls such as mandatory discounts have so far had less impact on uptake and a potential downside to price controls is that they risk discouraging biosimilar manufacturers, which could threaten the sustainability of the biosimilars competition and supply due to the more costly and timely biosimilar development process.
Sources
Key drivers for market penetration of biosimilars in Europe
Policies for biosimilar uptake in Europe: An overview
The Norwegian Biosimilar Phenomenon: From Biosimilar To "Biogeneric"
Biosimilars in the UK: where are we now and where does the NHS want to go?
Lessons for the United States from Europe’s Biosimilar Experience By Alex Brill and Christy Robinson
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Cover photo credit: Photo by National Cancer Institute on Unsplash