Breaking barriers: Biosimilars

Breaking policy and perceptual barriers: Biosimilars

Experts from Research Partnership analyse the company’s Therapy Watch data to identify how market access policy has impacted the adoption of biosimilars. We ask – what strategies should manufacturers of both biosimilars and originator biologics consider to optimise their brand’s success?

Biologics are big business in Rheumatoid Arthritis (RA), with the first wave of TNF inhibitors Remicade (infliximab), Enbrel (etanercept) and Humira (adalimumab) all having achieved blockbuster sales since their launches in the early 2000s.

In recent years, as patents started to expire, an increasing number of branded and generic pharmaceutical companies have launched biosimilars, offering meaningful discounts relative to the originators – an appealing proposition for strained healthcare systems under pressure to contain costs.

Leveraging over two years of syndicated RA Therapy Watch data* from September 2017-December 2019 in France, Germany, UK, Italy, and Spain, we looked into what parallels could be drawn between country trends in biosimilar prescribing and individual market policies designed to promote their use.

Linking the implementation of policies to changes in the prescribing reality allowed us to compare the effectiveness of different policy instruments at achieving their objectives of realising the potential cost-savings associated with the prescribing of biosimilars over originators.

This leads us to consider what strategies originator manufacturers can employ to break the policy barriers to ensure continued patient access to their branded biologics, and what biosimilar manufacturers can do to break the perceptual barriers to switching to their (potentially) more cost-effective products.

* Therapy Watch is a ‘real-time’ syndicated market tracking tool that provides market researchers, marketing teams and brand managers with strategic and tactical market information using patient record forms

EU5 comparison

A recent snapshot of Therapy Watch data shows the proportion of biosimilar prescriptions in RA based on an aggregation of molecules which have biosimilars currently available. The wide range in penetration of biosimilars across countries is clear. As we delve into the policy context in each market, we can explain these country variations by the uneven application of tools used to encourage biosimilar prescribing.

United Kingdom

The UK has the highest rate of biosimilar adoption. In September 2017, biosimilars already made up over 50% of the share of molecules that had biosimilars available, and their penetration has continued to rise.

Therapy Watch data also provides evidence of switching to biosimilars taking place in practice, with 27% of all UK treatment changes in Q3 2019 being within molecule (i.e. originator to biosimilar, biosimilar to biosimilar, or biosimilar to originator), the highest proportion in the EU5 (France second at 9%).

Despite the UK requiring biologics and biosimilars to be prescribed by brand name, allowing no possibility of automatic substitution at the pharmacy level, multiple policy levers are being employed that can account for this high uptake of biosimilars. First is the NICE recommendation to start treatment with the most cost-effective option – typically a biosimilar. Switching from an originator to a biosimilar is recommended on a case-by-case basis, although there have been pilot projects to enforce controlled switching to biosimilars.

NHS England also aims to incentivise biosimilar uptake through the Commissioning for Quality and Innovation scheme (GE3 Hospital Medicine Optimisation). Providers who adopt “best value” biologic products in 90% of new patients within three months of guidance becoming available, and in 80% of existing patients within one year, receive a bonus of 1% of the contract value for tariff-excluded high-cost drugs.

Procurement is via four regional tenders in England, plus country-level tenders in each of Scotland, Wales and Northern Ireland. Within England, local Clinical Commissioning Groups (CCGs) and hospital Trusts then make joint decisions on which products to prescribe. At this level, there are gain-sharing agreements designed to reward economical prescribing by allowing providers to keep a percentage of the cost savings achieved. Savings are split between the CCG who funds the drug and the Trust that prescribed them.

In parallel, work is being done to break the perceptual barriers to prescribing biologics, with NHS England working on an educational programme to improve confidence and understanding when it comes to appropriate use of biosimilars. The British Society for Rheumatology has also published guidance supporting the managed introduction of biosimilars.

Germany

Data for Germany shows an initial increase followed by a recent plateau in the prescription of biosimilars. As in the UK, biosimilars are exempt from INN (International Nonproprietary Name) prescribing and automatic substitution, but German statutory health insurers and regional physician associations (Kassenärztliche Vereinigunge – KV) have also invested in physician education and implemented quotas. The level of quotas varies between KV, and local administrators can set additional targets, leading to regional variation in biosimilar penetration.

Germany is the best example of applying a ‘carrot-and-stick’ approach to drive uptake. On the ‘carrot’ side, gain-sharing agreements have been implemented by the KV, with physicians who achieve set biosimilar quotas being allowed to bill additional services to their patients. On the ‘stick’ side, prescription patterns are monitored, with penalties for exceeding budget limits at the clinic level. Physicians who exceed their budgets by 125% need to pay the amount in excess of 115% unless they provide justification, further incentivising biologic prescribing as part of a drive to reduce overall spending.

Given the range of measures to promote biosimilar prescribing through both payer policies and physician education, why the plateau in uptake? Strong price competition from originators, through rebate contracts and tenders, may account for some of their continued market share. In reflection of increased price competition from originators, in February 2020, the Federal Joint Committee (G-BA) amended the positioning of their biosimilars policy to say that the physician should correspond to an economic prescription by adjusting the patient to ‘an inexpensive product’ (whether originator or biosimilar). The previous recommendation was simply to prescribe a biosimilar under the assumption the price would be lower.

However, price competition from originators cannot fully explain biosimilars’ plateauing performance; the low rate of in-molecule switching we see (only 3% of all treatment switches) is indicative of lingering hesitancy to prescribe biosimilars, suggesting perceptual barriers remain.

Recognising more had to be done, the G-BA proposed a law in 2018 that would allow automatic substitution of originators with biosimilars by pharmacists. This controversial law currently only applies to ‘bio-identicals’ (e.g. Inflectra and Remsima) but will be reviewed in 2022 and could potentially expand to all biologics.

France

We see a slow trajectory of biosimilar uptake in France when reviewing historic data. This is despite a ministerial framework having been issued in 2017 to promote use of biosimilars including instructions for 70% of outpatient prescriptions to be for biologics.

A small but notable exception to this is infliximab biosimilars, which are more established as a proportion of infliximab use compared to other molecules, despite infliximab being less commonly used in RA overall.

The higher uptake of biosimilar infliximab than etanercept and adalimumab biosimilars could potentially be explained by Remicade being less promoted in the market compared to the other molecules, or their different routes of administration. Infliximab is a hospital product due to its intravenous administration, while etanercept and adalimumab are administered subcutaneously and therefore primarily used in a retail setting.

In the hospital setting, physicians’ prescribing decisions are dependent on what is listed on their hospital formulary. Gain-sharing agreements in place between hospitals and social security encourage the awarding of single-winner tenders to lowest price offers, which can encourage the use of biosimilars.

Given these enforced discounts, and the fact that France is the sole country within the EU5 that allows automatic substitution of biosimilars at the pharmacy level, the low uptake of biosimilars in the retail setting might seem initially surprising. However, there is no incentive for pharmacists to switch. Therefore, despite encouragement and a supportive legal framework, automatic substitution is not being done in practice in RA. With physicians lacking confidence in biosimilars, pharmacists feel uncomfortable with making the switch as the physician is ultimately responsible for anything that may go wrong.

The variation between biosimilar uptake in hospital and retail settings in France provides a stark illustration that where physicians have the freedom to decide between originator and biosimilar, discounts alone will not be sufficient to achieve the desired levels of uptake of biosimilars. As in Germany, perceptual barriers to their prescribing still need to be broken. Meanwhile, originator manufacturers are doing all they can to prolong uncertainty in order to defend their market share.

Italy and Spain

We’ve considered these countries together given their similarly low and sluggish uptake of biosimilars in RA. Across both markets, only just over a third of RA patients who would be eligible for a biosimilar were actually prescribed one. This is despite expected net-level discounts at launch between originator and biosimilar of a minimum of 20% in Italy and around 25-30% in Spain.

The simple explanation is that fewer policies to encourage biosimilar uptake have been implemented. Neither country allows automatic substitution for biosimilars, with no sign this will be permitted in the near future.

The Italian Medicines Agency (AIFA) issued a position paper in April 2018 recommending biosimilars for both treatment naive patients and those patients already treated with an originator biologic for economic reasons. However, its publication has not yet translated into any notable change in the data.

In Spain, the use of biosimilars in new patients is encouraged but switching is not. The ultimate decision is at physicians’ discretion, with the patient needing to consent to any switch. Our data supports the lack of switching to biosimilars taking place in practice, with only 3% of all treatment changes being within molecule.

Compared to other markets, we see more oscillation in the uptake of biosimilars between waves in both countries. The drops are potentially attributable to variation in the discount levels between originator and biosimilar and changes in which manufacturers are awarded the tenders.

Both healthcare systems are highly regionalised, so regional policies are contributing to variation in uptake of biosimilars at a level not shown in the country-level data. Tuscany, for example, set up a tender for infliximab that was won by the biosimilar, Inflectra, with physicians wishing to prescribe the originator Remicade needing to complete a specific form. Some regions have also set biosimilar quotas, but this varies between molecules and regions, and quotas are not binding or strongly enforced.

In Spain, approaches have been introduced in the Madrid region to try and improve uptake of biosimilars since 2010, with specific targets to increase the percentage of new patients on infliximab biosimilars included in 2016.

Momentum to push for stricter policies to encourage biosimilar uptake declined in recent years, with evidence of originators offering price parity with biosimilars. However, in late 2019, the Ministry of Health proposed an action plan to promote use of generics and biosimilars, including fixing lower prices vs. originators and allowing automatic substitution at the pharmacy level. Industry stakeholders have (unsurprisingly) raised strong objections and the current climate of political instability may delay or prevent approval – especially given the broader healthcare challenges Spain faces.

Conclusion

The variation in biosimilar penetration demonstrates that lower price alone is not sufficient to drive high uptake, particularly in patients initiated onto an originator. In general RA treatment terms, physicians resist switching for non-clinical reasons. Patients tend to remain on treatments for years and are generally cautious about switching because if the efficacy is good, they do not want to risk switching. Prescribers’ ongoing resistance to biosimilars is evidenced most strongly by German physicians’ reluctance to prescribe them despite facing potential financial penalties for exceeding their budget.

Strong messaging from originator manufacturers when biosimilars first became available has likely contributed to this hesitation, as marketing teams strived to break the policy barriers to continued prescribing of their products. Company size and budgets are a relevant factor here, with originator companies having put much more money behind marketing than biosimilar manufacturers, which tend to be smaller.

Originators’ efforts have been less successful in the UK, where a longstanding culture of communicating the value of cost savings to the NHS more broadly means physicians tend to be conscious about economic prescribing. However, we still see some resistance to biosimilar use, with higher-priced originators still being used, even here and in the French hospital setting where physicians have to circumvent tenders or miss out on savings for their hospital to continue prescribing them.

Countries with the highest biosimilar use (UK, Germany and France), all have some form of gain-sharing agreement in place. While there are multiple factors contributing to uptake, this could suggest that such agreements have at least some impact in motivating prescribers to use biosimilars, by allowing their practice or hospital to realise some of the associated cost savings.

That said, only legally-enforced automatic substitution at the pharmacy would be able to achieve the most economical prescribing outcomes – but this remains unpalatable across the EU5. It will be interesting to see how the proposed laws in Germany and the draft action plan in Spain develop.

Looking forwards

As the RA market continues to shift away from these molecules towards JAK inhibitors, we are also seeing originator manufacturers increasingly deprioritising their focus on defending their share or being more prepared to compete with biosimilars on cost in order to win tenders. This is likely the case for those originator manufacturers who also have a JAK inhibitor in their portfolio, as they are instead focused on promoting the potential broader health economic savings that can result from their oral administration e.g. less need for nurses and training.

Despite waning competition from originators, it is clear from our data that the perceptual barriers to prescribing biosimilars will continue to be hard to break, especially when it comes to switching patients. In the absence of stricter policy controls, biosimilar manufacturers need to do more to reassure on quality and supply, as well as communicate the positive experience built up since they first became available – as long-term real world experience is the only thing that will fully address some physicians’ uncertainty about interchangeability.

Rachel

Rachel Howard
Director, Market Access

Rachel is currently based in London, having previously lived and worked in the US and Asia. With over 10 years’ experience in pharmaceutical market research, Rachel has extensive experience managing large scale, complex studies, both qualitative and quantitative, with a recent focus on market access and pricing research, including with payers. Rachel’s experience covers many therapy areas, including Rheumatoid Arthritis.

Brett

Brett Gardiner
Director, Market Access

Brett heads up Research Partnership’s specialist market access team. He has managed and contributed to the development of pricing and reimbursement strategies for pharmaceuticals and medical devices in all stages of the product life-cycle across all major European markets, US, Japan, Canada as well as many emerging markets.

Julia-Godfrey

Julia Godfrey,
Research director, Therapy Watch

Julia has 20 years of experience in healthcare research working in RP’s syndicated division for the last 5 years. Julia’s research experience spans all markets and many different therapy areas; however she brings particular expertise in Rheumatology.

Richa

Richa Munjal
Associate director, Therapy Watch

Richa has over 10 years of experience in healthcare and pharmaceutical market research. She has worked on a variety of syndicated and adhoc projects across various therapy areas in all markets. Her areas of expertise include Rheumatology and Hyperlipidaemia.

Research Partnership is the largest independent healthcare market research and consulting agency in the world. We collaborate with clients from the global pharmaceutical, medtech and biotech industries, providing research intelligence and strategic recommendations that elevate healthcare brands and power their success. Our specialist market access service supports the world’s leading manufacturers in market access, pricing, and reimbursement.

To find out more please visit researchpartnership.com/marketaccess

Find out more

Established over 10 years ago, Therapy Watch is a ‘real-time’ syndicated market tracking tool that provides market researchers, marketing teams and brand managers with strategic and tactical market information using patient record forms (PRFs).

To find out more please visit researchpartnership.com/therapywatch