The future of biosimilars in the UK

Claire Green summarises highlights from the Westminster Health Forum on biosimilar innovation, regulation, and uptake

About the Author

Claire Green, MRPharmS Editor, Specialised Commissioning

claire.green@mgp.co.uk

A Westminster Health Forum on The future of biosimilars in the UK—innovation, regulation and increasing uptake, was held on 18 October 2018 at Congress Centre, London.

The biosimilar evolution—or revolution

Kavya Gopal, Head of Specialty, Sandoz, and Chair of the British Biosimilars Association discussed how the UK has been a leader in biosimilar uptake.

The UK has seen a consistently strong uptake of biosimilars in the last 3 years, including some very complex biologics in very complex disease states. Infliximab biosimilars, launched in the UK in 2015,¹ are now at 91% uptake in England, according to The Medicines Optimisation Dashboard,² whereas lots of other countries are not at that level. Uptake of biosimilar etanercept is at 82%, and biosimilar rituximab, launched in 2017, is already at 73%.² (Note: these were May 2018 figures; see Figure 1 overleaf for the most recent July 2018 figures.)

The UK has done everything possible to make the uptake of biosimilars work—not just for NHS savings, but from a hospital standpoint, and from a practice standpoint—ensuring that patients continually receive the right care.

Across Europe, biosimilar uptake has not been as rapid because the dynamics in these markets are quite different. Germany and France, for example, are more retail based: patients go to a physician’s office, a product is prescribed, and a pharmacy dispenses it. Italy and Spain are more similar to the UK because they are ‘tender markets’. However, tender markets differ. In Nordic countries, the winner of the tender takes all. The beauty of the way the tenders work in the UK biosimilars market, is that they are frameworks that still allow choice; any of the biosimilars on the framework can be used by hospitals. A hospital then makes a choice of which biosimilar they want to use, and they will actively move all appropriate patients from the originator to the biosimilar. The UK’s positive approach to biosimilars has achieved really good uptake, saving £210 million in 2017/18.³

The UK has done everything possible to make the uptake of biosimilars work … ensuring that patients continually receive the right care.

Increasing complexity

The complexity of biosimilars has changed in the last 10–15 years:

• the more recent biosimilars are much larger products in terms of value, with the originators essentially blockbusters when they launched
• more indications will be coming, in addition to immunology and oncology
• the availability of strong clinical data is of even more importance than it used to be; clinicians need to be comfortable using these products for chronic conditions; for example, if a patient with rheumatoid arthritis is stable on a biologic, clinicians may not want to take the risk of changing their treatment, risking a flare-up in a previously controlled condition, because of the huge impact on quality of life
• there is now significant patient engagement and impact; while some biologics are administered in hospital, many are self-administered by the patient, so patients need to be comfortable with any changes
• the engagement of patient associations and nurses, not just clinicians, and the associated training, is more important now than it was before.

Tools and resources

There are several tools and resources available to help with switching to biosimilars:

• What is a biosimilar medicine?⁴
• Commissioning framework for biological medicines⁵
• The Cancer Vanguard Joint Working Project⁶
• Regional Medicines Optimisation Committees (RMOC) guidance, which is available for some of the new products.

The future for biosimilars

Between now and 2025, some interesting biosimilars will be coming to market for a mix of indications; for example, biosimilars of bevacizumab, pertuzumab, aflibercept, ustekinumab, and denosumab are anticipated. The UK market for these will be interesting because they are not based on big blockbusters like some of the recent biologic patent expirations. Potentially, less clinical data might be required for these products, leading to faster approvals. New formulations beyond the reference medicine may be developed for some biosimilars, e.g. subcutaneous. Finally, it is important to remember that the goal of switching to biosimilars is not just to gain savings for the NHS, or for biosimilar companies to make profits. It is also about increasing access for patients. Savings should be reinvested to improve patient access and NHS sustainability. Therefore, keep an eye out for changes to guidelines, pathways, and the regulatory framework over the next 2–3 years. Earlier access to biologics could mean prevention of long-term complications, leading to further cost-savings beyond just the drug cost.

Savings should be reinvested to improve patient access and NHS sustainability

Learnings from the North

Dr Martin Perry, Consultant Physician and Rheumatologist, NHS Greater Glasgow and Clyde, shared his experiences from a national project in Scotland where he was seconded as a rheumatologist to a group called the Effective Prescribing Programme.

The project was initiated by the Government under a transformational change programme, and the aim was to switch patients from originators to biosimilars across all of the 14 territorial health boards in Scotland. This approach was undertaken because the Government had looked at existing data from Scandinavia and saw that there was considerable difference in the initial phase of biosimilar uptake. For example, in Denmark there was very rapid introduction of biosimilar agents, of almost 96% at 6 months, whereas in Sweden less than 10% of patients were initiated on biosimilars. What were the issues here? Well there were, of course, financial drivers, but in Denmark national advice was distributed, they took clinical consensus, and their national procurement system initiated change. In Sweden, however, the drug authority had quite a negative approach, they decided not to recommend switching, and there was very low managerial involvement.

Implementation in Scotland

• Firstly, a series of workshops was initiated. These were specialty based, it was an iterative process, and the same clinicians and a broad selection of stakeholders were involved over a period of time to ensure a thorough understanding of the existing framework
• Secondly, each of the biologic leads for all the health boards was approached. Dr Perry or his gastroenterology-seconded colleague got in touch with the leads to try and understand what the local barriers were to implementation and to facilitate change
• Thirdly, the national procurement agency developed a monthly report that outlined biosimilar uptake and originator molecule uptake in each of the territorial health boards. These were distributed to all the chief executives and biologic leads and several of them said that this was a spur to help them facilitate change because they were comparing their rates with other areas
• The fourth area was to develop publications at both at a grassroots level and at a national level. Case studies were identified where switching had been effective. The case studies included the business cases, quality, and drug monitoring. Nationally, a policy document was developed—A national prescribing framework—which was intended both to educate and reassure.⁷ This set out broad principles of prescribing, in addition to a lot of practical advice about switching process
• Finally, a system of biologic drug monitoring was piloted to ensure quality of care. This was put as a business case to the chief executives of all the health boards. They accepted it, and in March 2018, a national service was started for measuring serum blood levels of two biologic drugs, with plans to extend it further.

The importance of patient engagement

To a patient there’s no immediate benefit in switching to a biosimilar drug, so this can be a tricky area. They don’t necessarily see a difference, and there can be a perception that moving to a cheaper drug implies lower quality. The way in which the team engages with patients is crucial, and the more face-to-face contact that can happen as part of the informed consent process, the better. Patients are mostly happy to switch once the process has been explained clearly, both face to face and with some written documentation.

Gain-share arrangements

There is a gain-share issue, but such arrangements can work. For clinicians, there is a real hassle factor with switching: they need to identify patients, change prescriptions, engage with patients, and spend time making sure they are happy with the process. Surprisingly, the NHS managers involved were very engaged in looking at the gain share and this resulted in very supportive gain-share arrangements. For example, a locally gained pharmacist and specialist nurse.

Conclusions

The learning points identified through clinician engagement and the implementation of national strategies were key. Cross-specialty working and co-operation helped yield success; the integration of gastroenterology and rheumatology led to services and developments that wouldn’t have happened otherwise. Finally, the local gain share and managerial buy-in were key to getting clinicians involved. As a result, targets for biosimilar switching were exceeded fairly rapidly and uptake of biosimilars has increased in rapidity as each new agent has come out.

Cancer vanguard biosimilars project

Jatinder Harchowal, Chief Pharmacist, The Royal Marsden NHS Foundation Trust and Medicines Lead for the RM Partners Cancer Alliance, shared his experience of the introduction of biosimilars in the Cancer Vanguard.

The Cancer Vanguard combined local and national expertise from three very large cancer centres to create a programme that aimed to improve biosimilar uptake, and reduce variation, across the country. The idea was to produce something that everybody could download, utilise, and adapt for their local practice (see Figure 2).⁶

The initiative ran from 2016 to the end of March 2018. An interactive online PDF was produced, detailing all the work needed to prepare for a biosimilar switch, starting from 6 months before switch.

Key learnings

• Education and information on biosimilars is key
• Don’t underestimate how important it is to engage with clinicians and patients, including patient groups
• Commissioning guidance and commissioning for quality and innovation (CQUIN) enablers help with uptake
• Engagement with commissioners throughout is important, to make sure that people are either incentivised or the savings go back to the NHS
• Replicability of approach for different biologics
• Non-promotional support from pharmaceutical companies helps with scaling up educational materials.

The widespread support for biosimilars that is around now was not there 18 months ago. Colleagues in other countries paint a picture that shows where the UK was 2 years ago. There are people around the world who can share and learn from this experience.

Realising the potential of biosimilars

Marjan Noor, Partner at Allen & Overy, explained how the regulatory framework for biosimilars will continue to help the UK realise its potential.

One of the reasons Europe is so advanced compared with America in the regulation of biosimilars is that the legislation was overhauled in the mid‑2000s. There was an introduction into the legislation of a specific provision to allow for biosimilar approval. For the first time, legislators recognised that biosimilars were different to small molecule drugs, and that biosimilar companies could never show that their product was exactly the same as the originator. A system had to be put in place to allow a more simplified approval, but not necessarily needing to establish the same level of identity as with a generic medicine.

The European Medicines Agency (EMA) produced guidance on what sort of pre-clinical and clinical studies companies would need to submit in order to get biosimilar approvals. They produced a quality guideline, a non-clinical and clinical issues guideline, and probably most importantly, a series of product-specific guidelines.

Part of the reason the antibody biosimilars came later was because the antibody approved product-specific guidelines came later. The original guidelines were for more simple molecules, for which it was easier to establish exactly what tests were needed to demonstrate biosimilarity. As the EMA and companies became more confident in terms of the amount of data that needed to be submitted, more product-specific guidelines were developed.

Biobetters

If a company seeks to improve a biosimilar and makes adjustments to it that are considered innovative, then that product, a ‘biobetter’, can get a patent in its own right (provided that the patent for the original biologic has expired). There are advantages in doing this because although the burden of bringing a biobetter onto the market is less than with a completely new originator product, it attracts an exclusivity advantage if it can get patent protection to prevent other companies from launching biosimilars of the biobetter.

Balancing the biosimilars NHS financial windfall with improved patient access

Angela McFarlane, Market Development Director, IQVIA offers a post-conference update on the biosimilars market and explains how a sustainable market can be created that balances innovation with value.

The UK is second to the Netherlands with regard to the uptake of biosimilar rituximab (see Figure 3). The data for trastuzumab for breast cancer is just starting to come in as the most recent biosimilars enter the market, but the trajectory bodes well for another windfall. For infliximab biosimilars for inflammatory conditions such as rheumatoid arthritis, Crohn’s disease, psoriasis, and ulcerative colitis, the UK is behind Denmark, Norway, and Poland. For etanercept, again for inflammatory conditions, the UK is third in the league table after the Scandinavian countries. At the time of writing, it is too early to report on adalimumab biosimilar data.

Use of purchasing mechanisms

Careful design of the purchasing system is needed to balance the effectiveness of tenders and contracts with the requirements for long-term market sustainability. Tendering and contracting in the biologics market can, if properly balanced, facilitate the generation of healthy market competition, allow adequate management of healthcare budgets over time, and address the needs of key market stakeholders (patients, physicians, care institutions, biosimilar manufacturers, and originator manufacturers).

Insights on the adalimumab tender

The most recent tender carried out for adalimumab has taken on board some of the issues raised in IQVIA’s 2018 white paper about creating a competitive and sustainable market.⁸ In order to allocate market access fairly and start to develop a sustainable market, the available English market was split into 11 regional groups of providers, varying in size and based on the location of the hospital provider. This meant that no one supplier of adalimumab could be awarded the whole market, and it provided a strong incentive for suppliers to offer their best price at the point of tender. NHS England intends to set a reference price for adalimumab, applying from 1 April 2019, which commissioners and trusts will be expected to use.

Pricing control policies

Price control policies in the form of molecule reference pricing, direct price cuts, or other forms, facilitate budget release in the short term while granting access to the biologics markets for all biosimilar and originator players. In parallel, physician prescription freedom is maintained and patient product continuity is guaranteed to a greater extent. Price control should, however, be implemented so that market forces are not significantly disrupted and manufacturers remain able to freely compete based on multiple product criteria, and services beyond price.

Promoting innovation

In an environment that fosters sustainability, both originator biologic and biosimilar manufacturers are incentivised and encouraged to continue innovating in differentiation areas for their products outside price, and to continue the development of new products, further supporting the sustainability of the market and finding new ways to support the needs of all other key stakeholders.

Improving patient access

There is an unmet patient need for earlier use of biologics than the now rather outdated NICE guidance allows. For the real benefit of the disruptive promise that biosimilars hold, it’s time for an honest conversation between the stakeholders, because the UK has the toughest access criteria in Europe. The launch of biosimilars enhances competition within the market, resulting in price reduction of both the originator product and the biosimilars. As price decreases, the cost per quality-adjusted life year (QALY) is also reduced, making these therapies more cost-effective. For example, there is scope for CCGs to have pragmatic, evidence-based discussions with clinicians to allow earlier use of biologics, including biosimilars, within the treatment pathway for rheumatoid arthritis and other inflammatory conditions, to bring the UK standard of care in line with that of the EU5.

The question remains for NHS leaders: do you mean what you say in the Biologics framework about improving patient access and really applying the term ‘best value’? NHS leaders should be pragmatic about the scope for allowing earlier use of biologics, including biosimilars, or does the NHS payer attitude not exist for anything other than recycling the savings to fill local potholes?

References

1. Infliximab biosimilars to launch in the UK as innovator product reaches patent expiry. Pharm J  2015; 294: 7851. www.pharmaceutical-journal.com/news-and-analysis/news-in-brief/infliximab-biosimilars-to-launch-in-the-uk-as-innovator-product-reaches-patent-expiry/20067917.article?firstPass=false (accessed 31 December 2018).
2. NHS Business Services Authority. Medicines optimisation dashboard. apps.nhsbsa.nhs.uk/MOD/AtlasTrustsMedsOp/atlas.html (accessed 31 December 2018).
3. NHS Confederation. What comes into effect in October 2018? www.nhsconfed.org/resources/2018/10/what-comes-into-effect-in-october-2018 (accessed 31 December 2018).
4. NHS England. What is a biosimilar medicine? 2015. Available at: www.england.nhs.uk/wp-content/uploads/2015/09/biosimilar-guide.pdf
5. NHS England. Commissioning framework for biological medicines. Available at: www.england.nhs.uk/wp-content/uploads/2017/09/biosimilar-medicines-commissioning-framework.pdf
6. NHS Cancer Vanguard. Biosimilar adoption process timeline. cancervanguard.nhs.uk/wp-content/uploads/2017/03/121092-Vanguard_iPDF_DR9.pdf (accessed 31 December 2018).
7. Healthcare improvement Scotland. Biosimilar medicines: a national prescribing framework. 2018. Available at: www.healthcareimprovementscotland.org/our_work/technologies_and_medicines/programme_resources/biosimilar_medicines_framework.aspx
8. IQVIA. Biosimilars: who saves? 2018. Available at: www.iqvia.com/locations/united-states/library/white-papers/biosimilars-who-saves