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Biosimilars and Brexit: What’s in store for UK’s biosimilar market?

pharmafile | June 2, 2021 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | biosimilars, brexit

It’s been 15 years since the first biosimilar entered the market, and the impact of these drugs on the healthcare industry has been immense. Now the UK has officially left the EU, what effect will Brexit have on the booming biosimilar market in the UK? Kat Jenkins takes a look at the new regulatory landscape post-Brexit, speaking with British Biosimilar Association’s Technical Director, Paul Fleming

Fifteen years ago, Sandoz’s Marketing Authorisation Application (MAA) for Omnitrope was approved by the EMA, becoming the first biosimilar in the world to enter the market. Since then, the biosimilar business has evolved into a billion-dollar industry, capturing 10% of the biologic market value in Europe – 7% of that in the last five years. There are now over 60 biosimilars available in Europe, with uptake in other continents paling in comparison.

The US in particular lags behind in biosimilar uptake, with only 11 biosimilar drugs currently available in their market. Pharmafocus spoke to Dr HoUng Kim, Head of Medical and Marketing Division at Celltrion Healthcare, about the issues surrounding biosimilar uptake in the US. He believes the slow uptake is down to three factors:

Difference in patent landscapes, with some EU patents ending earlier and some originator companies generating more patent barriers in the US
The FDA requirement that biosimilars must prove ‘interchangeability’ with the originator before pharmacy-level substitution is permitted, meaning biosimilar manufacturers must conduct multiple-switch trials to demonstrate that switching between the reference product and the biosimilar poses no greater risk than using the reference product
The complexity and fragmentation of the US healthcare system, with early entrant biosimilars having difficulty competing against the contracting and rebating power of the originator manufacturers

With the EU being a clear vanguard for biosimilar uptake, how will Brexit impact the UK market and how can regulators avoid the pitfalls seen in the US? Paul Fleming, Technical Director of the British Biosimilar Association (BBA), believes the answer lies in market attractiveness.

“The single most important thing is keeping the UK market attractive long term for companies and investments, and the introduction of new medicines. In biosimilars in particular, the total number of market participants does tend to be lower than for traditional generics, primarily due to the much more substantial R&D costs.

“Keeping the market attractive so that new people come in and supplement that number is important, so the whole dynamic of the UK market is not just focused at when the biosimilars market forms at the end of patents.”

Since January 2021, the MHRA has affirmed its new role as an independent regulator and began the implementation of several crucial regulatory changes to help aid the UK’s perception as an ‘attractive market’. The most exciting being the launch of new MAA assessment routes, designed to speed up patient access to more affordable treatment.

It is this access that is key to the success of biosimilars across the UK and on a global scale. The immediate short-term benefits of biosimilar medicines are clear – they can save healthcare providers a huge amount of money. Between 2019-2023 it is estimated that biosimilars could save the global healthcare system a whopping $160 billion. However, it is patient access to treatment that is the clear winner when it comes to long-term benefits. Since the advent of Brexit, the UK has taken big steps towards becoming the front-runner in the biosimilar market, as Fleming explains.

“The MHRA have last week finalised some new guidance on the licencing routes for biosimilars in the UK. Up until now, all products have come to the UK as part of the EMA centralised licencing procedure. Companies will still follow that, all those who are interested in marketing their products in many countries in Europe, but people wouldn’t be developing a biosimilar purely for the UK under that regime.

“What is now available in the UK is a choice for companies, they can either do as they were doing before, and then have an extension of that European licence into the UK, or there is an opportunity, and we think this very positive opportunity, to submit their applications earlier to the UK, and that gives the potential for the price to be licenced first in the UK compared to the rest of Europe. That is definitely UK government’s and the MHRA’s intention. And it’s not just a speed benefit. What we’d be very interested to watch is that it would open the field to a wider range of biosimilars coming to the UK compared to other markets.”

Essentially, the MHRA has decided to step out ahead of the EMA, creating a faster regulatory framework for companies to get their products approved in the UK. This has been done through an updated MAA process with a reduced timeframe for the assessment of ‘high quality’ applications. The process will now take 150 days, compared to the previous 210 days, with the first phase lasting 80 days followed by a 60-day clock-stop period.

The MHRA have also introduced an Innovative Licencing and Access Pathway (ILAP), which also further accelerates the assessment procedure, enabling easier UK market access. Companies can integrate ILAP as soon as non-clinical data is obtained, provided they apply for an Innovation Passport. The Innovation Passport will be granted if the following three criteria are met:

The condition is life-threatening or seriously debilitating or there is a significant patient or public health need
The medicinal product fulfils one or more of the following specific areas: (a) innovative medicines (advanced therapy medicinal product, new chemical or biological entity, or novel drug device combination); (b) repurposed medicines (new indication); (c) medicines for rare diseases; or (d) development aligning with the objectives for UK public health priorities
The medicinal product has the potential to offer benefits to patients

Since the launch of the ILAP in January, more than 10 applications have already been submitted. The UK has also extended launched its own version of the EMA’s rolling review process to expand access beyond that offered by the EU. Unlike the EU, it is open to MAAs for new active substances and biosimilars based on a full dossier, whether or not there is a public health emergency. This procedure has already demonstrated its efficacy in the assessment of the COVID-19 vaccines.

Fleming believes this regulatory diversion from the EU will have many wide-reaching benefits for the biosimilar market in the UK. “This is groundbreaking, these concepts are not brand new, they’ve been discussed within the regulatory and in the scientific community, but the fact that Brexit has happened means that the UK can actually move to the vanguard in terms of implementing and take the lead in the conversation.

“It does give a leadership opportunity for the UK as a country, and you could possibly see that as a way of encouraging companies to increase their investment in the UK, and using that as a platform for taking those products to other markets around the world.

“What we see is real potential upside if the MHRA UK licensing regime becomes more attractive, to encourage development in areas where up to now you mightn’t have had a biosimilar medicine. Something that’s a bit more tailored to patient needs, smaller groups of patients, rare diseases, we think that has the possibility to be one of the new frontiers for biosimilar medicines, not just the big ones – the blockbusters – but also areas of patient need where the total number of patients involved is smaller, but the needs of those patients are equally great.”

What next?

The future looks bright for biosimilars, but more work still needs to be done to ensure the UK’s patients are able to fully reap the rewards as a biosimilar investment hub post-Brexit. In particular, Fleming believes NICE needs to improve their processes to allow for faster guidance, updates, and uptake.

“They are slow in modifying their guidance to recognise that biosimilars are now available and there’s an opportunity to use them earlier in the patient pathway.

“That is still an area that is not as smooth, free flowing as it should be so we’re concentrating more on that now. There are patient benefits that are not being gleamed because NICE is not automatically reviewing its guidance and not taking on board this opportunity to make the biosimilar available, to ensure that patients can receive the benefits earlier in the progression of their disease.”

Aside from regulatory framework, there is much development still to come from the biosimilar market, particularly in therapeutic areas. Over the last 15 years, biosimilar medicines have overcome scepticism and mistrust to enter the market in Europe. However, underrepresented areas in biosimilar medicine, such as therapeutics, are likely to face more uptake resistance as they are not widely used. Therefore, to combat this hesitancy amongst professionals support is needed to help build trust in the product, a successful example of how this can be achieved is with the NHS’ work around Humira (adalimumab).

Before the patent expired on adalimumab, the NHS was spending £400 million a year on this single product. The advent of the Humira caused a ripple effect across the NHS, leading to introductions into best practices, more supported information for prescribers, dispensers, and patients to increase the level of understanding around biosimilar medicines.

Fleming described the shift in attitude towards biosimilars due to the introduction of Humira as “a landmark moment”, saying, “that one product experience was so large in its impact, it really did focus everybody, that we’re now in quite a different world.”

Overall, the next 15 years of biosimilars in the UK is on a lucrative and potentially life-changing path. With MHRA rapid approval processes, ILAP, and continued collaboration between key players such as the NHS, BBA, and NICE, the UK is set to be a hub for biosimilar companies and investment. Most importantly, more patients may be able to gain access to previously unreachable and life-saving treatments, this is the true value of biosimilar medicine.

Kat Jenkins