Attitudes towards biosimilar drugs have rapidly changed in the last 24 months, but there is still work to do. Divya Chadha Manek from the National Institute for Health Research (NIHR) – the research arm of the UK’s National Health Service – takes stock of the British biosimilar journey so far and hints at where we might be heading next.
Uptake and access to biosimilars in the UK’s National Health Service (NHS) has improved considerably over the last two years. There has been a shift in attitude towards the rituximab biosimilars, compared to the struggles that etanercept and infliximab biosimilars have endured in terms of winning over clinical confidence.
So does the future look bright for upcoming biosimilar medicines that have the NHS in their sights? Without a doubt, there is many a keen eye on the development of biosimilar versions of the blockbuster biologic drug adalimumab, which expects to hit NHS shelves in 2019. The competition will be lively as there are reported to be between 15 to 20 companies poised to enter the market with an adalimumab biosimilar when the patent expires in October 2018.
NHS England continues to do an excellent job of championing the cause by bringing together key players in the biosimilar field: life sciences industry, patient groups, health professionals and NICE. And their efforts seem to be paying off. A significant step-change came with the launch of NHS England’s Commissioning Framework for Biological Medicines (Including Biosimilar Medicines) in Autumn 2017. The NHS now has an ambitious target of at least 90% of new patients being prescribed the best value biological medicine within 3 months of launch of a biosimilar medicine, and at least 80% of existing patients being switched within 12 months, or sooner if possible.
Yet despite all this work, uptake of biosimilar medicines across the country continues to be varied. In October 2017 the NIHR brought together stakeholders working within the biosimilars arena. Angela McFarlane, Market Development Director for IQVIA, presented data which showed regional variation in NHS trust conversion to biosimilar versions of infliximab, rituximab and etanercept. Angela commented:
“There is a lot of work to be done in terms of ironing out variation across England and the NHS England Biologicals Framework will be a key platform for this to happen.”
Indeed, there is still much to do to realise the full cost saving benefits of biosimilar medicines throughout the NHS. And much of it boils down to clinical confidence. Patients and clinicians alike need to feel confident that they will experience the same benefit from a biosimilar medication as from an original biologic drug. One way to develop and build that confidence is by conducting clinical studies – including real-world evidence studies – here in the UK. Clinical studies will provide both clinicians and patients with the opportunity to utilise new biosimilar medicines in highly controlled context and to generate reliable clinical evidence.
However, in 2016 it came to light that some global life science companies were overlooking the UK as a destination for biosimilar trials. Conversations revealed that some companies were struggling to generate enough interest from clinicians in the UK – citing that clinicians preferred to work with novel drugs. Further investigations revealed that, in many cases, these companies had been targeting key opinion leaders in larger academic institutions. One global CRO told us:
“We often find that when a sponsor asks us to run a study in the UK they provide us with a list of sites and investigator contacts. But in some cases those contacts may not prove to be the most fruitful; people may have moved jobs, or it may just be that those investigators are based in big research institutions where there is already a lot of similar research taking place and large demands on some patient populations.”
As a result, key opinion leading clinicians decline to participate in the study which could be misinterpreted as apathy for biosimilar medicine trials. However the reality is that the larger NHS/academic institutions, where key opinion leaders tend to be based, make up a fraction of our NHS. The larger portion, made up of multiple types of NHS organisations and NHS service providers, holds enormous potential for biosimilar medicine trials which to date has been largely untapped.
To illuminate that potential, in 2016 the NIHR commenced a scoping exercise of clinical interest within indications that are relevant to biosimilar medicines (cancer, gastroenterology, diabetes, dermatology, rheumatology and ophthalmology). We asked all research-active clinicians across the entire NHS in England for a show of hands if they were interested in delivering trials of biosimilar drugs. The list currently runs at over 800 clinicians and continues to grow. This resource has become a useful tool for companies wishing to cast their clinical investigator net beyond their usual little black book of contacts.
Armed with this knowledge, the NIHR has begun to actively promoting the UK’s research capacity and capabilities to deliver biosimilar medicine trials to overseas life science companies through its “Focus on Biosimilars campaign” (www.nihr.ac.uk/biosimilars). But this cleverly designed campaign isn’t just aimed at the life sciences industry. It’s also a treasure trove of NHS views and opinions on the benefits of bringing biosimilar medicines into the NHS and is therefore a valuable resource for bolstering clinical confidence. Perhaps hearing it from the horse’s mouth will go some way to easing the concerns of those clinicians who are sitting on the fence.
Meanwhile the education efforts continue. The NIHR is planning to introduce a new online training course to raise awareness of biosimilar medicines and their potential benefits to the NHS. Although it will initially be aimed at NIHR staff, this resource is expected to cascade through to research-active NHS professionals who want to know more about biosimilar medicines. This new resource is currently in development and is expected to be launched in summer 2018.
Nonetheless, the reality is that biosimilars are the new kids on the block. Clinical confidence will grow with time and experience. Bringing more biosimilar medicine clinical trials to the UK will certainly contribute towards improving clinical confidence where efficacy and similarity are concerned. However, some key opinion leaders feel that the longitudinal piece of the biosimilar jigsaw is still missing.
They call for more long-term pharmacovigilance studies of biosimilar medicines similar to BADBIR (British Association of Dermatologist Biologic Interventions Register). BADBIR, led from Manchester, is a UK and Eire observational study seeking to assess the long-term safety of biologic treatments for psoriasis. NICE has recommended that all patients in the UK receiving these new therapies for psoriasis should be registered with BADBIR.
Professor Chris Griffiths, Foundation Professor of Dermatology at the University of Manchester and Consultant Dermatologist at Salford Royal NHS Foundation Trust, explains why registries are important:
“I’m a practising dermatologist and, for example, we know that about 30 per cent of the psoriasis patients in my clinic would not be eligible for clinical trials. This might be because they are either too old, have multiple co-morbidities, or on other drugs which would exclude them from taking part in a trial. Yet these are the patients that we are seeing in the real world when we are using biologic and biosimilar drugs to manage psoriasis. It is this group that probably have the highest risk of adverse events. Thus, real world pharmacovigilance registries, such as the BADBIR study allow us to monitor the long-term safety of these life changing medications.
“This kind of monitoring, and the data it creates, gives both patients and clinicians the added assurance that these drugs are going to perform as well in the real world – as safely and as effectively – as we see in the clinical trials. The BADBIR study has been running for 10 years, and now includes three biosimilar drugs alongside originator drugs. We believe very strongly that the biosimilar drugs should be under the same surveillance as the originator molecules.”
The good news is that the UK is a world leader when it comes to real world research. Professor Martin Gibson, Director of the Greater Manchester branch of the NIHR Clinical Research Network, encapsulates the UK’s real world research strengths:
“It’s important to define what we mean by real world research. Real world data is routinely collected clinical information. Real world evidence is distilled from analysing the real world data for example in longitudinal observational studies. In the UK we have invented a third category: real world clinical trials. This is where we run an entire trial using routinely collected clinical data, like we did with the Salford Lung Study.
“The NHS can do all of the above because we have excellent clinical data systems that are becoming more and more linked through the advent of electronic health records and through organisations such as NHS digital. We can also now explore how user-generated information is collected and added to healthcare data to provide even richer longitudinal outcomes that everyone is interested in.
“The NHS is unique because everybody is in it. This means that results we get are generalisable compared to some other healthcare systems where not everybody has the same equality of access to healthcare that we are fortunate to enjoy. This gives us a significant advantage over many other parts of the world.”
Angela McFarlane, IQVIA, agrees: “The UK is the leading real world evidence country in the world. The reason for that is because we have the richest de-identified patient level data set in the world, and of course it’s all in one health system, where every citizen owns a unique NHS number. This is a unique feature which differentiates the UK from the rest of the world in its attractiveness for research and it needs to be capitalised on. Working with the NIHR we hope to bring about a landmark real world evidence study called NHS BioValue which will demonstrate the value of biologics, including biosimilars, in all therapy areas from a patient experience and service impact perspective.”
So what does all this mean for biosimilar medicines uptake in the UK? The hope is that clinical confidence will continue to gather momentum as new biosimilar medicines come to the fore. Clinical research has a key role to play. Whether that is using the NHS as a testbed for new biosimilar medicines, or making the most of the NHS capabilities for long-term post-marketing pharmacovigilance surveillance studies of existing biosimilar drugs. The UK is currently leading Europe in uptake of biosimilar medicines and we have even more to offer.