How The U.K. Became A Destination For Biosimilar Clinical Trials

By Divya Chadha Manek, National Institute for Health Research (NIHR) Clinical Research Network

The biosimilars market is going to heat up considerably over the next three years, but is the NHS ready for the biosimilars boom?

Let’s set the scene first. The U.K.'s National Health Service deals with over 1 million patients every 36 hours. That’s a lot of patients and a lot of medicines. So, it’s up there with the largest single users and purchasers of all categories of medicines. In 2015/16, the biggest NHS spend on a single drug was the biologic adalimumab (over £416 million). It’s no surprise then, that there are somewhere between 15 and 20 companies either preparing or poised to enter the market with an adalimumab biosimilar when the patent expires in October 2018, at an anticipated significantly lower cost.

With the promise of a smaller price tag than original biologics, biosimilars present a whole raft of prospective benefits for the U.K.’s National Health Service. Potential cost savings may well hold the key to ensuring the sustainability of our globally renowned public healthcare system, while also broadening access to cutting-edge treatments and bringing new hope to patients who don’t quite meet the current biologics prescribing thresholds. Better patient outcomes at a lower cost. What’s not to like?

Evidence Of Change In Acceptance Of Biosimilars

But realizing these benefits requires change. And, as with any change in life, most human beings have to go through a whole internal change management process. Acceptance takes time. So does the diffusion of innovation — early adopters lead the field, with laggards bringing up the rear. Biosimilars have certainly played out this theory in the U.K. Yet despite some initial skepticism, biosimilars in the NHS are well and truly here to stay.

How do we know this? Because attitudes toward and acceptance of biosimilars have rapidly changed in recent years. The NIHR celebrated its 10^th birthday last year, and here at the NIHR Clinical Research Network, the research delivery arm of the NHS, we have access to data about delivery of clinical trials within the NHS, which means we can now gain insight from hindsight.

As a data-rich organization, we have the ability to look back at what was happening a few years ago. And as some of the biosimilar clinical trials that we have supported come to fruition, it has been quite enlightening to delve into the archives.

One of the free services we provide to local and global life sciences companies focuses on delivering feedback from clinical experts on the feasibility and compatibility of proposed study protocols in the NHS environment. When a commercially sponsored study looking at a biosimilar in lymphoma fulfilled its time and target ambition this May, we glanced back at the feedback it had received back in early 2013.

A balanced view came from a one clinician acknowledging that this category of drugs was “significant from a health economic point of view” and thus the study was “important to prove bio-equivalence.” However, this reviewer also commented that biosimilar studies are intrinsically of very little academic interest because they only aim to show equivalence. This would mean that most academic institutions would be reluctant to run these trials, especially “where there are competing academic studies.”

At the more extreme end of the scale, a second clinician reviewer felt the research was “of no interest scientifically” and bordering on “unethical,” stating that they would never offer it to their patients.

Despite this range of views, the study did garner enough interest from U.K. investigators, and it went on to be delivered at four sites in England and met its national target earlier this year. But the issues highlighted at the study level here have also played out on the national stage in the U.K.

Looking Beyond The Usual Suspects

The first issue is what we call “the usual suspects” problem. This is something we have been battling for years for all types of clinical research. This really came to a head in relation to biosimilars in 2015. Despite the U.K. (and Europe) being approximately 10 years ahead of the U.S. in our approach and acceptance of biosimilar drugs, it came to light that some of our life sciences industry partners were overlooking the U.K. as a destination for biosimilar trials. Conversations revealed that some companies were struggling to generate enough interest from clinicians in the U.K., citing that clinicians preferred to work with novel drugs. Further investigations revealed that, in many cases, these companies had, indeed, been targeting key opinion leaders in larger academic institutions. Stephen Jasperse, senior director, investigator and health system relationships, Covance, told me how he too is familiar with this challenge:

“We recognize the issue. These companies approaching the usual suspects in the U.K., in terms of investigators, might not have had the response they expected to their biosimilar study.

“We often find that when a sponsor asks us to run a study in the U.K. 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.”

We received similar feedback from one of the global pharma giants we work with — one of which is at the top end of the top 10 pharmaceutical companies of 2017. A spokesperson revealed that it has had similar experiences:

“I have to say that we have encountered certain challenges in the U.K. when looking to deliver biosimilar trials, particularly in comparison to the rest of Europe, and the main point of that is engaging the investigators. The investigators tend to want to perform research on exciting new novel compounds for their patients, which is understandable, but we really need to engage them and get them excited about biosimilars so that they can help to enhance the options that we have for all of our patients.”

The larger NHS/academic institutions, where key opinion leaders tend to be based, make up a fraction of our NHS. The bigger portion, made up of multiple types of NHS organizations and NHS service providers, holds enormous potential for biosimilar trials — which to date has been largely untapped.

So what have we done about it? In 2016 we commenced a scoping exercise asking all research-active clinicians across the entire NHS for a show of hands if they were interested in delivering trials of biosimilar drugs. The list currently runs at over 600 clinicians and continues to grow — matching the burgeoning biosimilar pipeline in clinical development. The initiative focuses on high-demand areas: oncology, diabetes, gastroenterology, dermatology, musculoskeletal, rheumatology, ophthalmology.

This resource has become a useful selling point for the U.K., in terms of biosimilar research, as companies become more aware of how they can cast their net beyond their usual little black book of contacts. A recent example of this is from Covance, which recently utilized our free site identification service to collect expressions of interest from sites across the NHS in England for a biosimilar trial in rheumatology. Nineteen sites responded positively through the Clinical Research Network’s site identification process within two weeks, whereas the original list of proposed sites yielded limited success. Jasperse explains:

“Our local U.K. team used the NIHR’s site identification service while, at the same time, feasibility was conducted on this original list of 50 potential investigators from our usual sources. From the original list we only got two responses, both of which declined to take part in the study. So that really demonstrates the power of the network approach.”

Building Confidence In Patients, Clinicians

The second issue still playing out on the national stage is the “chicken and egg” challenge, which rotates around awareness, education, and understanding.

Confidence is crucial. Patients and clinicians alike need to feel confident that they will experience the same, or more, benefits from a biosimilar as from an original biologic. These benefits don’t always have to be financial or clinical. The best way to develop and build that confidence is by conducting the studies here in the U.K. and providing clinicians and patients with the opportunity to utilize a biosimilar in the safe context of a clinical trial, to generate reliable clinical evidence.

To combat the chicken and egg challenge, there are a number of things are happening in the U.K. NHS England, an executive public body that oversees the budget, planning, delivery, and day-to-day operation of the commissioning side of the NHS, continues to do an excellent job of bringing together key players in the biosimilar field: life sciences industry, patient groups, health professionals, and, importantly, NICE — the NHS watchdog that approves treatments for use in the NHS and provides guidance on how to deliver them. Guidance for local implementation of biosimilars in the NHS¹ and a new commissioning framework for biological medicines² (including biosimilar medicines) have made the advent of biosimilars official by pointing to successful switching case studies and highlighting important cost savings.

The British Biosimilar Association, representing biosimilar manufacturers in the U.K., is also championing the biosimilar cause, as are relevant health charities and patient groups. Most charities in the key biosimilar therapeutic areas now publish their position or mission statement with regard to biosimilars, and many feature guidance and advice to patients that focuses on education and better awareness of this new breed of biologics.

More recently the NIHR Clinical Research Network has joined the crusade by launching a new campaign that uses engaging video content to promote the U.K.’s research capacity and capabilities to life sciences companies planning biosimilar trials, and to raise awareness of the benefits of biosimilars in clinical and patient communities.³ As the body of clinical evidence grows, so will clinical experience and confidence, consequently breaking the chicken and egg cycle.

And the U.K. certainly has a lot to offer. Alongside its list of ready-and-willing biosimilar investigators, the NIHR published record-breaking performance statistics in August with 73 percent of the commercial clinical trials it supported being delivered on time and on target. Our global pharma company spokesperson agrees that the U.K. is a strong contender on the biosimilar global playing field:

“[Our organization] is very committed to their biologic research, including biosimilars, and certainly the U.K. is a destination where we would want to conduct our clinical research for a number of different reasons. The first one being quality; we certainly have the quality of data here. [Also] the experience that we have within our investigators, their therapeutic knowledge, and certainly the procedures and adherence to the protocols is something we see as very high quality and therefore what we would want to tap into for all our clinical trials whether they are biosimilars or not.”

So, back to the question: “Is the NHS ready for the biosimilars boom?” Yes. I can confidently say it is. I would even go so far as to say change and acceptance are spreading like wildfire within the NHS. The benefits of biosimilars have finally pervaded the psyche of the NHS. Our clinical community is waiting with bated breath to deliver on the clinical trials of these new drugs on the block. Watch this space.

References:

1. https://www.nice.org.uk/guidance/ktt15/resources/biosimilar-medicines-58757954414533
2. https://www.england.nhs.uk/wp-content/uploads/2017/09/biosimilar-medicines-commissioning-framework.pdf
3. https://www.nihr.ac.uk/news-and-events/support-our-campaigns/biosimilars/

About The Author:

Divya Chadha Manek is head of business development (commercial) for the NIHR Clinical Research Network (CRN). Her role is to maintain strategic relationships with global and UK life sciences companies, providing advice and working collaboratively to ensure clinical studies are set up quickly and efficiently — so that they recruit to time and target. Divya also leads on ensuring that the Clinical Research Network is abreast of new study delivery innovations to ensure that the organization is evolving to service life sciences industry requirements.

With a degree in clinical psychology and a master’s in clinical research, Divya has worked with the CRN for the past 10 years. She has experience in clinical research from a site level and from a national perspective in the U.K. Divya can be reached at divya.chadhamanek@nihr.ac.uk.