Market Access and Reimbursement Q&A with Nicola Redfern

Could you please introduce yourself?

My name is Nicola Redfern and I am a director at NJ Redfern Limited, offering consultancy and coaching to organizations planning for future launches in the UK. I have decades of experience in the Pharmaceutical industry, mainly focused on rare disease and the cancer arena, and most recently worked for a company that had a licensed gene therapy in Europe. I am also a previous chair of the ABPI ATMP working group.

Most of my experience to date has been with a one-time gene therapy designed with curative intent but I’m rapidly realizing that not all gene and cell therapies are the same so it’s really important we clearly differentiate between approaches and are clear about what outcomes are aspired to as the challenges will be specific by disease area and product.

What are the main challenges facing market access in advanced therapies?

From my perspective, the whole concept in the gene and cell therapy world is very much around how do we get the full value of that proposition recognized? So are people really thinking about the potential curative intent, the lifelong benefits, and, building in all of those costs, and the wider value to both the individual patient and their family members that may be caring for that patient, but also society as a whole. My experience recently is that value is not fully recognized in payer discussions across the whole of Europe, and decision-makers often lack insight into the disease areas and patient communities they are holding in their hands.

Once value is recognized you then need to have discussions on how they will be budgeted and paid for, if new payment models are needed and can be implemented, and, ensure that the service is ready for them.

What are the main considerations for the reimbursement of advanced therapies? And how early into their development should these reimbursement and financial plans be established?

I think it depends on what gene and cell therapies we are talking about. In the UK, if you are in the world of orphan disease, this is recognized by NICE, you impact life expectancy significantly and you then have the opportunity to go down the highly specialized technology pathway, it’s a bit easier, though not an automatic win. But if you’re talking about a gene therapy that is aimed at a prevalent population, especially if it is in adults rather than children, that focuses mainly on enhancing quality of life and easing pressure in the system for the health service and/or within a family, it is more likely the route through standard technology appraisal will be tough. These differences also play out in other countries’ decision-making.

Equally in the UK the thresholds that NICE is expecting companies to price to are almost prohibitive because these are not easy things to make. Considering the total organizational and manufacturing costs for a new company setting up within Europe, or even in a given country, it is not an easy or cheap thing to do. Even larger companies fitting them in with an existing portfolio and team aren’t making significant profits from supporting this type of innovation.

There is a real dichotomy between the costs to an organization to bring these treatments forward to patients and the really exciting science. These therapies are transformative for the people that they have an impact on and their wider families, friends, and environments. Yet, they are still being evaluated the same way as any other medicines which simply, and often sub-optimally, manage a condition day in and day out, and that is a particular sticking point.

In the UK the discount rate NICE use in their long-term modeling, from a health economics point of view, is 3.5%. This is despite the fact that the Treasury Green Book said that in a health scenario 1.5% was the right way forward, and, that NICE themselves recognized during the methodology consultation that there is strong evidence to move to a 1.5% discount rate. Despite this, it has not yet been implemented. It is very rare that a NICE committee applies the 1.5% discount rate today. When they do, it often results in lots of debate and delays. I think that it is tragic because you’ve got new therapies coming through, being recognized as effective and safe by the regulators, hitting hurdles because the value proposition scenario has not been fully addressed yet. Their potential impact and reach are massively watered down by using the 3.5% discount rate, and that just feels wrong.

The new NICE methodology has come forward containing more flexibilities, and the criteria to get into the highly specialized technology have also changed a little bit. However, there are still multiple gene therapies coming forward that will struggle if the 3.5% discount rate is applied. Small companies especially are really going to struggle to bring them to market in the UK.

This was definitely what we saw at bluebird bio. bluebird made the decision to withdraw from Europe, which also impacts the UK, – UK patients and UK clinical trials. Being in the single technology appraisal at a 3.5% discount rate in the health economics modeling was one of the big factors that made it prohibitive for bluebird in the UK.

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Regulatory considerations and what are the main barriers to regulations of advanced therapies in Europe?

I think that the European regulators, the EMEA, have embraced the uncertainty and the lack of long-term data that comes with the type of treatment this is, and have actually been prepared to review small data sets and give conditional approvals in order for these things to get to the patient community quicker – because they recognize that transformative nature of what’s going on. So personally, I’ve seen the regulators try very hard to be more proactive and more engaging in the discussions early from an efficacy and safety perspective.

Often there are no effective treatments for the diseases that these therapies are targeting, and therefore the unmet need and the benefits that gene and cell therapies can bring are massive. The EMEA was brave. They were forward-looking, and very patient-centric in moving forwards with gene and cell therapies quickly. I think in the UK the mutual recognition agreements (MRA) are slightly hampered by the Brexit situation and they are still partly in catch-up mode with getting organized. But, I think they are equally being forward-looking and optimistic and want to be the best in class. We’ve seen that with the introduction of the innovative, Licensing and Access Pathway (ILAP) passport, which recognizes innovation and is definitely encouraging conversations between industry regulators and payers much earlier.

We should be introducing reimbursement plans as early as possible in my books. Almost all companies need to get better at looking at what is the value proposition. It is likely that you don’t fully know this value at the start of development, you just have a hypothesis. That said, given we know how different countries evaluate value today, (I’m not saying that’s the right way to do it), how do we as individual companies ensure that we cannot just manufacture, but manufacture and produce all of the parts that go into the mix, at a price that the payers are then going to recognize.

For me, that isn’t about giving up on changing the system and just accepting the status quo. I think it’s a given that we have to continue the conversations actively around how we define value for potentially curative treatments and for new innovations that have a life-changing impacts on quality of life and life expectancy. How do we reshape the whole paradigm? How do we set the services up in order to be ready for a very new paradigm? The science is there and we’re now at this milestone where we can potentially cure things, so we need the whole community to look at how we can ensure that happens.

I think that the ILAP, conceptually, should help that on its journey. It should help to identify for small biotechs starting out, what the hurdles are and give them an open door to communicate with all of the relevant stakeholders. This will help them look at how do they optimize their manufacturing? Where do they set their offices up? At what point to build their teams out? What footprint do they really want and need? And also, how to educate the pharmacy departments, the nurses, the Doctors, and all of the different people who will touch on this before the point of getting it to the families that need it and want it. So the ILAP should be exciting. However, I am slightly skeptical as to whether it is going to happen in practice. It is early doors for this program and I’m not quite clear, after having been involved in the pilot while I was at bluebird bio, how it is going to pull through to fruition, and whether it’s really going to make a difference unless we change how value is defined. Although we are engaging earlier we are still hitting the same hurdles later on.

What are some of the barriers to the ILAP?

I’ve not been close to the program for the last six months. I had questions last year when it was all starting out as to how engaged NHS England and NICE were in the process. In the beginning, I was optimistic that perhaps the NICE methodology would change more than it did. If we saw more evolution in the discussions on the discount rate with NICE, and they ensured that upon gaining an ILAP passport, conversations about routing to the right pathway were part of those really early discussions, then it’s got great potential. I’m just not convinced through talking to people that it is necessarily going to pull through.

How important is it to build strong relationships between biotechs, manufacturers, regulators, and reimbursors?

On a personal level, I found that the senior people leading the ILAP scheme at the EMEA were all very approachable, so I think the industry should be confident in reaching out to them. I think they are open to having some really honest and transparent conversations early on. I think in the UK we probably have more accessible conversations with some of those people than you do in other European countries. If you are a biotech in the US thinking about Europe and what you’re going to do, reach out and come and chat.

Don’t be mistaken and think Europe’s all the same because it is very different country by country and even within the context of the UK. The conversations in Scotland and Wales can be different than they are in England, and Northern Ireland again. If you’re a US biotech, or a biotech start-up, thinking about working in Europe, you’ve got to look at every European country individually and plan for that. It’s really important to bring local expertise and insight into your discussions. The earlier you have those conversations, the better,

But we need to be really cautious that we’re not overly optimistic about how quickly we can change things and we have to have those honest conversations very transparently and early on before we raise expectations within the patient community. These are potential treatments that are massively transforming, and, we as an industry, involve the patient community really early. We expect families to come forward and be involved in trials and take that risk and go on that journey with us as we investigate the science. But in doing that, we’re giving them hope that something’s actually going to get to market. We’re raising expectations, and therefore across the whole community, we’ve got a responsibility to make sure it can happen.

I don’t think that responsibility sits with one individual company. I think that sits with every company that touches the pathway in the development and the commercialization. That responsibility also sits, in the UK, at number 10, and anybody that reports into number 10. Boris stood on the steps of Downing Street in week one and said we want to get these transformative treatments to patients in the UK, and yet very little tangibly has changed around how we define value and how these treatments are financed. I know it is a slow process sometimes, and I know we’ve had COVID in the middle and you can’t underestimate the impact of that, especially on the NHS, but now is the time. If you look at the pipeline and you look at the number of gene and cell therapies that are coming through in the next five years, and you stop and think about how many families that impacts and how many different diseases can potentially have significantly longer life expectancies and a better quality of life, we’ve got a responsibility to make this happen.

What are some of the differences between market access in the U.S. and Europe?

I think there are differences, but I also think the principles in many ways should be the same.

I think I’m right in saying that the FDA has been slower and perhaps more cautious in approving some of these sorts of treatments. It would be nice to see the FDA take more of a leap of faith in the industry, in science, and in innovation, to move things forward more quickly, because I think they can. From a pricing point of view, once you’ve got regulatory approval, the U.S. seems actually more ready to recognize the total value of the transformation that this sort of treatment brings forward. So yes, you have a slower pace in the U.S. but, perhaps this is a trade-off with the recognition of value being greater.

Ultimately, it is the same objective in the U.S. and Europe – to get this science into clinic and available as a choice for the individual patients routinely.

Do you see that these products are going to be viable down the line in Europe and that the problems with reimbursement are going to be solved?

I think that they have to be solved, I think they have to be embraced, and I think we can’t be too pessimistic. We’ve just had the 10-year anniversary of one of the first patients to be treated with the CAR-T, and there are other disease areas where gene and cell therapies have been approved and are starting to become routinely used. So I don’t think Europe is a complete dead end. For a biotech that is starting out there is definitely an opportunity here, and a willingness from multiple stakeholders to try and make it happen.

I think all stakeholders have got to be realistic about the price. New payment models must evolve to help address the budget impact and ensure that isn’t another hurdle moving forward.

We also need to move from treating short terminal diagnoses in rare diseases, where there are tiny patient numbers and no prevalent population because people have sadly died, into a scenario where we’ve got gene therapies for older patients, where the prevalent population is bigger. This is going to take time. There will be more planning for redesign needed and clinics will have to adapt and think about: How many hospitals do we need to treat these patients? Have we got enough transplant surgeons? Have we got enough specialist nurses? Have we got enough beds in the right parts of the hospital? These are considerations also for when we get to a point where we’ve got multiple gene and cell therapies coming through at the same.

Coming back to how soon do we engage – this is one of the main reasons we need to engage early because the service needs to adapt and be set up, and education and training need to happen so we have people ready to administer these therapies when they get reimbursement. And it needs to be when they get reimbursement, not an if.

I think we have to see the success of cell and gene therapies in Europe, we owe it to the patients, we owe it to society.

From statisticians and biotechs to manufacturers and the people involved in looking at the finance systems and adapting payment models – all of us, whichever bit of it we touch on, have to make this happen because at the end of the day this is in the main about people who’ve been, born with a rare disease they’ve had no control over, that we have had very little ability to impact for decades and now we are at a momentous point in history where change can start to be put into practice. Many organizations in the UK are calling for a new task force to bring efforts and ambitions together. I’d love to see this happen.

I am watching with interest and I think the next five years especially will be a real pivotal time.

Nicola will be speaking about Market Access and Reimbursement at Phacilitate’s Advanced Therapies Europe 2022, taking place between the 31st of August and 1st of September at the Royal Lancaster London.

Find out more about and register your place at Phacilitate’s Advanced Therapies Europe 2022 here >>

For all enquiries please contact Nicola Redfern, NJ Redfern Limited, nickiredfern@gmail.com, 07767323897