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Gene therapies: a new age of care in rare diseases?

In April 2023 RARE Revolution hosted a RARE Rev-inar, sponsored by CSL Behring UK, to discuss the impact and potential of gene therapies. The session featured the experienced voices of advocacy leaders and industry experts

By Geoff Case

Samantha Barber, CEO at Gene People
Dan Betts, head of Market Access for UK and Ireland at CSL Behring
Jefferson Courtney, policy and public affairs manager at The Haemophilia Society
Matthew Durdy, CEO at Cell and Gene Therapy Catapult
Nicola Redfern, independent consultant, who collaborates with a number of ATMP industry partners, including CSL Behring
Sheela Upadhyaya, independent life sciences consultant specialising in rare diseases

Gene therapies: where are we now?

There are many thousands of rare conditions, perhaps 10,000 or more.1 Individually these are, of course, rare, but collectively they are common, with approximately 1 in 17 people believed to be affected—approximately 3.5 million people in the UK alone. Most (approximately 80%) of the diseases affecting the rare disease community are genetic,2 and only 5% have any treatment available: 95% do not.3 In both groups there is excitement about the benefits that gene therapies might deliver in the future.

Gene therapies, Matthew Durdy explains, are “medical interventions that aim to change the genetic information of an individual in order to induce an enduring therapeutic outcome”. For conditions that do have treatments, a gene therapy that produces an enduring effect might mean a patient has “a better overall life and perhaps less requirement for medical intervention, and fewer complications,” he says.

Dan Betts acknowledges that the newness of this technology means “we shouldn’t lose sight of the fact that there are uncertainties around long-term safety and efficacy” and says that there are also regulatory, reimbursement and access hurdles to overcome. Still, the ramifications for the rare disease community are potentially enormous. Nicola Redfern says: “We are looking at treatments that could potentially be curative, or if not, extend life expectancy, and/or significantly improve quality of life.” As Samantha Barber explains, “gene therapies give the community hope for the future.”

Jefferson Courtney believes that gene therapies might also bring economic benefits to society in general. Even conditions that have treatments available, such as bleeding disorders, have “a very big impact on the health system”, he says: providing “a very different kind of care to what’s normally expected from the system” comes at a high cost. “Patients need a very wide multidisciplinary team that isn’t just treating the condition itself but the other things that go with it—physiotherapists, obstetricians, gynaecologists, dedicated labs, specialised nurses, specialised consultants…”

He says: “The challenge is demonstrating that it’s important for the health system to provide that care… these diseases are important, and people need to get the care that they need.” Jefferson envisages that if gene therapies for bleeding disorders become available in the future, they may become part of “a menu of treatment options”, so these wider costs would still need to be accounted for.

“There is a need for the healthcare system to understand that the needs of rare disease patients are so much more complex than they are for patients with more prevalent conditions.” – Sheela Upadhyaya

In April 2023 RARE Revolution hosted a RARE Rev-inar, sponsored by CSL Behring UK, to discuss the impact and potential of gene therapies. The session featured the experienced voices of advocacy leaders and industry experts
The reimbursement challenges

The key—and exciting—difference between gene therapies and other therapies, Matthew says, is that there tends to be “a single point or concentrated period of time when the intervention takes place… and an enduring change from that time”. But what needs to be better understood, in his view, is that “a concentration of cost” will result from that.

In England and Wales the National Institute of Health and Care Excellence (NICE) appraises new medicines and makes recommendations for their use within the National Health Service.4 They base their recommendations on a review of the clinical evidence (how well the medicine works) and the economic evidence (how well it works in relation to its cost).4 Nicola believes that NICE tends to be excessively cautious when appraising rare disease treatments and she stresses the importance of decision makers being more flexible in their expectations around clinical and economic evidence.

She explains that the datasets showing how well medicines for rare diseases work are inevitably small because of the rarity of the conditions concerned and says that proving cost-effectiveness is similarly challenging. “It may be that we’ve only got data that covers three, four, five or perhaps ten years—which is not any different from any other treatment that is launched into a market.

“We have gaps, we have uncertainty, we have questions. But when payers and decision makers are looking at these things, that uncertainty seems to be over pronounced, from my perspective. People are very cautious, which is then inhibiting the speed at which these treatments are becoming available for patients and families to make a choice about.”

Many Advanced Therapy Medicinal Products (ATMPs)—medicines based on genes, cells or tissue—have received positive recommendations in NICE appraisals over the last few years,5 but seeing this as “good news” is a simplification, Nicola believes. She highlights how those medicines are for conditions where people have short life expectancies, such as certain cancers, or for ultra rare conditions; and how NICE used its Highly Specialised Technologies (HST) pathway to evaluate these, whereas “increasingly we’re seeing [treatments] for rare diseases routed to the Single Technology Appraisal pathway (STA). People on these committees don’t have the same level of expertise and understanding of rare disease. They’re often trying to review a lot of products on the same day, so they don’t necessarily have the time or headspace to really deep dive into those conditions.”

Dan agrees that the STA route is “less well suited to products for rare diseases with slightly larger populations that find themselves outside the Highly Specialised Technologies route”. Samantha notes that some therapies have been withdrawn before the end of their appraisals; she believes it is important to examine the reasons for that and to reflect on the implications.

“How do we get those NICE committees more up to speed? How do we make sure that the right people are advising the committee? How do we make sure the patient voice is augmented and listened to and taken seriously?” – Nicola

Overcoming the challenges

NICE reviewed its methods for health technology evaluations in 2020. It has recently committed to being more flexible in responding to the uncertainties that arise when generating enough evidence has been difficult.6

“NICE committed to perhaps being a little braver around uncertainty. We’ve still got to see whether that plays out in practice.” – Nicola

Dan would like NICE to accommodate a scientific rationale for evaluating the longer-term safety and durability of medicines when data are limited, rather than waiting—and making patients wait—until longer-term data are available. “I think how that’s incorporated into the HST reviews will be really important for those products that find themselves in the STA process,” he says.

Patients, families and patient groups find the NICE appraisal process difficult, Samantha says. “I’ve personally led a patient organisation through a NICE appraisal. It can feel very hostile because it is an evaluation of cost benefit [cost versus value]… One of the pieces of feedback I got time and time again, from the community was that ‘value’ suggests [there is] a lack of value [to] a person’s life.” The process is also time-intensive, which is especially challenging for the small patient organisations in the rare disease space.

The approval and reimbursement of therapies is by no means the end of the challenges involved in access. Sheela states the importance of coordination between the health and social care system and industry: “We need to be thinking about how we bring things together for us as a country to be well prepared to receive these [therapies] in the volume that we’re hoping to receive them and have the impact that we hope to see.”

Jefferson says: “In areas where there’s high unmet need and a new treatment arises, there must be quicker ways of getting it into the system through things like the Early Access to Medicines Scheme.” He suggests that there could be a move towards collecting more data to add to phase three trial data once therapies are in use within the health system.

Leadership from government is needed to resolve the challenges around access, Jefferson believes. “There isn’t a specific minister or department that is leading on this, across the system. There are people within NHS England and NICE working on it, but [we need] leadership from central government to work out how we bring people together to expedite access to this whole family of treatments.”

Nicola stresses the importance of effective leadership in driving changes to current systems and processes. A “whole-system approach” is needed now that gene therapies appear to be part of the future landscape for many diseases—ultra-rare, rare and common diseases alike. “Trial expectations are mainly the same, regulators expectations are pretty similar… defining value and looking at what’s an acceptable budget impact haven’t really shifted over decades.

“If we don’t take a step back and look at it holistically, it will mean delays, it will mean noes, it will mean pharmaceutical and biotech companies not investing potentially in the UK. And we’re seeing all of those things actually happen already.”

On the other hand, however, she acknowledges that taking a step back and implementing a whole new system will be “clunky” and might cause a loss of momentum. For her, effective leadership means directing the current decision-making groups to be bolder right now. “In the short to medium term, I’d like to see more education of the people who are making decisions. And less caution, more pragmatism, more optimism, so that we don’t slow things down.”

She also stresses the importance of the pharmaceutical industry and biotech industry having a “seat at the table” so that they can collaborate in the process.

“Let’s be less cautious, let’s get more of these things through, let’s see how they evolve in the short to medium term while we look at that bigger picture.” – Nicola


[1] Haendel M, Vasilevsky N, Unni D, et al. How many rare diseases are there? Nat Rev Drug Discov. 2020;19(2):77-78. doi:10.1038/d41573-019-00180-y

[2] England Rare Diseases Action Plan 2023: main report. GOV.UK. Accessed 18 April 2023.

[3] Kaufmann P, Pariser AR, Austin C. From scientific discovery to treatments for rare diseases—the view from the National Center for Advancing Translational Sciences—Office of Rare Diseases Research. Orphanet J Rare Dis. 2018;13(1):196. doi:10.1186/s13023-018-0936-x

[4] Technology appraisal guidance | NICE guidance | Our programmes | What we do | About. NICE. Accessed 12 May 2023.

[5] Technology specific issues task and finish group report. Accessed 12 May 2023.

[6] NICE signals commitment to greater flexibility in its evaluation of promising new health technologies and making patient access fairer | News | News. NICE. Published 20 January 2022. Accessed 12 May 2023.


Date of preparation: June 2023

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