Cell and gene therapies: Where are we now?
By Nicola Redfern, NJ Redfern Ltd
It’s seven months since I covered the subject of cell and gene therapies (CGTs) in my first column for RARE Revolution and there is so much to update on.
The US Food and Drug Administration (FDA) estimates that by 2025 it will begin to approve 10–20 advanced therapy medicinal products (ATMPs) per year.
The NHS has identified 24 ATMPs in 29 indications (in April 2024) that may go through NICE assessment over the next three years to the end of 2026, and we are seeing multiple companies (both big and small) operating in the space.
In the UK we started 2024 with around 18 ATMPs being discussed by the National Health Service in England, the National Institute for Health and Care Excellence (NICE) and/or the Scottish Medicines Consortium (SMC). For some, conversations have already moved forward, and it is anticipated many may advance and become part of routine clinical practice in the coming months.
So, what have been the main developments that have hit my radar in recent months? (This is a personal reflection and only scrapes the surface!)
1: The UK ATTC network’s report
Biotech funding appears to be on the rise in the first quarter of 2024, which has to be good news for investment in new innovations, and the appointment of a Labour government is definitely resulting in positive noise around the importance of improvements to our NHS, the importance of investment into the UK and, at a more grassroots level, how patients need access to treatment more quickly than in the past.
As reported in January, the UK Advanced Therapy Treatment Centre (ATTC) network (supported by the Cell and Gene Therapy Catapult, the Royal Society of Medicine and Lord James O’Shaughnessy) published a report in December that called for specific actions and focus. (ATTC network | Advanced Therapy Adoption Challenges in the United Kingdom)
The report highlighted five areas of necessary improvement:
• leveraging existing world-leading expertise to enable the UK to be the best place internationally to trial and deliver advanced therapies
• realisation of the value of advanced therapies to ensure that UK patients benefit from the latest cutting-edge health technologies
• investment in supporting workforce and NHS delivery infrastructure to allow the UK to benefit from advanced therapy delivery at scale
• improvements in the use of data system-wide to harmonise the advanced therapies ecosystem
• the creation of a government-led advanced therapy taskforce in 2024 to implement these recommendations and cement advanced therapies as a strategic UK-wide health and life sciences policy priority.
So, what’s happened since? It’s great to know things are moving forward positively on many counts, especially in regard to ongoing work and investment around clinical trials.
In March ongoing funding for the Advanced Therapy Treatment Centres was confirmed, with a main focus on clinical trial acceleration between 2024 and 2028.(ATTC press release | March 2024)
Equally, Kath Bainbridge, as rare disease lead at the Department of Health and Social Care (DHSC), was tasked to look at a working group around services, resources, infrastructure and data collection et cetera. Where this sits in the new Labour government priorities is yet to evolve but at least some preliminary discussions and work have taken place.
In the UK we all need to call on Wes Streeting, the DHSC and the Cell and Gene Therapy Catapult to now drive tangible improvements against all recommendations.
2. Other initiatives
In addition to the ATTC’s call for a task force, we understand that a) a new rare disease taskforce is being discussed by LifeArc; b) the Cell and Gene therapy Collective is calling on people to give evidence and come forward with new recommendations; and c) Public Policy Projects’ (PPP) meeting in London in November will look further at genomics and rare diseases, including the role of CGTs.
Coordination of asks across different organisations that impact the rare disease space is vital. When no treatment option is currently available, or the current standard of care fails to address the underlying cause of the condition, and families face ongoing challenges around their quality of life, and the individuals with the condition still have a shortened life expectancy hanging over them, surely, we have a duty of care as a society to do better and to act faster.
If we don’t align on our priorities as a community and speak with one voice, we will cause confusion and delays as the new government sets its priorities.
3. Other positive milestones
There have been many other things in the news, too. We have seen the indications on some of the CAR-Ts expand and come through earlier in the treatment pathway, therefore they are able to have greater impact for those with the relevant cancers.
Chimeric antigen receptor T-cell therapy (CAR-T) is a type of immunotherapy and a highly complex and innovative treatment.
Wasn’t it exciting to read back in May about the restoration of a girl’s hearing thanks to an investigational gene therapy infused into her ear. The trial is ongoing but already an example of how positive the outcome can be in some scenarios and conditions.(BBC News | Pioneering gene therapy restores UK girl’s hearing)
Researchers at Great Ormond Street Hospital (GOSH), University College London and the Francis Crick Institute have discovered a genetic therapy to reverse large moles caused by congenital melanocytic nevus syndrome.(Great Ormond Street Hospital | Research shows potential for ‘life-transforming’ giant mole reversal therapy)
It was great seeing a gene therapy for severe or moderately severe haemophilia B finally recommended in draft final guidance by NICE at the end of June. This opens the doors for eligible patients who might want it but also marks a step forward from a policy and access point of view as it was confirmed as the first gene therapy to finalise its path through the NICE Single Technology Appraisal (STA) process and to be reimbursed via the Innovative Medicines Fund (IMF).(BBC News | haemophilia B gene therapy)
This is to name but a few. I’m sure I will have missed something significant as there’s lots going on!
Improvements are being reported weekly in the wider arena around how CGTs are manufactured, viral vectors produced, processes standardised, and how CRISPR gene editing may be able to be repeat-administered and hence tackle more complex conditions.
4. It’s not at all easy though
On 21 June The Independent published an article entitled “Gene therapy may cure rare diseases. But drugmakers have few incentives, leaving families desperate”.(Independent article)This is a topic which is receiving significant attention in multiple countries and from many in the patient community. We are seeing declining availability of new innovative products across Europe and the speed at which reimbursement decisions are reached is worsening—facing families with months of uncertainty.
Equally, in the United States an FDA approval receives positive headlines but insurance companies take months to then negotiate and reach conclusions and in many cases families don’t have insurance that supports them. Sadly, often the condition faced is too rare to get as far as the FDA decision.
Here in the UK getting treatments for rare diseases reimbursed through NICE remains a challenge. For example, currently sickle cell and thalassemia patients are still awaiting the outcome of a company’s discussions with NICE and NHS England. The costs of producing the products makes it hard for companies to navigate successfully through NICE’s methodology and thresholds.
NICE admitted back in February, at the BioIndustry Association (BIA) rare disease parliamentary event, that their severity modifier, introduced to try and help the situation, is not being applied as often as had been anticipated. The investigation into why, is still, I believe, to report.
As a community we also await clarification on how care giver utilities are to be considered within NICE’s new methodology. Both of these are important considerations as new CGTs come to market.
Sadly, some disease areas also still struggle clinically and it was immensely disappointing for the Duchenne community to see a gene therapy programme put on hold.
New guidance was issued by the International Society of Cell and Gene Therapy (ISCT) helping educate clinicians on how to differentiate between approved and unproven CGT products and what to do if they have concerns. Having sat on the working group, it is worrying to hear how some families find themselves sold on solutions with little if any evidence, and in some countries pay for unproven treatment options. Sad to think this is even necessary.(ISCT | healthcare provider guide)
Finally, the challenges of good data collection and sharing, long-term follow-up and the availability and utilisation of registries continue.
A fast-moving field
So, in conclusion, there is a lot going on! When CGTs are proven to work, the benefits can be significant for individuals, for their wider support system (families, friends and the cross-functional group of professionals that engage with them) and for a country’s health system and wider economy.
The science and technology are moving fast. We will see further studies report in so many important areas in the months ahead. Data in ophthalmology and on Parkinson’s, diabetes, HIV and asthma are all starting to appear, reminding us that the place of CGTs in routine practice won’t just be in the rare environment. The widening use of this type of technology has to be positive as utilising these therapies at scale will have benefits for all.
That said, as a rare disease community, we need to pull together with common asks and recommendations to ensure their role in the orphan and ultra orphan arena is recognised and prioritised by researchers, industry and governments alike.
To industry colleagues, my ask is that we continue to not only explore the science but also ways to plan, manufacture and commercialise these innovations better and at reduced cost. To readers with the ability to influence decision making, you need to be bold in re-evaluating how society values these innovations if we are all to realise the maximum benefit.
About Nicola
Nicola set up NJ Redfern Ltd in 2022 to enable her to consult, coach and collaborate with other organisations, following her experience at bluebird bio. She has a long history in rare disease and oncology within the pharmaceutical and biotech industry and has worked closely with the Cell and Gene Therapy Catapult and the ATTC network in the UK. She is a member of the International Society of Cell and Gene therapy (ISCT) ethics sub group, contributes to the UK ATMP Engage community and projects, and speaks at various congresses and webinars about the challenges of bringing cell and gene therapies to market.
Nicola is committed to and motivated by ensuring people living with significant health challenges have a choice and are able to access transformative treatment options quickly once science and innovation reaches a point to positively impact their lives. She also believes the UK will be stronger if these new treatments are supported and embraced holistically across our ecosystem.
She can be contacted atnickiredfern@gmail.comor connect with her onLinkedIn.
Editor’s note: We hope to keep you updated on all these initiatives in future articles as things take shape, so watch this space!
