Looking backwards, looking forwards
By Nicola Redfern, NJ Redfern Ltd
Its December already (how did that happen!), so it feels right to reflect on the past year and dare to think forward into 2025.
On a personal note, I’ve learnt lots—supporting work in the Duchenne muscular dystrophy space where exciting options are getting closer to approval and routine use, starting to get to know the mef2C and PCD communities has expanded my insights and understanding of living with different rare diseases, joining the International Society for Patient Engagement Professionals (ISPEP) which isn’t specifically rare but is an amazing community of people committed to sharing insights and adding value in our working world, and much more.
We know there are so many rare conditions out there as predicted numbers of both conditions and more importantly the people impacted by them, grow—genetic testing, registries get set up and different initiatives allow us to diagnose earlier.
Given my background It’s been great to see more cell and gene therapy (C>) approvals both from a regulatory and reimbursement perspective across the globe and hear that the first thalassemia patients have been accepted for CRISPR treatment here in the UK. Did you know that according to the ISCT (international Society of Cell and Gene therapy) global regulatory report1, issued in September, in the first half of 2024 there were 2,848 therapies in the global pipeline. 85 products are under regulatory review globally, of which eight products are in pre-registration phase and 77 products are in Phase III trials. Obviously not all for rare conditions but wow—the amount of research going on is mind blowing. And that’s only C>. Holistically 2024 saw some really transformative treatments approved.
Linking to that, confirmed ongoing investment in the UK Advanced Therapies Treatment Centres network to continue work on clinical trials was also a highlight as retaining and attracting this science and academic achievement here in the UK is important.
But you don’t just want to hear my ramblings, so I’ve reached out to some of my contacts, scoured updates on social media and done some research to shape this month’s content. The below just scrapes the surface of the advances made and challenges that remain.
My thanks and credit to the following for their thoughts and insights: all those I am currently collaborating with, my LinkedIn network and especially Dr Jamie Duckers, clinical lead for rare disease in Wales; Prof Neil Watson, director of innovation – Newcastle upon Tyne Hospitals NHS Foundation Trust; Rosie Lindup, senior policy and public affairs manager, UK Bio Industry Association (BIA); Sheela Upadhyaya, life sciences consultant; Steven Ferguson, director of value and access at IQVIA; Henry Burkitt / Jake Pond, from Oxygen Strategy; Lucy McKay, chief executive officer at Medics4RareDiseases; Mark Flannagan, chief executive of Genetic Alliance, UK
Let’s start with comments from Jamie Duckers as this felt immensely positive and I think will resonate for many regarding what we’d like to see happen across many conditions, and sets the tone for collaboration by sharing specific insights:
What positive changes did you see for the rare diseases’ community in 2024?
“For me working predominantly in cystic fibrosis (CF) it has to be, being part of the journey to adoption of the new CFTR modulator therapies which have been life changing for around 80-85% of the CF population in the UK. They have been a product of the CF community working together (people with CF, their families, CF Trust, healthcare teams, researcher and academics, pharma, NICE, international registries and commissioners). I think CF shows what holistic care can look like as demonstrated by registry data which shows the new median predicted survival in the UK at 64 years—an increase from a previous of 50 years old.”
Was there one change/evolution nationally or internationally that excited you the most?
“Despite the advances in CF treatments for the majority there is still a group 10-15% not eligible and it is amazing to see the efforts to find treatments for this group. Again through international collaboration across all stakeholders within the CF community we are seeing the opening up of nucleic based therapies to address this unmet need. This has involved developing a way we reach these groups within the CF population—such as those from ethnic minorities who have genetic variants that have not been included in clinical trials and who’ve had less opportunity to participate in research, and who historically have had suboptimal outcomes. This approach can be an important lesson for so many rare diseases.”
So what did others highlight?
In the UK
- January started with a commitment through VPAG2 to exploring innovative pricing models signalling an openness to do things differently.
- The summer saw actual utilisation of the Innovative Medicines Fund (IMF)3 for a gene therapy—potentially benefitting up to 250 patients. The hope is this will help ‘pave-the-way’ and set a precedent for others in C> and non-oncology rare disease, to create access for innovative molecules in areas of unmet need.
- Our new UK government has recognised the rare disease action plan4 and given top line reassurances to support.
- The Generation Study led by Genomics England in partnership with the NHS committed to recruit 100,000 newborn babies (with parental consent), whose genomes will be sequenced to facilitate the earlier identification of rare genetic conditions in babies, and to gather data for wider research purposes and to explore the risks and benefits of storing an individual’s genome over their lifetime5.
- The publication of four new Knowledge Summaries about rare disease on GeNotes – the first generic ‘rare disease’ content on this NHS England platform. They include information about rare disease, the diagnostic odyssey, mental health and RD, and the need for patient advocacy groups.
And internationally
- The FDA has issued regulations and guidance documents to establish development programmes designed to save time and reduce the cost of bringing therapies to market for serious conditions and unmet medical needs.
- The newly launched European Rare Diseases Research Alliance (ERDERA) 6 is the largest co-funded partnership ever established in the field of rare disease research and innovation. With an estimated budget of €385.5 million, aiming to unify Europe’s fragmented research efforts under a single framework to accelerate the development of diagnostics and therapies.
ERDERA 101: A Rare Disease Patient Advocacy Initiative7 focused on rare disease education, resources, and policy change. The project seeks to 1) empower patients, by providing them with the tools and knowledge to navigate their healthcare journeys, 2) foster community connections, raising awareness, and advocating for better healthcare policies, 3) create a more supportive environment for patients, 4) collaborate with policymakers to ensure that the unique needs of rare disease patients are considered in health legislation and research funding. They have brought together 178 organisations from public and private sectors so far.
Did anyone else hear about a first ever ‘Undiagnosed Hackathon8 which brought together experts from 28 countries, combined phenotyping and genomic techniques for 48 hours and provided diagnosis to 40% of the previously diagnosed families involved? No idea who led but would love to know more.
What lies ahead in 2025?
When writing this it feels like we are still waiting to fully see how investors, payers, the NHS and industry will respond in practice post the UK October budget and the USA election result. At least our new government has recognised the scale of the crisis in the NHS and increased capital spending to address some of the challenges.
Thankfully the UK rare disease community continues to be strong with a fantastic network of patients, carers, PAGs, clinicians, researchers and industry all collaborating together, and there are individuals across government that are empathetic to our concerns.
The launch of the UK MHRA business plan9 brings hope for improvements. An enhanced Innovative Licensing and Access Pathway (ILAP) will priorities faster review times for the latest cutting-edge medicines. In addition, the introduction of SafetyConnect and RegulatoryConnect should ensure the MHRA can respond effectively to new safety signals throughout the product life cycle, modernise existing management systems and reduce administrative burden for companies. The MHRA is also increasing its support for medical devices and digital health technologies which can have positive impacts in the rare disease arena.
We will also see European HTA10 start to make its mark in 2025. How this will benefit or inhibit reimbursement discussions between industry and those trying to manage a country’s finance is hard to tell. For industry, ensuring regulatory colleagues work more closely with market access and we involve the insights of those living with each condition will be crucial. Let’s hope that over time this reduces the discrepancies shown in EFPIA’s Patients W.A.I.T indicator 2023 survey, published in June 2024.
What else should we be considering as we move forward?
- There is a huge need to educate more broadly—many healthcare professionals have a low-level knowledge and understanding of rare diseases. This is something the industry, in collaboration with patient groups, can help with in a meaningful way. If you aren’t familiar with Medics4Rare Diseases do reach out as they are doing some amazing work in this space.
- Not everything rare is immediately life threatening: past innovations are enabling many to live into teenage and adulthood which is fantastic, making more conditions chronic, which brings a lot of unknowns. GP education and that of wider disciplines in the hospital setting will be critical as we move forward.
- There are new medicines for rare diseases available to patients in the US and Europe which are not available to patients in the UK, and this tragically seems to be getting worse rather than better. We need to change this trajectory.
- The latest EFPIA data11 shows that 47% of non-oncology orphan medicines approved by the EMA had been reimbursed in England between 2019-2022, and 40% in Scotland. This is a decline from 59% and 55% respectively in the previous report. The UK is lagging behind comparable countries, with 85% of new treatments for rare diseases made available in Germany, 68% in France and 51% in Spain.
- In a recent BIA/ABPI member survey (October 2023), 11 out of 18 companies reported that less than 75% of their rare disease pipeline is expected to be launched in the UK over the next five years. Companies cited a number of reasons impacting decisions not to launch a product in the UK, including the low likelihood of a positive reimbursement decision and an unfavourable commercial environment. This is very concerning as we are losing investment and our population is losing out on access to transformative therapies.
- There remains an ongoing debate surrounding NICE’s use of the severity modifier and whether it is bringing the benefits people had anticipated. Continued scrutiny of this process, along with NICE’s upcoming societal preference research on the matter, will be essential.
- Healthcare utilisation and costs in rare disease are often more than many other key areas yet the public and care commissioners don’t appear to be aware—education of decision makers is needed as we are competing with areas such as cancer/diabetes, which have been excellent at raising their profile and of course are in need. If not careful, rare diseases are at risk of being left behind.
- Genetic testing and whole genome sequencing is becoming part of clinical practice which is conceptually a good thing. There is a lot of positive attention on how the UK is leading the way but the detail on how this is operationalised and scrutinised plus the longer-term implications are unclear. Apparently, sector disagreements and bureaucracy are causing delays and uncertainty if one scrapes below the surface. Perhaps an area many of us need to pay more attention to and ask questions about?
- Collection of quality-of-life data in trials for new innovations remains low, funding for the collection of natural history data or insights into life on current standard of care is challenging and the incorporation of lived experience into the scientific plans of companies is patchy at best. All this needs to improve.
- Setting up a new service and ensuring there is equitable access across the country is a critical step as new products get approved by NICE/SMC. The time this takes for industry and the NHS should not be underestimated. Service agreements, training, having the right equipment, communicating to referring clinics are all important steps on the journey before an individual even has the opportunity to discuss and make choices. We haven’t cracked this yet.
New Year’s wish list?
Firstly, I think we are all hoping the UK government will not forget the importance of options and choice for those living with rare diseases as they put their detailed plans in place in the spring. The same will be true across the globe! Recognising that what we learn in the orphan world benefits science and hence the population as a whole is equally critical to shape decision making.
From those asked we’d like to see commitments to the following:
- Stop working in silos and realise that we can share skills and resources across the rare disease community (UK and internationally)
- Ask and involve those with lived experience in any trial design, policy change and service planning,
- Help paint pictures and tell the realities of those living with a condition in all we do. (the good, the bad but also the average day and the routine boring or frustrating bits!)
- Explore the urgent need to accelerate rare disease diagnosis particularly for those who miss the opportunity for new born screening initiatives.
- Capitalise on digital advances, unleashing the power of data and data linkage—without this we struggle to show the burden of rare disease and the need for investment
- Start planning for new services and communicate better to the whole community earlier
- Recognise the importance of real-world evidence and the wider economic impact of living with a rare condition, for the individual and their family, more holistically in all value assessments and decision making.
- Constantly refine and appropriately adapt the ways by which we evaluate new rare disease medicines to ensure we can get treatments to those who need them the most.
- But by equal measure, remember that making a meaningful difference is not just about access to treatments –Metabolic Support UK and Beacon launched a fantastic Living Well campaign calling for ‘Living Well’12 to be embedded as a fifth priority in the UK Rare Disease Framework. An increased focus on a better quality of life overall, including improved support with employment, education, benefits, etc, is critical. Every aspect of the holistic journey a family goes on is important to acknowledge, support and improve.
My thanks to everyone who sent me their thoughts and collaborated on the above. There’s still so much to do together. As Lucy said “Let’s not forget, companies, governments, and thought-leaders will come and go, but it will always be the patient advocacy groups and charities who continue to do the lion share of the work supporting their communities”. Let’s ensure above all we invest in them and fully value their contributions.
So, moving forward Sheela, Michelle, John and I will continue to share our thoughts and insights as we go through 2025. We hope our ponderings give food for thought and help us all connect and collaborate better. Hopefully we will get to see some of you in person at the multiple rare disease activities in February, and the numerous congresses throughout the year.
We wish you, your colleagues, families and friends a peaceful and joyous time over the holiday season that fast approaches. May the New Year bring many magical moments amidst the challenges we all seek to overcome.
References
[1] https://www.isctglobal.org/publications/regulatory-quality-initiatives/regulatory-report
[3] https://www.england.nhs.uk/medicines-2/innovative-medicines-fund/
[5] https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/the-generation-study/
[7] https://www.eurordis.org/erdera-101-explainer/
[8] https://www.undiagnosedhackathon.org/2024
[11] https://efpia.eu/media/vtapbere/efpia-patient-wait-indicator-2024.pdf
[12] https://metabolicsupportuk.org/campaigns-and-insight-2/our-campaigns/living-well/
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 at nickiredfern@gmail.com or connect with her on LinkedIn.
