Policy paper

England Rare Diseases Action Plan 2025: main report

Published 28 February 2025

Applies to England

Ministerial foreword

The many people living with the more than 7,000 different rare conditions in England often struggle to access the healthcare they need. This government is deeply committed to turning this around, fixing the NHS and making it work for everyone. There are over 3.5 million people in the UK living with a rare condition and we need to make sure that healthcare professionals are well equipped to recognise and diagnose these conditions and offer people the best possible care. Care needs to be well co-ordinated and delivered as close to home as it possibly can be, and we need to provide rapid, equitable access to approved specialist treatments. 

This action plan is firmly aligned to our 3 health shifts and the work underway on the 10 Year Health Plan for the NHS. Earlier diagnosis helps us shift from treatment to prevention wherever we can as interventions can be given sooner, improving health outcomes in the long term. With better co-ordinated care comes opportunities to shift from hospital to the community. Across the action plan we report on the steps being taken to improve the quality and linkage of data, including through digitalising genomics. We will continue to listen to the voices of those across the rare diseases community as we analyse the responses to our current national conversation on the NHS, Change NHS: help build a health service fit for the future.

This 2025 action plan reports new findings on the inequities that people living with rare conditions face in accessing the health care they need. It is not right that rare can mean forgotten, and this government will strive to change this. 

Over the past 4 years progress has been made, and this action plan transparently reports on progress so the rare diseases community can see both what has been done and what remains to be done. It also enables those working on rare diseases across the health system and in research, regulation and the life sciences sector to work more effectively together to meet our shared goals. 

In this country we have real strengths in rare disease research and we continue to invest through the National Institute for Health and Care Research (NIHR) and UK Research and Innovation (UKRI). Our country leads the world in genomic healthcare and we are forging ahead with innovative approaches to enable earlier diagnosis of rare genetic conditions through initiatives such as the Generation Study and the NHS Genomic Centre of Excellence for Rare and Inherited Genetic Disease.

This is the fourth and final year of the UK Rare Diseases Framework. This year, adding to the 36 actions from previous years, we set out 3 new actions for the year ahead (actions 37 to 39).

The first of these will establish a new model for clinics for multi-system disorders within the NHS, enabling improved and more efficient care for people with rare conditions.

Our second action aims to support rare disease clinical research trials through changes to regulations. We aim to make our country the best place in the world for rare disease clinical research, and make sure we have a regulatory system ready to provide safe access to new treatments as quickly as possible.

Thirdly, we introduce an action to prepare the NHS to deliver groundbreaking, individualised therapies, specifically designed to a unique disease-causing variation in an individual’s DNA, addressing the root cause of the condition. 

As this is the final year of the current UK Rare Diseases Framework, many people will rightly have questions about what will follow. This government will act to drive forward progress on rare diseases as we make improvements in England across the health system and across wider services. Over the next year we will work with our counterparts in Scotland, Wales and Northern Ireland to agree what follows the framework. As we do so we will listen carefully to the voice of the real experts on rare disease: people with lived experience and those who care for them.

Ashley Dalton MP

Parliamentary Under-Secretary of State, Department of Health and Social Care

Executive summary

A rare disease is defined as one which affects less than one in 2,000 people, and there are over 7,000 different rare conditions. One in 17 people are affected by a rare condition at some point in their lives and in total there are over 3.5 million people in the UK living with a rare condition. Although individually rare they are collectively common. Conditions which many people will have heard of include:

• cystic fibrosis
• Huntington’s disease
• sickle cell disease
• vasculitis
• the muscular dystrophies
• Usher syndrome

However, there are many, many others. Sometimes a rare condition affects only one person, or a handful of people, worldwide. 

Many people with rare conditions struggle to access the healthcare they need. The UK Rare Diseases Framework and England’s action plans set out to address this. The 4 priorities of the UK Rare Diseases Framework were identified through the 2019 National Conversation on Rare Diseases:

• faster diagnosis
• increased awareness of rare diseases among healthcare professionals
• better co-ordination of care
• improved access to specialist care, treatment and drugs

Sitting alongside this are 5 underpinning themes on:

• patient voice
• national and international collaboration
• pioneering research
• digital, data and technology
• wider policy alignment

In England we have also introduced a sixth cross-cutting theme of health equity. 

This is the fourth England Rare Diseases Action Plan, published by the Department of Health and Social Care (DHSC), to implement the priorities of the framework. It reports on progress against the previous 36 actions, designed to tackle the priorities and cross-cutting themes of the framework. It also introduces 3 new actions for the year ahead (actions 37 to 39). All actions have been co-developed and are delivered by NHS England and other public sector health partners. 

Throughout the development of our action plans we have listened carefully to the voice of people living with rare conditions to help us focus on addressing the challenges which matter most to them and to develop effective solutions. We are grateful to the patient advisory group convened by Genetic Alliance UK and the UK Rare Diseases Forum for their constructive comments and feedback as we have drafted this action plan. Alongside this our delivery partners have also undertaken their own engagement. 

This action plan aims to report transparently on progress as well as furthering collaboration across people and organisations working on rare diseases. For this reason, we report not only on our actions but also on wider key developments, funded by government and by others, that impact people living with rare disease. 

In this year’s action plan, we first introduce the 3 new actions for the year ahead (actions 37 to 39). To improve co-ordination of care, NHS England is incentivising clinics for multi-system disorders. This will help reduce the number of individual appointments for people living with rare conditions and the burden of co-ordination of care on families. Supporting pioneering research, the Medicines and Healthcare products Regulatory Agency (MHRA) is reforming of clinical trials regulations, including a focus on better supporting rare disease trials. To improve access to specialised medicines, NHS England is introducing an operational framework to support access to individualised therapies for rare conditions. 

Alongside these new actions, we also set out commitments on:

• digitalising genomics
• the NHS Genomic Networks of Excellence on rare and inherited disease
• using existing medicines in new ways to treat rare diseases (including medicines repurposing)
• driving progress on advanced therapies for rare diseases

We also recognise the important role of patient support groups in developing reliable and easy to access information on rare conditions. Building on this, we commit to exploring how the Patient Information Forum’s PIF TICK quality assurance scheme can be used to aid recognition by healthcare professionals of the information patient support groups produce.

In our progress report we focus on ongoing and extended actions from the first 3 action plans. On faster diagnosis we have commissioned research to understand the factors that contribute to the lengthy journey many people with rare conditions face before receiving a final diagnosis. We report progress from Genomics England and NHS England on the Generation Study. This pioneering pilot in the NHS is sequencing the whole genomes of up to 100,000 babies to screen for over 200 rare conditions where an early intervention could alter outcomes. The study has now started recruitment at 24 hospitals across 16 trusts. Finally, NHS England has finalised a service description and provider selection plan for pilot ‘syndromes without a name’ (SWAN) clinics to improve care for people with undiagnosed rare conditions.

On raising awareness of rare conditions with healthcare professionals we report on publication of specific strategies for the nursing and midwifery, pharmacy and primary care workforce through the Genomics Education Programme within NHS England. The programme has also developed a communications tool to aid healthcare professionals in having sensitive conversations, ensuring the patient feels supported in their diagnosis of a rare condition. This has included piloting a virtual reality approach to enable healthcare professionals to practise conversations. We also extend our commitment to mark rare diseases day in the NHS and through this reach as many healthcare professionals as possible, working with Medics4Rare Diseases and Genetic Alliance UK. 

On better co-ordination of care, research is now underway to understand how to improve co-ordination of care in the NHS. Services specifications for patients with rare diseases are now being published that specify requirements for care co-ordination. NHS England has developed service specifications for networked models of care, enabling patients with amyloidosis and inherited metabolic disorders to access care closer to home, avoiding the need to travel. NHS England has also approved 5 new rare disease collaborative networks to improve and better co-ordinate care.

On improved access to specialist care, treatment and drugs, we have worked with industry, clinicians and patients to understand the challenges and opportunities of early access pathways for rare disease therapies. We commit to continuing to keep the effectiveness of the schemes for rare treatments under review. NIHR has made improvements to its Be Part of Research Platform to make it easier for people with rare conditions to use. The National Institute for Health and Care Excellence (NICE) has launched a review of its highly specialised technology programme for evaluating rare disease treatments. 

We also report on progress across the 6 cross-cutting themes. Highlights include work to build on the 2023 UK Rare Diseases Research Landscape report, with workshops with the rare diseases community to understand gaps and priorities. Progress on the new NIHR-Medical Research Council (MRC) funded Rare Disease Research UK platform is reported. This year, NIHR has continued to make significant investments in rare disease research through its HealthTech Research Centres (HRCs). Finally, we publish the results of an NIHR evidence mapping exercise looking at rare diseases and health equity. This reveals more about the inequalities that exist for people living with rare conditions in accessing health services. This exercise will feed in to work to address inequities via the NHS England Core20PLUS Framework.

Over the coming year, we will monitor the delivery of these actions through England’s Rare Diseases Framework Delivery Group, with feedback from the UK Rare Diseases Forum. Work is underway on an evaluation of England’s action plan, with input from the rare disease community on design of metrics. As we look ahead to next steps beyond the current framework we will take account of its findings and continue to engage and listen carefully to the voices of people living with rare conditions and those who care for them.

Introduction

The UK Rare Diseases Framework builds on the 2019 National Conversation on Rare Diseases, which received nearly 6,300 responses. This helped identify the 4 priorities of the framework in tackling rare diseases:

• helping patients get a final diagnosis faster
• increasing awareness of rare diseases among healthcare professionals
• better co-ordination of care
• improving access to specialist care, treatment and drugs

While progress has been made, we know there remains enormous unmet need for people living with rare conditions. This is why this government has reconfirmed our commitment to driving forwards the 4 priorities in the UK Rare Disease Framework, as set out in this year’s England Rare Diseases Action Plan.

This government has a mission to rebuild the NHS to be fit for the future, and we hear from the rare disease community that there are still areas where we need to improve, specifically:

• long waiting times for genomic tests and referrals to the right specialists
• difficulties accessing mental health support
• challenges in pulling research through to new treatments for rare diseases

In the UK, we are lucky to have a strong network of rare disease advocates, healthcare professionals and researchers across life sciences and beyond, committed to driving progress for people living with rare diseases. We’d like to thank the community for their engagement in the development of this action plan, and we remain committed to keeping the voice of lived experience at the heart as a central principle of rare disease policy. We appreciate the work of the Specialised Healthcare Alliance (SHCA) and Genetic Alliance UK, as important umbrella organisations with broad membership, in continuing to advocate for people with rare diseases, and thank them for their recent reports on the UK Rare Diseases Framework and rare disease policy.

The majority of this year’s action plan reports on the progress made against our existing actions, reflecting that many are ongoing. There are 3 named and numbered new actions for the year ahead, and we also describe wider initiatives, funded by government, which are driving forward progress for people living with rare conditions. Reflecting the importance of focusing on the future, we have reversed the order of this year’s action plan, and the new actions appear at the top of the action plan, followed by the progress report.

We will continue to progress all of the actions in this plan. However, we expect that NHS funding decisions for 2025 to 2026 could mean that the pace of progression may change for some actions. At the Budget, the government made nearly £26 billion available to the health and care system over 2 years, with flexibility given to systems as to how they allocate funding while ensuring value for money. Integrated care boards (ICBs), which are now responsible for funding some of the programmes referenced in this plan, may choose to prioritise less specialist services when allocating local budgets. The government will continue to monitor progress closely. Future funding decisions will be made as part of the Chancellor’s Budget in June.

As we approach the final year of the UK Rare Diseases Framework, which is due to close in early 2026, we will continue to build momentum to improve the lives of people living with rare diseases, and work with colleagues in devolved nations to improve care across the UK. In early 2026, we will publish a final paper for England summarising the progress made over the annual action plans, and capturing learning from our commissioned monitoring and evaluation. Learning and evaluation, as well as further engagement with the rare disease community, will form the basis of rare disease policy following the end of the framework.

The 10 Year Health Plan for the NHS

Following the publication of the Darzi review, which set out the state of the nation’s health service, the Secretary of State for Health and Social Care launched the biggest ever conversation about the future of the NHS. This conversation, at ChangeNHS, invited everyone - healthcare professionals and members of the public - to give their views, experiences and ideas that will shape immediate steps and long-term changes in a new 10 Year Health Plan. The 10 Year Health Plan will be built around 3 shifts:

• moving more care from hospitals to communities
• moving from analogue to digital
• moving from sickness to prevention

These shifts will reshape the health system, and in many cases provide opportunities to address challenges that are faced by those who themselves have rare diseases or the people who treat or support them. However, we also acknowledge that some of these shifts are not applicable to every experience of living with a rare disease. For example, many rare diseases cannot be prevented and no disease modifying treatment is available, although early diagnosis and intervention can improve health outcomes or prevent hospital admissions in some cases.

Specialised and highly specialised services (HSS) for rare diseases in most cases need to be delivered in hospital settings to give patients the highest quality care, but in some cases it will be possible to move care close to home to the benefit of both the patient and the NHS. The need for improvements in data connectivity and accessibility while protecting patient data is, however, a challenge broadly recognised across the rare diseases community.

Across the action plan we highlight where interventions are aligned to these shifts, while maintaining the focus on the 4 priorities of the UK Rare Diseases Framework as shaped by the rare diseases community.

Section 1: new actions for the year ahead

Helping patients get a final diagnosis faster

Many people with rare conditions still wait too long for their diagnosis. With an average time to diagnosis of 5.6 years we know that there is more we need to do. We are excited by the progress that is being made through the ground-breaking Generation Study to screen 100,000 newborn babies for genetic conditions where early intervention can improve outcomes. We are seeking to understand more about the diagnostic journey through commissioned research to measure the ‘diagnostic odyssey’ (meaning the often-long period of time it can take for a patient to receive a diagnosis).

While there are no new formal actions under this priority for 2025, we describe below the work underway in digitalising genomics and making the best use of data. It is also important that conditions which do not have an identified genetic cause, sometimes known as ‘non-genetic’ rare diseases, such as autoimmune diseases, also receive final diagnoses faster, and support for people with non-genetic rare conditions is highlighted as a focus area in section 2.

Progress against existing open actions from previous years’ action plans to increase the speed of diagnosis is reported on in section 2. While early diagnosis is important, co-ordinated follow-up care and psychosocial support are vital to enable people to ‘live well’ with a rare disease, and all priorities within the framework must be addressed holistically.

Digitalising genomics

The NHS Genomic Medicine Service (GMS) aims to provide an earlier and more precise diagnosis for individuals with rare disease and allow access to care pathways and support services. Across the coming year, NHS England will progress the NHS Genomics Strategy priority for genomics to be at the forefront of the data and digital revolution, subject to affordability. Supporting the shift from analogue to digital, the NHS Genomics data and digital programme includes 3 workstreams which focus on the development of:

1. Digitalising the National Genomic Test Directory: this will be a suite of cloud-hosted digital services and a published directory of commissioned genomic tests. This underpins and supports all other NHS GMS workstreams, standardises data, supports high-volume testing, and increases accessibility to mainstream test requesters.
2. Electronic test order management system: this will be a new central messaging infrastructure and standardised dataset, to enable interoperability between systems and organisations involved in genomic testing. This will improve test order quality through digitisation and validation, and provide the ability to centrally track orders, store and retrieve result reports in PDF and produce structured report data.
3. Unified genomic record (UGR): this will be individual patient records that are integrated into existing NHS digital systems. A cross-NHS federated data platform and centralised access point will integrate patient genomic data with clinical and other pertinent data in near real-time. This will enable improvements to direct clinical care, research, management information and population health analysis, so increasing testing capacity, reducing patient harm and improving patient and clinical access to data.

NHS Genomic Networks of Excellence on rare and inherited disease

NHS England is currently funding 8 NHS Genomic Networks of Excellence to transform the way in which genomics is delivered across the country, through generating evidence to inform commissioning decisions and developing models for adoption within the NHS. The NHS Genomic Networks of Excellence are partnerships between the NHS, NIHR, academia, the third sector and industry to leverage expertise and resources from the broader genomics ecosystem. The NHS Genomic Networks of Excellence are covering a range of strategic priorities, including:

• prenatal testing
• circulating tumour biomarkers
• haemato-oncology
• rare and inherited diseases
• severe presentation of infectious diseases
• cardiovascular disease
• artificial intelligence
• pharmacogenomics

The Rare and Inherited Disease NHS Genomic Network of Excellence is generating evidence for the adoption of processes, pathways and technology that could revolutionise healthcare for rare and inherited disease patients. This is being done by developing and delivering a sustainable network to accelerate delivery of the clinical and diagnostic ambitions of the UK Rare Diseases Framework for all NHS patients and families affected by rare genetic conditions. This will include developing approaches to offer standardisation across services and sustainable infrastructure to increase diagnostic yield and reduce turnaround times - as well as to improve equitable access to, and efficiency within, diagnostic services in a rare disease clinical and diagnostic laboratory settings.

The Rare and Inherited Disease NHS Genomic Network of Excellence is focusing on exemplars of rapid testing for acutely unwell children, mitochondrial disorders and intellectual disability in adults. The aim is to apply learning across all rare and inherited diseases. This will involve assessing new technologies, analysis and reanalysis strategies as well as supporting access to clinical trials and therapeutics for rare conditions.

Increasing awareness of rare disease among healthcare professionals

People with rare conditions continue to face challenges with awareness of their condition among healthcare professionals. We are pleased to see the progress which has been made, particularly through the NHS England Genomic Education Programme, in developing resources and training for healthcare professionals, which is reported on in section 2. Improving the confidence of healthcare professionals in caring for people with rare conditions and making sure that they have easy access to high-quality sources of information is central to effective care.

Easy access to accurate information is also important for people within the rare diseases community and we are committed to giving people the information they need to navigate and take control over their care (see below, ‘Information accreditation’).

Information accreditation 

Finding information on rare conditions can often be challenging. When patients are diagnosed with a condition, healthcare professionals do not always have enough knowledge to provide them with the information they need. In the rare diseases community, there are many patient support groups and charities creating information for patients. This includes health information as well as where to get support and meet other people with the same condition.

We recognise the important role patient support groups can play in developing reliable and easy to access information on rare conditions. Research by Ipsos published in November 2024 found trust in condition-specific patient-organisation websites is high; 8 in 10 UK adults with a long-term condition agree having access to trustworthy information would help them manage their condition.

The PIF TICK is an independently-assessed certification for health information. It allows healthcare professionals to know they can trust the information provided and confidently share it with their patients. A PIF TICK shows an organisation’s health information production process has been independently assessed against 10 key criteria:

• systems: information is created using a consistent and documented process
• training: staff receive ongoing training and support
• need: resources meet a genuine need
• evidence: information is based on reliable, up-to-date evidence which is communicated clearly
• involving users: users are involved in the development of information
• health inequalities: information is written to meet health literacy, digital inclusion, language and accessibility needs of the audience
• transparency and legal: information complies with General Data Protection Regulation (GDPR), promotion of medicines and other regulations
• feedback: there is a clear process for users to provide feedback
• disseminating: information is promoted to maximise reach
• impact: the impact of information is measured

The PIF TICK is run by the Patient Information Forum (PIF), a charitable-incorporated organisation. It operates on a not-for-profit basis. Fees cover the cost of operating the scheme and are based on the sector, income and size of the applying organisation or individual. All applicants are supported by an expert assessor and gain access to PIF’s consensus guidance on key health information production topics.

Organisations not yet ready to apply for the PIF TICK assessment can still join PIF’s vibrant, cross-sector membership of more than 300 organisations. This grants access to consensus guidance and hot topic webinars, all aligned with the PIF TICK criteria. PIF also offers summary guidance for free on its website to help improve the quality of all health information.

Over the coming year we will work with PIF TICK and patient support groups to determine the extent to which this scheme can be used by interested rare disease patient groups to facilitate the recognition of the information they produce by healthcare professionals. This is designed to supplement existing initiatives, such as the Genomic Education Programme, to produce information on rare diseases. We acknowledge that many patient organisations will not have the resources or capacity to produce such information. However, our aim is to signpost to the support available for those who do. NHS England will determine how to best promote the use of PIF TICK recognised information on rare diseases with healthcare professionals.

Better co-ordination of care

Many people living with rare conditions will need to access care through multiple specialists and continue to experience challenges with this care being poorly co-ordinated. People often find that they face logistical challenges, like needing to attend multiple hospital appointments on different days, and have to become experts on their own (or their loved one’s) condition to effectively advocate for their care. Reports such as the Coordinating Care report published by Genetic Alliance UK highlight the burden on patients and families when they have a multi-system rare disease that requires interactions with a range of specialties and health professionals.

Healthcare services for rare diseases are mainly commissioned through specialised or highly specialised services (HSS) in NHS England. We are pleased to report care co-ordination is now an embedded requirement of rare disease service specifications and a toolkit is now available on use of virtual clinics in HSS, giving people access to co-ordinated care of multiple specialists and shifting care from hospital to home. More information on existing actions is set out in section 2. In addition to continuing to make progress against existing actions, NHS England will also deliver against a new action on co-ordination of care in the year ahead.

Action 37: clinics for multi-system disorders

Having a treatment management plan that is jointly agreed across all professional groups involved in the care of a patient is more likely to result in optimal outcomes. NHS England already has a track record of commissioning specific services that include the provision of highly successful ‘carousel’ clinics, for example for DNA repair disorders. However, these can take time to put in place. This is partly because the current process by which patient contacts (such as an outpatient attendance) are recorded on an individual basis, and with the limits around recording multiple attendances on the same day, does not incentivise providers to run joint clinics.

This action seeks to address this challenge by putting in place a structural methodology that incentivises providers to run clinics for multi-system disorders, reducing the number of individual appointments and burden of co-ordination of care on families.

Care co-ordinators

Care co-ordinators help to co-ordinate and navigate care across the health and care system, helping people make the right connections, with the right teams, at the right time. Effective care co-ordination can enhance the quality of life for individuals with rare diseases. Care co-ordinators can support people to become more active in their own health and care and are skilled in assessing people’s changing needs. Care co-ordinators are effective in bringing together multidisciplinary teams to support people’s complex health and care needs, and can connect people with rare diseases to patient organisations.

The NHS England Workforce development framework for care co-ordinators provides guidance for care co-ordinators in the NHS and those employing them. It sets out professional standards and competencies, and gives guidance on supervision, training and continuous professional development. The NHS Genomics Education Programme is designed for all healthcare professionals, and includes information on rare diseases for non-specialists through ‘bitesize’ genomics content.

The NIHR-funded CONCORD study of care co-ordination found that only 12% of patients and 14% of parents or carers of those affected by a rare disease have access to a formal care co-ordinator. The study also found that different people had different preferences for how they wanted their care to be co-ordinated. The second phase of this study is exploring economic models to optimise care co-ordination within the NHS, with further detail reported under action 20 in section 2.

Improved access to specialist care, treatment and drugs

The development of improved therapies and care remains of key importance for people living with rare conditions. There is enormous unmet need and currently only around 5% of rare diseases have an effective treatment. The UK has a strong life sciences sector and there are multiple initiatives in place to support research and to pull through cost-effective therapies into the NHS. In some cases it is possible to use existing medicines in new ways to treat rare diseases, as described below in ‘Using existing medicines in a new way to treat rare diseases - navigating a path to patient access’. In other cases, new therapies need to be developed, with safety being at the heart of innovation. To support this, we have committed to new actions this year reforming regulation of clinical trials, and developing an operational framework for individualised medicines for ultra rare diseases.

Using existing medicines in a new way to treat rare diseases - navigating a path to patient access

To provide appropriate treatment options for rare conditions, it is sometimes possible to use existing medicines in new ways, outside of their current marketing authorisation (or ‘licence’). This is sometimes known as ‘medicines repurposing’ and is a complementary approach to pharmaceutical companies developing brand new treatments. There is significant interest in the potential for using existing medicines in new ways among many people living with rare conditions and those who care for them, given the huge unmet need and challenges with developing medicines for rare conditions.

Clinicians are very familiar with the option of prescribing medicines outside their licence (known as ‘off-label’ use). For medicines used by specialists to treat a rare disease, off-label access is often agreed at a local level, informed by the available evidence and where the clinician feels this best meets the needs of the patient. When needed, 2 further routes can support routine patient access to a repurposed medicine in England: developing a national clinical commissioning policy for the medicine (for nationally commissioned services only), and/or securing a licence variation via the repurposing programme. These routes require supporting research evidence, as outlined below.

For specialised services commissioned and funded by NHS England (as is the case for many rare disease treatments), a clinician can propose a new or revised national clinical commissioning policy where they feel there is sufficient supporting evidence. The process is explained in this video:

The NHS England specialised commissioning preliminary policy proposition (PPP).

NHS England develops clinical commissioning policies in line with published methods and eligibility criteria. A clinical commissioning policy can recommend medicines that are used off-label or on-label.

The Medicines Repurposing Programme was established in 2021 and can support medicines for both rare and non-rare conditions. It focuses on medicines where a licence variation is likely to be a critical factor in enabling patient access (a licence variation means adding a new use of a medicine to the marketing authorisation, bringing it ‘on-label’). Securing a licence variation is likely not required if there is existing off-label prescribing practice, or if a national policy supporting off-label access can be developed.

The Medicines Repurposing Programme offers tailored support to medicines that meet the programme eligibility and prioritisation criteria. The support might include facilitating further research and/or help to apply for a licence variation. The repurposing programme communicates and co-ordinates across agencies, but it does not issue treatment guidance, regulate medicines, make commissioning decisions or set the price of medicines. These functions remain the responsibility of the relevant arm’s length body (ALB) or department.

As the Medicines Repurposing Programme focuses on medicines that require a licence variation, most medicines in the programme are for non-rare conditions where prescribing is by non-specialists. As reported in the 2024 England Rare Diseases Action Plan, the Medicines Repurposing Programme is supporting a potential treatment for a rare condition: tuberous sclerosis complex. The NIHR Efficacy and Mechanism Evaluation Programme has now agreed to fund a trial to find out if the diabetes medicine metformin reduces the number of seizures in people with tuberous sclerosis complex.

There are clinical evidence requirements for both developing a national clinical commissioning policy for a medicine and for the repurposing programme. To propose a clinical commissioning policy, original peer-reviewed evidence published within the last 10 years is required. The Medicines Repurposing Programme requires evidence of safety and efficacy in the repurposed use, such as a completed phase 2 trial (although the programme takes into account that high-quality research may be more challenging for rare conditions).

Support is available to charities, academics or clinicians who wish to generate further research and clinical evidence on the safety and efficacy of a new use of an existing medicine. Between the MRC schemes and NIHR research programmes, the funding pathway encompasses:

• pre-clinical refinement, safety and early clinical trials - MRC Developmental Pathway Funding Scheme (DPFS)
• definitive efficacy trials, which may also explore the mechanism of action - MRC-NIHR Efficacy and Mechanism Evaluation (EME) programme
• definitive effectiveness studies, which compare an intervention against current practice - NIHR Health Technology Assessment (HTA) programme

The NIHR Research Support Service (RSS) helps researchers navigate the funding landscape and supports the development of applications to these and other national peer-reviewed research programmes.

NIHR has also begun a review of the repurposing landscape, with a particular focus on rare disease research. This will look at the applications and projects in the MRC and NIHR portfolios to better understand the level of activity, and will identify any challenges, gaps or barriers in the funding pathway. In its later stages in 2025, the review will invite feedback from stakeholders on an options appraisal of activities to address any areas identified.

Action 38: reform of the clinical trials regulations

The Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024, laid in Parliament on 12 December 2024, will be subject to debate before being made into law. Once enacted, it will come into force following a 12-month implementation period. This legislation reflects the MHRA’s commitment to reforming clinical trials regulations, following an extensive consultation conducted in 2023.

Clinical trials for rare diseases face specific challenges where there are low numbers of individuals with a given condition, such as in patient recruitment, trial design and regulatory frameworks. The implemented changes to clinical trial regulations aim to address some of these challenges, including:

• ensuring patients and their safety are at the focus of all clinical trials and bring the benefits of clinical trials to everyone
• creating a proportionate and flexible regulatory environment
• cementing the UK as a destination for international trials
• providing a framework that is streamlined, agile and responsive to innovation

The proposed updates to the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 includes specific reference to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines for good clinical practice (GCP) principles - more simply known as ICH GCP - instead of a set of UK specific expectations, ensuring alignment with internationally accepted standards for clinical trial design, conduct, safety and reporting. This alignment will facilitate the mutual acceptance of UK-generated clinical trial data by global regulators, supporting the UK’s role in multi-regional clinical trials.

While compliance with the full ICH GCP guidance is not required for all trials, only those applying for a marketing authorisation, it is anticipated that the adoption of the ICH GCP principles into UK law will enhance interoperability and acceptance of the outcomes of academic trials while supporting pragmatic and risk-based approaches. The MHRA is an active member of ICH and has been fully engaged with the revision of the ICH GCP guidance to ensure its acceptability in the UK and ensuring that it reflects the use of modern and proportionate ways of working.

The new clinical trials regulations will mandate the notification route for some clinical trial (initial and amendment) submissions according to specific criteria. Introducing this approach will safely accelerate the approval of these trials.

The implementation of a lapse period for approvals of clinical trials in which no participants have been recruited is included. In response to stakeholder feedback received during the consultation, provisions have been incorporated in the legislation for deferrals or extensions to the lapse period, supported by a clearly defined process for submission, review and approval of such requests. This will help give flexibility to clinical trials in rare diseases where recruitment of participants, for example people with specific variants, is complex.

The legislation does not restrict the ability of trial sponsors accessing requests for further information (RFI) as they are finalised by each review discipline, rather than waiting for all disciplines to complete their assessments. This will be made possible in the future via updates in the IT infrastructure. This approach, which received strong support during consultation, aims to streamline the process while maintaining clarity that RFIs will not be released piecemeal or with staggered response times. The response clock will begin only once all disciplines have completed their reviews, ensuring sponsors have a consolidated timeline to respond. This change is particularly expected to benefit the rare disease community by accelerating trial processes and addressing urgent needs, with additional advantages noted for phase 1 trials where time-sensitive schedules are common.

In response to consultation feedback, the MHRA will develop detailed guidance on patient and public involvement in clinical trials, emphasising best practices rather than introducing legislative requirements. This approach ensures flexibility, recognising that appropriate involvement varies depending on the stage or type of trial. The guidance will provide clear definitions and expectations while avoiding legal burdens, supporting the overarching goal of enhancing the UK’s appeal as a destination for innovative clinical research. It will underline the value of involving individuals with relevant experience, such as patients, family members or carers, to improve research quality and relevance. Proportionate involvement will be encouraged, considering the specifics of each trial, with recognition of patient engagement activities conducted outside the UK in multinational studies, where appropriate.

Ongoing collaborative efforts between regulators, funders and research teams to promote patient and public involvement will be supported and enhanced through this guidance. The aim is to ensure meaningful engagement, avoid a one-size-fits-all approach and align with the broader goal of increasing trial activity in the UK while benefiting patients through innovative research.

The legislation has also been amended to allow regulators to take targeted actions, such as suspension or termination, against specific parts of a clinical trial, rather than only addressing the trial as a whole, while retaining the existing powers to amend, suspend or terminate an entire trial. This approach, particularly relevant for advanced therapy medicinal products (ATMPs) and novel trial designs, will enable regulators to address safety or compliance issues within specific trial components without disrupting unaffected parts.

As part of the legislative process, the equality impact assessment has been informed by the detailed evidence provided. The new regulations streamline the process of running clinical trials, making it more efficient and encouraging a greater number of trials across a wider range of medicines in the UK. This approach will help bring the benefits of innovative medicines to patients throughout the UK. By maintaining an attractive environment for multi-country trials, we aim to facilitate research into rare diseases, where low incidence rates often necessitate recruitment from multiple countries. These measures will ensure that the UK remains a competitive and inclusive hub for cutting-edge clinical research.

Advanced therapies for rare diseases

The UK is a global leader in the development of advanced therapies, with a strong academic and life science industry, and was the first national health system in Europe to commission CAR-T cellular therapy for blood cancer patients.

In our first England Rare Diseases Action Plan, NHS England committed to developing a strategic approach to commissioning ATMPs. This has involved building horizon scanning capabilities and working with pharmaceutical companies to anticipate future demand. ATMPs are treatments for human use that are based on genes, tissue or cells. These therapies target the underlying causes of disease, rather than treating symptoms. Advanced therapies offer the potential to provide significant, long-term benefits for certain patients with debilitating or life-shortening diseases and potential for enormous growth in the life sciences sector.

There are currently 13 ATMPs in use in the NHS across 15 indications for rare diseases and cancer. Thirty hospitals in England are delivering ATMPs, with over 1,700 patients completing ATMP treatment to date. The number of ATMPs coming to market is set to increase substantially. Based on NHS horizon scanning a further 20 ATMPs are anticipated to launch in 24 indications by the end of 2026, although it should be noted that attrition and delays to launch for ATMPs are common. The reasons for this are varied and can relate to the clinical development, regulatory, HTA, commercial and manufacturing processes.

Recognising the transformative potential of ATMPs and the opportunities and challenges from the expected increase in numbers of these therapies becoming available, in September 2024 DHSC stood up an advanced therapies co-ordination group spanning public sector partners. This group aims to create a joined-up ecosystem that will support the development, regulation and delivery of all ATMPs, including those for rare diseases in the UK. Patient voice is represented within the group by a co-chair of the multi-stakeholder patient group ATMP Engage. Industry voice is brought in through connecting with existing groups such as the Cell and Gene Collective, the Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA). Currently subgroups are examining what steps are needed to ensure that the data infrastructure and workforce are fit for the future needs.

We continue to invest in ATMPs through initiatives such as the Cell and Gene Therapy Catapult. With £17.9 million of new funding via NIHR, the Advanced Therapy Treatment Centres will be driving forward work to enhance the UK environment for ATMP clinical trials and progress research within the NHS to ensure patients can get safe access to these innovative therapies.

In addition, the Innovation Hubs for Gene Therapies (funded by LifeArc, MRC and the Biotechnology and Biological Sciences Research Council (BBSRC) provide clinical grade viral vector manufacturing capability for academic researchers, alongside translational and regulatory support, to accelerate the development of novel gene therapies. The Innovation Hubs offer a range of services, including:

• viral vector manufacturing
• research and development
• process development
• quality assurance
• plasmid manufacturing

To-date, brand new facilities have been built and validated, significant work has taken place to establish efficient manufacturing platforms and the innovation hubs are now working with several academic groups. The innovation hubs are working towards self-sustainability and are currently developing their future strategy.

Individualised therapies 

Advances in genomics mean that we can now sequence the whole genome of people with a suspected rare disease. For many people with a condition caused by a variation in their DNA, we can now pinpoint the part of their genome causing the disease. Advances in technology also mean that it is now possible, in some cases, to develop highly personalised therapies specific to this DNA variation to address the root cause of the condition. This can include using cutting edge techniques such as gene editing (for example, CRISPR), antisense oligonucleotides (sometimes referred to as ASOs) or mRNA therapies.

For some rare conditions this raises a life-changing or life-saving opportunity to generate personalised or even individualised therapies for those who have a unique variant in their DNA, or are one of only a handful of people living with a condition. Therapies to treat such rare conditions are often referred to as a group as individualised therapies or n-of-1 therapies, irrespective of the technology underpinning the treatment. These therapies are new and will pose challenges for regulation, reimbursement and service delivery. For example, it is not possible to run standard clinical trials when a therapy is specifically designed for an individual or a very small number of individuals (as discussed in an article published by Nature Reviews Drug Discovery).

Recognising the potential of these technologies, this government is making significant investments in research to support their development. This includes through the UK Platform for Nucleic Acid Therapy for rare disease treatment (UPNAT) (see below), funded by MRC and NIHR as part of the £14 million Rare Disease Research UK platform. The Nucleic Acid Therapy Accelerator (NATA), funded through the MRC, operates at the intersection of academia, preclinical research and industry to advance the development of nucleic acid therapies and associated technologies.

In December 2024, the MRC launched the first 2 MRC centres of research excellence (CoRE), both studying gene therapies, and each worth up to £50 million over 14 years. The MRC CoRE in therapeutic genomics aims to achieve transformative impact for rare genetic disorders and will develop processes to take successful genetic therapies and re-programme them to treat new disorders, enabling the development of individualised therapies at scale.

This investment in research, combined with the UK’s capabilities in diagnostic genomics (which enables the identification of people who could benefit from these therapies), a single payer healthcare system and responsive and flexible regulator, gives the UK the opportunity to play a world-leading role in treating rare disease with advanced therapeutics. This will bring benefits for both patients and the UK life sciences sector. Alongside UPNAT, the Rare Therapies Launch Pad (see below) will be key to developing thinking and testing pathways around a risk-proportionate regulatory system, patient and genetic variant identification, ethics and consent, data requirements and reimbursement for antisense oligonucleotides as a pilot that can be built on for wider individualised therapies.

UK Platform for Nucleic Acid Therapy for rare disease treatment (UPNAT)

UPNAT is working to address challenges in individualised therapies based on nucleic acid therapy (NAT), including:

• a lack of a national network for knowledge and expertise sharing between centres leading NAT preclinical and clinical development
• a clear path for systematically linking patients who have unique variants to NAT expertise
• the need for continuous dialogue between regulators and researchers to streamline the process of regulatory approvals
• accelerating the clinical translation of rare disease specific NATs

As part of this work, it will generate underpinning resources which can be built on by regulators and NHS England to support safe and effective delivery of these therapies to patients. This will include generating target and patient selection guidelines for NATs in the UK. Workshops to develop these guidelines will be held later this year and a preprint of the guidelines is expected to be available towards the end of the year.

UPNAT will also work to promote communications, public engagement and raise awareness of experimental NAT development among rare disease patients, families, charities, advocacy groups and clinical centres. The aim is to make sure that these groups are engaged and well informed about the potential and the risks of experimental nucleic acid therapies. This work will result in a patient-family handbook on NAT therapy developed with input from charities. The draft handbook will be made available for feedback early in 2026.

The platform will also develop a guidance document on preclinical development considerations for NAT products, aiming to support their progression through the product lifecycle. This document is expected to be ready for publication in 2026.

Rare Therapies Launch Pad

The Rare Therapies Launch Pad (RTLP) aims to develop an end-to-end pathway for patients with rare, life-limiting genetic conditions to access individualised therapies. Initially, the RTLP will focus on a pilot project that explores the use of individualised antisense oligonucleotide (ASO) treatments for children with rare and life-threatening neurological conditions.

‘n-of-1’ ASOs are individualised therapies that target ribonucleic acid (RNA) in a very specific way to halt or slow down the progression of diseases caused by a genetic variant. They potentially provide an opportunity to treat individuals with genetic conditions for whom there is currently no available therapy. The pilot plans to enrol a small number of patients over a period of 3 to 5 years, generating vital evidence to identify the elements and infrastructure of a sustainable and scalable regulatory and reimbursement approach, to enable the delivery of individualised therapies in the future across a broader range of rare conditions and treatment modalities.

The RTLP is a consortium of members with a governance structure that includes a board of directors, a programme lead and a steering committee. Day-to-day operations and deliverables are undertaken by 4 working groups, drawing on the diverse expertise in the consortium. These currently include the Patient and Clinical Pathway, Regulatory, Reimbursement, and Communication and Engagement working groups.

The RTLP continues to engage with DHSC, Genomics England, University of Oxford, Oxford-Harrington Rare Disease Centre, ABPI, Mila’s Miracle Foundation, Great Ormond Street Hospital, UCL, UK Platform for Nucleic Acid Therapies (UPNAT), Birmingham Women’s and Children’s Hospital, EveryONE Medicines, Yu Lab at Harvard Medical School, MHRA, NICE, NHS and others in the rare disease space both in the UK and abroad, who are supporting its objective to develop proposals. The intention is to formalise the RTLP as a community interest company (CIC) supported by funding and donations from other not-for-profit organisations and commercial entities.

In December 2024, Genomics England hosted a workshop with representatives from DHSC, the Office for Life Sciences (OLS), MHRA, NICE and NHS England, with presentations from experts from the field and people with lived experience of rare conditions. A summary of this workshop is included in annex B. This further supported thinking about the future of these therapies and how to improve the UK’s preparedness to harness the opportunities that they could bring for UK patients and also for the UK life sciences sector. In autumn 2025, DHSC will reconvene this group to discuss progress. In parallel, OLS and the Cell and Gene Therapy Catapult will hold a workshop with the life sciences sector to provide an update and draw in perspectives.

The Commission on Human Medicines provides advice to ministers and the MHRA on the safety, efficacy and quality of medicinal products. The scope of its Highly Personalised Medicines Expert Working Group (HPMEWG) has been extended to include providing advice on regulation for individualised genetic therapies for rare disease, and will include engaging in discussions with representatives from initiatives such as the RTLP in the year ahead.

The NICE HTA Lab enables NICE to develop creative solutions to complex problems in health technology assessment (HTA). One project is exploring the value assessment of personalised therapies by identifying potential issues relating to the clinical and cost effectiveness evidence for these technologies. The project will give specific consideration to individualised therapies, including whether their evaluation would fall under the remit of NICE and whether it will require a tailored approach.

Action 39: developing an operational framework for individualised therapies in the NHS

NHS England recognises the opportunities for individualised therapies in providing life-changing treatments for certain rare disease patients but also the challenges these therapies could pose for service delivery. Some of these therapies are being produced by not-for-profit organisations who are able to offer the therapy free of charge and it may be the case that we have individuals in the UK with that same very specific genetic variant who could benefit.

Over the coming year, NHS England will explore the development of a highly specialised service operational framework for service delivery of individualised or n-of-1 therapies to patients within the NHS, detailing what needs to be in place when commissioning a service. This will initially focus on ASOs, but could be built on for other individualised therapies. This will include specifying what constitutes an optimal and safe service model and how to select service providers. It will build on experiences in other countries. As with other innovative treatments, the framework will need to take account of the value and affordability of the therapies.

Building on work by UPNAT and the RTLP, MHRA and NICE, the framework will need to align with criteria for identifying which patients would be eligible for treatment. NHS England will also engage with partners, including MHRA and NICE, to seek clarity around pathways for regulation and evaluation of these therapies. Such pathways would need bespoke processes for regulation, evidence gathering, reimbursement and patient identification, striking a balance between aligning with other arrangements for medicines but clearly recognising the difference in terms of the numbers of eligible patients.

The planned output will be a national operating framework for how NHS-commissioned n-of-1 therapies will be delivered to patients, which may include bespoke models for specific technologies (for example, ASOs). The scope of the framework will be agreed by February 2026 and reported in the England Rare Diseases Action Plan. In the long term, outcomes will be the safe and affordable provision of individualised therapies to eligible patients within the NHS.

Section 2: progress report on actions in England’s 2024 Rare Diseases Action Plan 

This next section of the action plan reports on progress made against open actions from England’s rare diseases action plans. Over the first 4 years of the UK Rare Diseases Framework we have introduced a total of 39 actions. The table below lists these actions. The summary below groups actions according to the 4 priorities and cross-cutting themes of the framework. Further detail is provided in annex A.

Over the last year the progress of ongoing actions from our 3 previous action plans has continued to be monitored through our England Rare Diseases Framework Delivery Group. The group brings together publicly funded delivery partners and representatives of the rare disease patient and clinician communities, and meets regularly to review delivery of existing commitments and agree on future activities. In addition to our regular meetings, in September 2024 we held an in-person all day meeting of this group where progress was presented and future collaboration discussed. Progress has also been reported and discussed at the UK Rare Diseases Framework Board and at the UK Rare Diseases Forum, with feedback returned to the delivery group.

Table 1: summary of actions from England’s rare diseases action plans

Action	Year of Rare Diseases Action Plan	Priority and status	Owner(s)
1: improving how decisions are made on newborn screening	2022	1 - ongoing	DHSC
2: WGS to screen for genetic conditions in healthy newborns study	2022	1 - extended	Genomics England, NHS England
3: continuously develop the National Genomic Test Directory	2022	1 - concluded (2023)	NHS England
4: further develop the Genomics England clinical research interface	2022	1 - concluded (2023)	Genomics England
5: pilot new approaches for patients with undiagnosed rare conditions	2022	1 - extended	NHS England
6: develop an innovative digital educational resource (‘GeNotes’)	2022	2 - extended	NHS England (National Genomics Education Programme)
7: how best to include rare diseases in UK health education and training	2022	2 - extended	NHS England (National Genomics Education Programme)
8: extend remit of the Genomics Education Programme (GEP)	2022	2 - extended	NHS England (National Genomics Education Programme)
9: publish high-quality epidemiological and research papers	2022	2 - concluded (2023)	NHS England
10: develop a toolkit for virtual consultations	2022​	3​ - concluded (2024)​	NHS England​
11: support rapid access to drugs for patients with rare diseases ​	2022​	4​ - concluded (2024)​	NHS England​
12: develop a strategic approach for gene therapies and other ATMPs ​	2022​	4​ - concluded (2025)​	NHS England​
13: capitalise on the changes made to NICE’s methods and processes ​	2022​	4​ - ongoing	NICE​
14: monitor overall uptake of drugs and map geographical access​	2022​	4​ - ongoing	NHS England (HSS and the National Disease Registration Service (NDRS))​
15: map the rare disease research landscape to identify gaps and priorities	2022​	4​ - concluded (2025)​	DHSC and Medical Research Council (MRC)​
16: reduce health inequalities in NHS HSS ​	2022​	4​ - concluded (2023)​	NHS England ​
17: commission research on how best to measure the diagnostic odyssey​	2023​	1​ - extended​	DHSC​
18: increased data-sharing for patient benefit ​	2023​	1​ - extended​	Genomics England, NHS England (NDRS)​
19: strategies for increasing awareness of rare diseases in the health workforce​	2023​	2​ - extended​	NHS England (National Genomics Education)​
20: commission research to operationalise better co-ordination of care ​	2023​	3​ - extended​	DHSC​
21: include definition of co-ordination of care in services specifications for patients with rare diseases​	2023​	3​ - extended​	NHS England​
22: improved ‘findability’ of people living with rare diseases using NCARDRS​	2023​	4​ - ongoing	NHS England (NDRS)​
23: improve understanding of the impact of NHS England’s specialised services commissioning activities on rare disease patients ​	2023​	4​ - concluded (2024)​	NHS England​
24: establish a HSS programme board and strengthen role of NHS England in commissioning wider services ​	2023​	4​ - concluded (2024)​	NHS England​
25: review effectiveness of EAMS, ILAP and the IMF in supporting access to treatments ​	2023​	4​ - extended​	NHS England, NICE, MHRA​
26: registration of national data for exemplar rare genetic conditions which cause an inherited predisposition to cancer​	2023​	4​ - ongoing	NHS England​
27: improving the Be Part of Research platform ​	2023​	4​ - ongoing	DHSC, NIHR​
28: develop a plan to include rare diseases in NHS England’s Core20PLUS5 Framework​	2023​	4​ - ongoing	DHSC, NHS England​
29: commission portfolio level evaluation of England’s rare diseases action plans	2023​	4​ - extended​	DHSC, NHS England​
30: develop a genomics communication skills resource​	2024​	2​ - extended	NHS England (National Genomics Education)​
31: develop specialist genomics workforce through the GTAC​	2024​	2​ - extended	NHS England (National Genomics Education)​
32: implement networked models of care ​	2024​	3​ - ongoing	NHS England​
33: develop a funding mechanism that incentivises centres to undertake whole body scans	2024​	4​ - extended	NHS England (HSS and NDRS)​
34: review effectiveness of IDAP pilot in supporting access to medical devices ​	2024​	4​ - closed (2025)	MHRA​
35: publish and disseminate a health inequalities toolkit, for HSS​	2024​	4​ - ongoing	NHS England​
36: map and measure the geographic spread of patients accessing HSS​	2024​	4​ - extended	NHS England​
37: clinics for multi-system disorders​	2025​	3 - ongoing	NHS England
38: reform of the clinical trials regulations	2025​	4​ - ongoing	MHRA​
39: develop an operational framework for individualised therapies in the NHS	2025​	4 - ongoing	NHS England​

Priority 1: helping patients get a final diagnosis faster 

The UK Rare Diseases Framework highlighted the importance of getting a rapid and accurate diagnosis. This can:

• ensure timely access to treatment and care
• provide a possible prognosis
• offer options for family planning

The diagnostic odyssey - the often lengthy delay between symptoms first presenting and receiving a diagnosis - can represent years of anxiety, financial difficulties, impacted career and educational opportunities, and deterioration of physical and mental health. We have commissioned research to better understand what causes the diagnostic odyssey so we can improve it (action 17). This work is underway, with Consilium Scientific and Realise Advocacy in the process of identifying 150 ‘indicator’ conditions.

Around 80% of rare conditions have a genetic basis, and in England genomically informed care and treatment is provided by the NHS Genomic Medicines Service. As more conditions can now be tested for in the GMS due to our understanding developing, we acknowledge that turnaround times have been impacted. Minimising backlogs and the time taken to deliver a genomic test is a key priority for NHS England and the NHS Genomic Laboratory Hubs (GLHs), for example through Maximising the Patient Benefit of Genomics – the evolving role of the Clinical Genetics Services to make sure resource is used in the most impactful way.

The UK National Screening Committee’s (NSC) Blood Spot Task Group (BSTG) continues work to identify approaches to help researchers develop evidence that can support the UK NSC to make good recommendations for whether conditions should be added to routine newborn screening (action 1). The NSC routinely considers international evidence. Progress has been made on in-service evaluations (ISEs) for severe combined immune deficiency (SCID) and spinal muscular atrophy (SMA). In addition, a new evidence review into newborn screening for metachromatic leukodystrophy will take place during 2025 to 2026.

Beyond routine screening, the Generation Study is now underway as an NHS embedded research study that aims to undertake WGS on up to 100,000 babies, and screen for over 200 rare conditions (action 2). Currently, the study is open and recruiting at 27 hospitals across 18 NHS trusts. Any results have started to be returned to participants.

We continue to look at new approaches for people who do not have a diagnosis for their rare condition (action 5). Building on the learnings from pilots in Wales, we are working to set up 2 clinics for SWAN pilot clinics within the NHS in England. The service description and provider selection plan has been agreed. However, further progress is dependent on new funding, and we anticipate we will need to pause before commissioning the 2 pilot sites in the 2026 to 2027 financial year. We remain committed to taking these pilots forward to demonstrate how care for patients with undiagnosed conditions can be improved. Pioneering research and development of platforms like DECIPHER also continues to build our understanding of rare diseases and help more people get a diagnosis, as highlighted below.

Case study: DECIPHER

DECIPHER is a free web platform for safely sharing genomic variant data linked to clinical features (phenotypes) from rare disease patients with impressive capabilities. DECIPHER is funded through the Wellcome Trust. Its dynamic interfaces enable understanding of genomic and phenotypic data to power more informed and up-to-date variant classification and clinical interpretation. Patient phenotypes are captured alongside quantitative data, which is combined to derive gene‐specific summaries of clinical features. DECIPHER currently holds data from 325 contributing centres in 45 countries, openly sharing 50,000 anonymous patient records. DECIPHER also supports controlled sharing of data between trusted partners, for example a consortium in DECIPHER which links all NHS genetic services in the UK.

DECIPHER helps drive rare disease research and clinical diagnosis. Diagnosing rare diseases is difficult, as an individual clinician may only ever see one patient with a particular ultra rare disease. DECIPHER enables the matching of patients with similar disorders and contact between their clinicians. Since its inception in 2004, DECIPHER has made a huge impact on rare genetic disease research and has been cited in more than 4,000 publications.

Included in DECIPHER are results of the Deciphering Developmental Disorders (DDD) study - a UK-wide initiative that recruited and analysed data from around 13,500 patients affected with developmental disorders (and their parents). Collaboration with the patient support group Unique led to the development of leaflets for many of the newly discovered disorders, which include essential guidance for families affected by these disorders. Such partnerships are crucial for including patient voices in research.

This year marks a decade since the launch of the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS), part of the National Disease Registration Service (NDRS) now hosted by NHS England. Established in 2015, NCARDRS has become a cornerstone of the UK’s commitment to using data to improve the lives of people affected by congenital anomalies and rare diseases. National disease registries capture a patient’s complete journey from referral, diagnosis, treatment, outcomes, experience and survival through the collection, curation and linkage of many differing data sources into a unified information resource. Many patients with rare diseases receive a diagnosis through genomic testing, and increased safe data sharing between Genomics England and the NHS will bring patient benefit by increasing the number of rare disease patients whose data was registered within NCARDRS as part of a well characterised cohort (action 18).

Priority 2: increasing awareness of rare diseases among healthcare professionals

People with rare diseases often interact with many different healthcare professionals over their health journey. This includes primary care staff such as GPs, emergency care staff and specialists. With over 7,000 rare diseases, no healthcare professional can receive training on every rare disease. By raising awareness of rare diseases more broadly, healthcare professionals can be alert to considering them, for example at first presentation or in emergency settings, and confident about where to go to for additional support and resources.

Rare Disease Day 2024 was the first time activities were co-ordinated across the NHS. Each trust was empowered to deliver their own activities and communication on the day through a toolkit shared from the central communications team. As well as centrally led efforts from NHS England, organisations such as Medics4RareDisease (M4RD) and Genetic Alliance UK played a significant role in raising awareness of healthcare professionals on Rare Disease Day 2024. We have worked to build on this to further extend activities for Rare Disease Day 2025.

NHS England’s flagship GeNotes resource continues to grow, with more than 500 resources featured across 9 specialties (action 6). GeNotes includes resources on ‘non-genetic’ rare diseases, and work continues, in partnership with M4RD, to expand the programme’s coverage (action 8). GeNotes attracts visitors from both within the UK and beyond and has been accessed by 370,000 individuals worldwide to date. Of these, this year over 117,000 visitors accessed the page from the UK, with nearly 270,000 total page views. NHS England has been working with M4RD to improving the awareness of GeNotes and wider resources with healthcare professionals.

In addition, the National Genomics Education Programme is also developing a range of training and educational resources on rare diseases to include rare diseases in UK health professional education and training frameworks (action 7). NHS England is working collaboratively with the Academy of Medical Royal Colleges (AoMRC) Genomics Professional Partnership Group (GPPG) on the evaluation of medical curricula and development of training frameworks, to ensure information on rare disease is appropriately integrated.

Raising awareness is important across all healthcare professionals, and the Genomics Education Programme has undertaken specific work to develop resources for the nursing and midwifery, pharmacy and primary care workforce (action 19). NHS England has also been developing a communication skills resource to aid healthcare professionals in having sensitive conversations, including trialling a virtual reality solution, to ensure the patient feels supported in their diagnosis of a rare condition (action 30).

For the specialist genomics workforce, the Genomics Training Academy (GTAC) is a national initiative led by NHS England’s Genomics Education Programme and Genomics Unit (action 31). The academy provides training and education to the specialist genomics laboratory and clinical workforce within the UK. In September 2024 a number of virtual reality learning packages were launched showing laboratory orientation and processes in an immersive environment. This will be available across Genomic Laboratory Hubs for trainees.

​Priority 3: better co-ordination of care 

Rare diseases are often life-long conditions, affect different parts of a person’s body and have impacts on different aspects of their health and lives. People living with rare conditions need support from many different parts of the health and social care system, as well as from wider services, throughout their life. Ensuring that different aspects of care are co-ordinated is important to improving health outcomes, reducing financial burdens on families, and reducing health inequalities. We have commissioned research to build on the CONCORD study with RAND Europe and University of Cambridge. Work is now underway to understand how to best make improvements to care co-ordination in a way which aligns to the needs of patients with rare conditions and which is as cost-effective as possible for the NHS (action 20). Findings will be reported in 2026.

Action 21 set out to include the definition of co-ordination of care as defined in the CONCORD study in all new and revised services specifications within the NHS for patients with rare diseases. Following this change, service specifications for 2 conditions are being published which include the definition of co-ordination of care: cystinosis and haemophilia (which will be published later this year). This number will increase as service specifications are produced or renewed over time.

Hospital to home

Patients with rare disease experience a burden of care that is often exacerbated by the need to access specialist care that is far away from home. While it is important that expertise is co-located around centres of excellence, this can make it challenging for people to access the care they need when they need to travel.

NHS England has published a toolkit for virtual consultations (action 10) which is improving the use of videoconference and telephone clinic calls in services for patients with complex, multi-system rare diseases. The toolkit provides acute hospital teams with guidance when setting up or improving the safety and efficiency of already established, virtual and phone clinics. It was contributed to by multidisciplinary clinician team members from NHS England HSS.

During this year NHS England has made good progress towards putting in place the framework needed to commission amyloidosis and inherited metabolic disorders networked models of care. These networked models of care will ensure patients can access specialist care as close to home as possible by ensuring that specialist expertise is always available (action 32). A provider selection exercise is being run to secure amyloidosis network partners in the North West, South West, Midlands and North East and Yorkshire. These are expected to be mobilised by May 2025. A specification has been drafted for a networked model of care for metabolic services and engagement is taking place. This is dependent on funding and it is currently expected this will move forward for commissioning in 2026.  

Rare disease collaborative networks (RDCNs)

As reported in last year’s action plan, NHS England has continued to work with the NHS England Rare Diseases Advisory Group (RDAG) to review applications for new rare disease collaborative networks (RDCNs). RDCNs are an important part of NHS England’s provision to improve care and better co-ordinate care, and to support patients with rare diseases. They are made up of groups of providers who have an interest in developing understanding of a particular rare disease and are based around the principle that knowledge moves, rather than the patient, and the need to demonstrate a positive impact on patient experience and provide good geographical coverage. There are currently 25 RDCNs working across different rare conditions. These include for example the Adult Rare Bone Disease Network, covering over 450 bone disorders, and the Paroxysmal Motor Disorders Network, rare neurological diseases that affect the ability to move.

Priority 4: improved access to specialist care, treatment and drugs 

There are over 7,000 identified rare diseases, which can be both life-limiting and life-threatening, and disproportionately affect children. 75% of rare diseases affect children and more than 30% of children with a rare disease die before their fifth birthday. However, only 5% of rare conditions have an effective and approved treatment.

Improving access to specialist care, treatment and drugs is vital to save and improve lives. The UK’s strong life sciences sector and single payer healthcare system makes it well placed to be a world leader in advancing treatments for rare conditions. However, we know that new treatments in rare diseases face specific challenges around the numbers of people eligible for clinical trials, manufacturing and scale up capacity, and the regulatory environment.

In 2022, NICE implemented its updated methods and processes following extensive stakeholder engagement, giving particular consideration to the suitability of its methods and processes for treatments of rare diseases (action 13). Of note, the severity modifier was introduced by NICE in order to place greater value on health benefits provided for people with more severe diseases. A review of how the current NICE methods are working with respect to the severity modifier was presented to the NICE board meeting in September 2024. NICE will do further work to try to understand the impact this has had on rare diseases.

As part of the manual underpinning the way NICE prioritises topics, it has set out 3 key strategic principles upon which it consulted earlier this year relating to rare diseases. These principles inform decision making by NICE’s prioritisation board, which makes decisions on priorities for NICE guidance and routes medicines to the appropriate programme. The review for determining criteria for whether a medicine should be routed to NICE’s highly specialised technology programme for the evaluation of very rare diseases is currently being undertaken. The refined highly specialised technologies (HST) criteria are expected to be implemented from April 2025.

NHS England has analysed the uptake and geographical equity of drugs which had found that, in the majority of cases, overall uptake exceeded or was in line with anticipated uptake (action 14). This year, NCARDRS will explore the development of a reproducible analytical pipeline that can evaluate uptake of drugs at an individual patient level and be applied and/or scaled to other conditions or drugs.

NCARDRS is also working on improving the ‘findability’ of people living with rare diseases (action 22). NCARDRS has produced a formal rare disease data set, with input from clinical experts and aligned closely with the EU-RD Platform’s common data elements for rare disease registration. NCARDRS’ rare disease data set, including a data submission template for providers, can be found on the NDRS website.

Improving the underpinning data is important for improving access to specialist care, treatment and drugs. NCARDRS published its first Rare Disease Prevalence report on Rare Disease Day 2024. Feedback on the prevalence report will be gathered including through engagement with Genetic Alliance UK and other patient organisations. The prevalence report will be updated annually and new conditions will continue to be added in an iterative manner. NCARDRS is continuing to find a solution that allows rare disease patients to self-report for registration purposes. The interim solution of an email-based self-reporting system has been paused due to capacity constraints and limited utility of the data collected in this way. However, NCARDRS continues to explore options within the NHS England Transformation Directorate.

Some rare conditions such as neurofibromatosis type 1 and multiple endocrine neoplasia type 2 (MEN-2) result in people being more likely to develop cancer. In last year’s action plan we committed to developing a funding mechanism that sufficiently incentivises centres to undertake whole body scans for individuals with rare genetic conditions that predispose them to developing cancer prematurely (action 33). NHS England has produced a Gateway 3 paper setting out the proposed processes for identifying adult and paediatric providers, which was agreed in August 2024. Awarding of contracts will be subject to funding agreements for 2025.

NCARDRS is also improving the registration of national data for exemplar rare genetic conditions which cause an inherited predisposition to cancer, creating a National Inherited Cancer Predisposition Registry (NICPR) (action 26) from all Regional Clinical Genetics Services. This will also be completed by April 2025. 

NIHR Be Part of Research is an online service that helps members of the public understand what research is, what taking part might involve, as well as helping people find research studies and volunteer to take part. Last year we worked with the rare diseases community to look at how well NIHR Be Part of Research works for people living with rare conditions and to identify what improvements could be made (action 27). The findings of this are now being implemented. Two new conditions have been added and a wider review of conditions underway. Proposed changes are tested with people living with rare conditions.

The Early Access to Medicines Scheme (EAMS), the Innovative Licensing and Access Pathway (ILAP) and the Innovative Medicines Fund (IMF) are access pathways across the regulatory and access system designed to support innovative treatments being available to patients who need them earlier. Further information on these pathways is available in annex A. We are collaborating across the regulatory system - with the MHRA, NICE and NHS England - to review the effectiveness of these pathways for rare diseases (action 25). We are grateful to the Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA) who conducted a survey of their members to understand experience of engaging with these pathways. The survey created a rich picture of the experiences the life science sector of these access pathways specifically for rare disease treatments, including some challenges around UK launch decisions.

In 2024, NHS England, NICE and MHRA attended a meeting with BIA, ABPI and wider representative from industry, to discuss the findings of the survey and rare disease specific challenges faced in developing and accessing new therapies. We are grateful to the patient and clinical representatives who attended the meeting, bringing valuable insights on access to treatments. MHRA, NICE and NHS England have produced a joint written response to the survey which is included in annex C. NHS England, NICE and MHRA will meet annually to continue to discuss progress and the role of EAMS, ILAP and the IMF in supporting access to treatments for people living with rare diseases. These meetings will include representatives from patient advocacy groups, industry and clinical researchers. The next of these meetings will happen in summer 2025.

The Innovative Devices Access Pathway (IDAP) pilot is also being reviewed for effectiveness for rare diseases (action 34). To qualify for IDAP, products needed to target conditions that are life-threatening or seriously debilitating while also fulfilling a significant unmet clinical need. Despite this criterion, the pilot did not receive applications focused on rare diseases. While none of the selected technologies are directly relevant to rare diseases, the evaluation of the pilot will consider what action can be taken to implement these learnings into any future programme.

NHS England has developed a strategic approach to commissioning ATMPs (action 12). This involves horizon scanning across a 3-year horizon so that it can be understood when therapies are likely to be available following a NICE recommendation so services can be effectively planned. As summarised in section one of this action plan, DHSC has now stood up an ATMP co-ordination group to drive progress across the system.

Underpinning themes 

Patient voice

Engaging with the rare disease community and including the voice of people with lived experience in developing, monitoring and delivering actions continues to be central to our approach. There is no one fixed experience of living with, or caring for someone with, a rare disease, and we are committed to including a broad range of different voices.

In DHSC we have engaged with our patient advisory group, supported by Genetic Alliance UK, to gather the views of people from lived experience at multiple points during development of this year’s action plan, and reflect these in development of new actions. Last year, we formalised our relationship with Genetic Alliance UK through provision of a grant to support their ongoing policy engagement across over 200 rare disease organisations. We have also continued our collaboration with Breaking Down Barriers to help us reach diverse and marginalised communities. In February 2025 we co-hosted a workshop led by Breaking Down Barriers to provide input into the 10 Year Health Plan for the NHS.

The UK Rare Disease Forum continues to be a platform where policy makers, delivery partners, clinicians and representatives of lived experience can discuss actions across the 4 nations in a collaborative and constructive way. The forum has also fed into the drafting of this action plan. In addition, at its meetings it has covered a range of deep dives (in-depth discussions) to improve cross-nation understanding of issues facing the rare disease community, including on access to mental health support, health inequalities and using data to improve the lives of people living with rare conditions. The associated online platform is open to anyone who is interested in rare disease policy and is an opportunity for discussion and engagement between our stakeholders and delivery partners. Under the UK Rare Diseases Forum there is a mechanism to set up independent advisory groups (IAGs) on specific topics, and the call for proposals to form IAGs remains open.

The first IAG was set up to advise on the development of quality standards for rare diseases. This first IAG resulted in a funded project which is now working on the development of quality statements. Across 2024, a literature review was carried out to summarise the existing evidence around good care and treatment for rare diseases. This review produced a set of candidate statements, which were reviewed and revised by the steering group. The project has now progressed to the public consultation stage - the first of a series of surveys and consultation workshops has recently been held, to capture perspectives from across the rare disease community. Once the project has produced its final set of statements, NICE will look to use the statements as the basis for producing a quality standard for rare disease. Identifying commonalities across the more than 7,000 identified rare diseases to develop standards would drive quality improvement across multiple rare disease groups.

A second IAG on raising awareness among healthcare professionals has been established. This IAG will work to harmonise a 4-nation strategy to increase clinical professional understanding of rare disease as a single discipline, with a longer term objective of using the results to influence training regulators of healthcare professionals, starting with the Medical Licensing Assessment implemented by the GMC. Work commenced in late 2024, and progress will be reported through the UK Rare Diseases Forum and in the 2026 final paper for England’s rare diseases action plans.

Our delivery partners also continue their own engagement activities. Examples include NICE exploring how they collaborate with other producers of high-quality guidelines to ensure its portfolio meets the needs of the health system. Collaborating with others may involve NICE recognising external guidelines, including guidelines developed for rare diseases. NICE is currently working with DMD Care UK on their guidelines for people with Duchenne muscular dystrophy. NICE’s work with DMC Care UK will be evaluated to help inform future collaboration.

MHRA continues to engage with the patient community when assessing new therapies for license, such as in the authorisation of Casgevy in 2024 for sickle cell disease and transfusion dependent thalassemia. The NHS England Genomic Education Programme continues to engage with people with lived experience of the genomic testing process through the Patient Advisors for Genomic Education (PAGE) group. The role of the PAGE group is to:

• input to the GEP’s work plan and proposals for education and training initiatives
• provide insights and feedback during the development of educational content and GEP communications campaigns
• participate on a voluntary basis, in recorded interviews, case studies and blog articles that tell patient stories

National and international collaboration

The small numbers of people with individual rare diseases make collaboration essential. The UK is committed to building national and international connectivity so that data and expertise can be shared for benefit of people living with rare diseases, and we encourage continued collaboration between the rare diseases community based in the UK and in other countries.

The World Health Organization (WHO) Global Network for Rare Diseases (GNRD) aims to achieve a goal where all persons living with a rare disease have access to a timely and accurate diagnosis and safe and reliable quality care. We continue to offer our support to the network, WHO and Rare Diseases International as the GNRD continues to gather regional networks of expert centres and create ‘clusters’ of rare diseases research. The GNRD aims to enable the exchange of experiences, facilitate capacity building and training on rare diseases, as well as cross-border virtual advice and consultation. A virtual platform has been established and is operational. The next steps are to make the platform available to a broader audience, pending resourcing and appropriate administration. Two working groups, each with a specific technical focus, will be set up in the next year, aiming to bring together policymakers, healthcare professionals and people with lived experience. We are also engaging with the proposed World Health Assembly Resolution on Rare Diseases.

In September 2023, it was announced that the UK will be participating as a fully associated member in Horizon Europe for Horizon Europe projects funded from the Horizon Europe 2024 budget onwards, for the remaining life of the programme to 2027. We have continued to engage with the Horizon Europe initiative ERDERA (the European Rare Diseases Research Alliance), and UK representatives attended the kick off meeting in autumn 2024. Eight UK organisations are actively participating, funded by the UK government’s Horizon Europe Guarantee owing to the timing of the call. For future calls, the UK will participate as a fully associated member. The UK International Mirror and Action Group for Rare Diseases (RD-IMAG) continues to ensure national co-ordination of rare diseases stakeholders to facilitate the alignment between national and international activities.

We acknowledge that the loss of full membership of the European Reference Networks has had an impact on international collaboration. In the spring of 2024, we held a survey across rare disease clinicians, researchers, representatives of charities or patient support  organisations, and administrators, to assess the impact of leaving the European Reference Networks. The majority of responders reported decreased ability to engage with ERNs following EU exit, but that the ERN with which they are or were engaged remained open to participation from the UK in some way. We encourage that collaboration with the ERNs remains open, and are working with RD-IMAG to continue to explore options for strengthening UK relationships with ERNs and to support European research into rare diseases.

Collaboration at all levels across England, Northern Ireland, Scotland and Wales remains an underpinning priority. DHSC works closely with colleagues across the devolved nations to ensure policy on rare disease is aligned across the UK, and that we share best practice and areas of learning. Our high-level strategic co-ordination group, the UK Rare Diseases Framework Strategy Board, has held 2 meetings to discuss:

• implementation progress and engagement plans
• feedback from UK stakeholder engagement groups
• deep dives on medicines repurposing
• access to mental health support
• equality, diversity and inclusion (EDI)
• health disparities in rare disease
• using data to improve the lives of people living with rare conditions

Deep dives aim to highlight particular areas of challenge and lead to ongoing activity, for example as highlighted in the box ‘Using existing medicines in a new way to treat rare diseases - navigating a path to patient access’.

Pioneering research

The Rare Disease Research UK Platform (RDR UK), a £14 million investment over 5 years from the MRC and NIHR, announced in 2023, is now established. The platform is made up of 11 UK-wide research nodes based at various universities across the UK, and a co-ordinating hub, which is a partnership between Newcastle University, the Newcastle upon Tyne Hospitals NHS Foundation Trust and Genetic Alliance UK.

The hub is tasked with bringing cohesion across RDR UK and integrating the whole platform within the wider UK rare disease eco-system. Now established and positioned well within the rare disease research landscape, the focus for the platform going forward will be to seek to address key topics and challenges faced by the 11 research nodes and the wider rare disease research community, working alongside key organisations nationally and internationally.

MRC centres of research excellence

In December 2024 the MRC announced its first 2 centres of research excellence (MRC CoREs), which will develop transformative new advanced therapeutics for currently untreatable diseases. The new MRC CoREs will receive up to £50 million each over 14 years. The centres will build on the huge progress made in genomics, allowing the genetic basis of many diseases and processes to be identified. Advances in genome editing and other gene therapies have also made it possible to develop treatments for previously incurable conditions.

The MRC CoRE in Therapeutic Genomics aims to transform the diagnosis and treatment of genetic disorders by enabling the mass development of cutting-edge genetic therapies. The centre aims to develop processes to take successful genetic therapies and re-programme them to treat many devastating genetic disorders that are currently untreatable, such as:

• rare disorders that cause severe seizures and neurodevelopmental delay in infants
• certain types of blindness and immune disorders
• severe neurological disorders such as Huntington’s disease

UK Rare Diseases Research Landscape report

In 2023 the UK Rare Diseases Research Landscape report was published, mapping research into rare diseases across the UK for the first time (action 15). The report found a significant breadth and depth of rare disease research at sites across the UK, across a range of specialisms, and that government, industry and charities all play a significant role in funding and supporting rare disease research. However, the report also found gaps - while there were some rare diseases with multiple associated research awards, there were many which had no research awards associated over the timescale of the report.

In 2024 the steering group that supported the publication of the landscape report re-convened to discuss the findings and identify strengths, opportunities and areas of unmet need. In autumn 2024 DHSC hosted a series of workshops to communicate outcomes of the report and understand views of the rare diseases community on research gaps and priorities. This was supported by the James Lind Alliance, although not following the methodology for a full priority setting exercise. These workshops included discussions of 12 research themes, based on opportunities or gaps found through the research report and the steering group. A summary of findings of the workshops are published in annex D.

This year we will follow up by holding a similar workshop with industry and charitable funders of research. These findings will be disseminated to inform the work and strategies of research funders across the rare diseases space, including to ensure the patient voice is embedded into future work.

HealthTech Research Centres

Launched in 2024, NIHR HRCs are centres of excellence that accelerate the development of healthcare technologies to improve the effectiveness and quality of health and care services. They do this by helping medical device, digital technology and diagnostic companies (collectively known as healthtech) to develop, evaluate and validate new innovative health technologies to address pressing health and care challenges. Several HRCs are involved in work on rare disease, including:

• HRC Brain Injury, which plans expansion of research on the genomic screening for the diagnosis of rare childhood diseases
• HRC Paediatrics and Child Health - research on long-term conditions and rare diseases in childhood
• The HRC in Diagnostic and Technology Evaluation - enabling earlier interventions, reducing healthcare costs and ensuring equitable access to reliable tests

NIHR BioResource

The NIHR BioResource comprises more than 300,000 recallable volunteers, with and without health conditions, who have consented to participate in research investigating the links between genes, the environment, health and disease. This includes 2,619 new rare disease patients and relatives across 55 different rare diseases recruited into the Rare Diseases BioResource in 2024, taking the total to more than 25,000 rare diseases participants.

Case study: sickle cell disease (SCD) and thalassaemia

Blood transfusions are lifesaving for patients with major bleeding or profound anaemia but are limited by availability of donated blood. Individuals with SCD, thalassaemia and other rare inherited anaemias depend on regular blood transfusion. However, national blood supply is limited by blood donation, and the need to match blood between donor and recipient can limit the capacity to transfuse. NIHR BioResource has a programme of work involving both recall studies and use of samples to support the national blood transfusion service in the UK. On top of molecules in red blood cells that determine an individual’s blood group, there are others that are usually only important in people exposed to them through regular transfusions. This is particularly the case in patients with SCD or thalassaemia, who are typically from minority ethnic backgrounds.

In collaboration with NHS Blood and Transplant (NHSBT) and the STRIDES trial, over 75,000 blood donors in the NIHR BioResource, including many from minority ethnic backgrounds, had their blood groups determined by standard serology and genetic testing. This provided proof of principle that genetic testing can be used accurately for blood matching.

An international consortium (the Blood transfusion Genomics Consortium) then developed bloodTyper, a rapid genotype test for blood matching. The improved matching of blood that can be achieved with bloodTyper is vital for the approximately 18,000 UK individuals with SCD and thalassaemia, who can experience severe transfusion reactions.

Patients with SCD and thalassaemia can now access the new blood group genotyping test through the NHS England genotyping programme. Additionally, the NIHR BioResource has launched a new initiative focusing on the recruitment of participants with SCD and thalassaemia through its Improving Black Health Outcomes (IBHO) programme to further drive research into these rare conditions and improve health outcomes for everyone.

NHS England has also made progress with supporting persons with SCD experiencing an uncomplicated vaso-occlusive (VOC) crisis get quicker access to pain relief and specialist care as per NICE guidance. Seven sickle cell disease emergency department bypass pilot sites have been mobilised to support patients experiencing an uncomplicated VOC avoid long waits in emergency departments and get access to pain relief in a safe and timely manner. When fully operational this will support 2 in 5 people with sickle cell having painful crisis. There is also ongoing work to ensure all patients have digitised care plans which are accessible by healthcare practitioners.

Digital, data and technology

Data can be used to improve the lives of people living with rare conditions, through better understanding of the rare diseases population and producing evidence for decision-making and target interventions. The planned shift from analogue to digital in the 10 Year Health Plan highlights the importance of making the best use of data, as discussed in section 1. Enabling accurate, timely and safe access to reliable data on rare diseases is vital to designing and improving services for people living with rare conditions, as well as enabling research and access to new therapies through clinical trials. Digital, data and technology continues to be an underpinning theme of the framework, aligned to policy shift from analogue to digital to reform the NHS.

Enabling secure access to high quality, curated health data is key to driving forward life-saving research, generating new discoveries and easing the pressure on our health service. DHSC and NHS England have committed to a system of ‘data access as default’ for the secondary uses of NHS health and social care data. This continues to be facilitated by the implementation of secure data environments (SDEs) across the NHS in England. 

The Data for Research and Development (Data for R&D) Programme is designed to power life-saving research and treatments, through a network of NHS research SDEs, where researchers come to the data, rather than data leaving the NHS. The NHS Research SDE Network delivers sustainable, secure, rapid access to the world’s largest linked health datasets to support a thriving health data ecosystem that enables rare disease research that improves care, boosts innovation, and helps to sustain the NHS. The SDE Network uses state of the art tools to enable secure and rapid access to the world’s largest linked health datasets, bringing together data that has previously been fragmented to support innovative research. The SDE Network is supporting sustainable access to data by adopting data standards that are key to interoperability and developing our data pipelines and service catalogue to make data rapidly discoverable through the SDE Network’s collection on the health data research (HDR) UK Health Data Gateway. 

The NHS England SDE provides national scale coverage of highly curated, high value datasets including rare diseases. These data sets, when accessed alongside our regional SDEs that collectively cover all of England, provide access to granular, near real-time, multimodal data bolstered by clinical and data science expertise that supports data curation and the translation of research into practice. 

Professor Cathie Sudlow’s independent review of the UK health data landscape, titled Uniting the UK’s Health Data: A Huge Opportunity for Society was published on 8 November 2024. The review sets out key recommendations for safe and secure use of health data to improve lives, and calls for a UK-wide approach. DHSC and NHS England are taking full consideration of the recommendations over the coming months, in the context of the upcoming Life Sciences Sector Plan and NHS 10 Year Health Plan with the overall ambition subject to Spending Review negotiations. In particular, Professor Sudlow’s findings and recommendations will be used to develop a plan for a national health data research service, and to support current and future health research across the UK. 

This year, the UK Rare Diseases Forum and Framework Delivery Group have held deep dives on the use of data. We have also set up a steering group within DHSC for the National Disease Registration Service, reflecting the importance of this resource.

Wider policy alignment 

While the framework and action plan represent the government’s primary commitments to the rare disease community, they are also closely aligned with wider initiatives. This government’s continuing commitment to the 4 priorities of the framework is set in the context of wider activities to reform the NHS, such as the 10 Year Health Plan, the life science industry plan, and acting on the findings of the Lord Darzi review. In addition, other policy areas intersect with rare diseases, such as the mental health strategy.

While the UK Rare Diseases Framework and annual England rare diseases action plans focus on improving outcomes for people living with rare diseases as relates to provision of healthcare services, we acknowledge the importance of wider determinants of quality of life as identified in Metabolic Support UK’s report Thoughts into Action. This report found that participants often had a ‘net’ supporting them to live well with a rare disease. Factors that contributed to this net were identity, employment and benefits, nutrition, healthcare and mental health.

This government is committed to boosting opportunity and to championing and protecting the rights of disabled people, including those living with rare diseases. We will work closely with disabled people, their representative organisations and across government, so that their views and voices will be at the heart of everything we do. To support this, on International Day of Persons with Disabilities 2024 the government announced the creation of the Lead Ministers for Disability. Chaired by the Minister for Social Security and Disability, this new ministerial network will help to champion disability rights across every department and through the government’s long-term missions.

As part of the health mission to build an NHS that is fit for the future and that is there when people need it, we are taking steps to improve the provision of mental health services so that high-quality services are available when people need them. This includes recruiting an additional 8,500 mental health workers to reduce delays in waiting times and provide faster treatment, which will also help ease pressure on busy mental health services. Mental health professionals will also be rolled out in every school in England so that common mental health conditions can be identified early on and prevented from developing into more serious conditions in later life.

We recognise that the Mental Health Act 1983 is out of step with a modern mental health service, particularly failing to give patients an adequate voice in their care and treatment. The Mental Health Bill, which was introduced to Parliament on 6 November 2024, will deliver the government’s manifesto commitment to modernise the act and make it fit for the 21st century. It will give patients greater choice, autonomy, enhanced rights and support, and ensure everyone is treated with dignity and respect throughout treatment. The bill will redress the balance of power from the system to the patient and ensure people with the most severe mental health conditions get better, more personalised, care. It will limit the scope to detain people with a learning disability and autistic people under the act.

As discussed in section 1, the 10 Year Health Plan will focus on the 3 shifts needed to deliver a modern NHS:

• hospital to community
• analogue to digital
• sickness to prevention

This is a long-term challenge and will take time to deliver, and the first step was the independent external assessment of the current state of the system led by Lord Darzi of Denham published on 12 September. We know that the rare disease community faces challenges accessing health and social care that are specific to rare diseases, exacerbated for people with rare diseases, or shared with the wider population. The 10 Year Health Plan aims to ensure a better health service for everyone, regardless of condition or service area.

Health equity

Many people living with rare conditions and those who care for them report inequitable access to healthcare and other services. We are committed to addressing all sources of inequity and building a fairer system.

Core20PLUS5 is the NHS England approach to inform action to reduce healthcare inequalities at both national and system level. The approach defines a target population - the ‘Core20PLUS’ - and identifies 5 focus clinical areas requiring accelerated improvement and smoking cessation as a cross-cutting theme.

We have progressed developing a plan to include rare diseases in NHS England’s Core20PLUS5 framework (action 28). The NIHR funded Exeter Policy Research Programme Evidence Review Facility has carried out a scoping review, which systematically gathered together published research and grey literature describing the nature and extent of health inequalities experienced between the rare disease community and the general population, and within the rare disease community, with respect to receipt of a diagnosis and access to services. As part of this work an advisory group was established, with representation from people with lived experience. A summary of review is published as annex E to this report and has also been submitted for publication in an academic journal.

We continue work to understand how these findings can be used to support ICBs to address health inequalities under the NHS England Core20PLUS5 framework. The Exeter Policy Review Programme Evidence Review Facility is working on a follow up output which will map the identified inequities in the scoping review onto an explanatory framework, findings from which will be shared by summer 2025.

Within the specialised commissioning portfolio, there are over 80 highly specialised services (HSS). These HSS are delivered in a small number of centres, which are commissioned by NHS England for their experience and expertise in the management of rare diseases. The services typically have small caseloads of patients, usually no more than 500. We are working hard to reduce inequalities for patients within NHS England HSS. NHS England is publishing and disseminating a health inequalities toolkit for HSS, using feedback received from these services (action 35). The toolkit will be published in 2025.

Every 3 to 4 years, the HSS team reviews the geographical spread of patients using NHS England commissioned HSS to ensure that all patients have access and are not disadvantaged (action 36). This year NHS England mapped and measured the geographic spread of patients accessing HSS by calculating the systematic component of variation (SCV) to assess whether there is systematic variation greater than expected by chance. Further details of this exercise are included in annex A. Findings were presented to the Highly Specialised Services Oversight Group in November 2024 and the NHS England Rare Diseases Advisory Group in January 2025. Where the analysis found unexpected variation, providers have been asked to develop action plans to address these inequities. Providers who have been successful in reducing variation have also been asked to share this good practice.

Equitable access to genomic testing

Data sources are being collated to enable detailed investigation of equity of access to the genomic testing that is available for all eligible patients, recognising that there are pockets of unmet need, and these need to be identified and appropriate action taken.

In 2024 NHS England established an NHS Genomics Ethics, Equity and Legal Advisory Group to provide expertise on ethical and legal themes within the NHS GMS, while also ensuring that the NHS GMS provides equitable access to all patients. The group brings together experts from a broad range of the academic community: policy groups, representatives from each NHS GMS geography, NHS England, and independent bodies.

As part of the work being supported by the group, NHS England and the NHS Race and Health Observatory (RHO) have partnered to undertake research on identifying and assessing inequalities that may exist within the NHS GMS. Following an invitation to tender process, in December 2024 the NHS RHO and NHS England announced an 18-month research project had been awarded to investigate the disparities faced by ethnic minority patient groups across access to, and delivery of, the NHS GMS. This collaborative project will be delivered through a partnership involving the South East NHS GMS Alliance, Oxford University, Central and South NHS GMS Alliance, and the NHS RHO. Together the team will examine racial and ethnic biases in genomic service access and delivery, addressing where disparities and barriers exist thorough the undertaking of national and regional assessments of ethnic health inequalities in patient pathways. The project will inform the work of the NHS Genomics, Ethics, Equity and Legal Advisory Group.

Focus areas

In the 2023 and 2024 England rare diseases action plans we highlighted 6 focus areas which, within the priorities of the UK Rare Diseases Framework, remained of key concern to the rare diseases community. Following specific actions in 2024, activities have been embedded across the actions taken by our delivery partners. Here we highlight this work.

Support for people with undiagnosed conditions

The Genomics England Clinical Research Interface continues to yield new diagnoses for people with rare genetic conditions that have proved difficult to diagnose. 1,360 new, complex diagnoses were returned to the NHS in 2024 to inform the most appropriate clinical care. Both Genomics England and the NHS England rare and inherited disease genomic network of excellence (see above, ‘NHS Genomic Networks of Excellence on rare and inherited disease’) continue to develop new testing approaches, especially for those patients with a suspected rare disease that remain undiagnosed using current genomic testing in the NHS Genomic Medicine Service. This includes looking at novel technologies such as proteomic, transcriptomic, epigenomic or metabolomic approaches, as well as novel analytic approaches.

This is further supported through the Rare Disease Research UK platform, through its Epigenomics of Rare Disorders and Lipidomics and Metabolomics for Rare Disease Diagnosis Nodes. It is important that all people, including those whose conditions prove difficult to diagnose, are well supported while they await diagnosis. During 2024 NHS England has taken forward work towards commissioning new SWAN centres (see action 5 in the Priority 1 section, above), piloting approaches for improved care for patients with undiagnosed conditions.

Support for people with non-genetic rare conditions

As described under priority 2, the NHS England Genomics Education Programme has made significant progress in improving the non-genetic rare disease content across its portfolio. Championed by RAIRDA and with engagement from NICE, work has continued towards developing a rare diseases quality standard.

In December 2024 Parliament debated rare autoimmune rheumatic diseases, highlighting both the unmet need and the work underway to address this.

Regional specialised networks, such as the Eastern Network for Rare Autoimmune Disease, are examples of good practice in supporting people with non-genetic rare conditions. The network provides a forum for rheumatology leads across different trusts to discuss diagnosis and management for rare autoimmune diseases, bringing together expertise and sharing best practice. The network has also innovated in the use of video-conferencing for prescribing drugs for autoimmune diseases. This is important in treatment of conditions where low numbers of individual patients mean experts might not be present in local practices.

Co-ordination of care, including transition from paediatric to adult care

Our work to address the challenges associated with broader co-ordination of care is described under priority 3 of this action plan. Last year we partnered with NICE to seek feedback on how the NICE quality standard on transition from children’s to adults’ services could be adapted to ensure it is relevant to the needs of the rare diseases community. NICE updated the quality standard, including adding a new statement on a transition plan, and published this in December 2024. NHS England has finalised its healthcare transition framework, which supports young people’s transfer into adolescent and adult services. The publication is due to be uploaded onto the NHS England website in early 2025.

Mental health support

People living with rare conditions and their families and carers often face significant challenges with access to mental health and psychological support. Mental health services should be offered based on need and should not exclude anyone because of a particular physical health or neurological diagnosis. Significant steps are being taken nationally to improve access to mental health services, which are described in the wider policy alignment section of this action plan.

In the 2024 England Rare Diseases Action Plan we described the work that NHS England was doing to embed resources to educate the workforce in mental health and psychological services to support those living with rare conditions, their families and carers. This included establishing a GeNotes psychiatry working group to develop content in both the genetics of mental health and the psychological requirements and holding a series of webinars. This now includes 10 tier 1 and associated tier 2 resources. The mental health specialty collection will be launched in May to coincide with Mental Health Awareness Week. The tier 2 resources in the knowledge hub around rare disease and mental health have been created in association with our partners M4RD. Of particular relevance are:

• Mental health and rare disease
• Introduction to rare disease
• The diagnostic odyssey in rare disease
• Rare disease patient advocacy groups

Improving clinical research delivery for rare diseases

To maximise our potential to be a world leader and develop a more competitive, efficient and accessible clinical research system, which should also better support clinical research for rare diseases, DHSC is committed to implementing recommendations from the Lord O’Shaughnessy independent review of commercial clinical trials in full. Going beyond this, our priorities are to:

• streamline and reform the set-up and delivery of clinical trials, including making trials more accessible to participants via digital means
• drive a ‘right research, right setting’ initiative, to include a radical move to research delivery in primary and community care
• move from a reactive to a proactive ‘prevention’ model of portfolio management, including supporting the workforce and continuing to embed a research and innovation culture across the health and social care system

As detailed in action 38, reform of clinical trials regulations aims to ensure the UK remains a competitive location for cutting-edge clinical research.

Registries

Stabilising and maximising the potential of rare disease registries and the importance of being able to collect, securely store and safely use data continues to be a policy priority. As in 2023, the congenital anomaly and rare disease registries of all 4 nations of the UK have continued to meet regularly to share best practice and agree consistent approaches where possible.

NCARDRS is an important resource, and provides vital data for clinicians, researchers and policy makers on congenital anomalies and rare diseases, including in the delivery of several actions within the action plan. However, due to resource pressures seen throughout the NHS, some activities have needed to be paused, such as self-reporting mechanisms for people living with rare conditions to submit their own data, and a follow-up workshop on future opportunities.

We acknowledge that registries held outside of government, such as those held in the charity sector or by researchers, are also important sources of data which is often well curated and able to support clinical research for rare diseases.

Monitoring and evaluation

This is the fourth England Rare Diseases Action Plan under the UK Rare Diseases Framework. As well as driving forward actions, it is equally important that we are able to determine whether the interventions we are putting in place are effective and making a difference for people living with rare conditions.

We have commissioned a portfolio level evaluation of England’s rare diseases action plans with input from the rare disease community on design of metrics (action 29). This work is funded via the NIHR through a 2 year contract running from May 2024 with Consilium Scientific and Realise Advocacy alongside the research to understand the diagnostic odyssey (see action 17 above). This evaluation has made notable progress, with the Research Advisory Group and the Patient and Public Involvement and Engagement group successfully established in July 2024, providing a strong base for collaborative decision-making. An evidence review was completed as scheduled in September 2024, ensuring a solid foundation for the next phases of the research. The launch of an eDelphi exercise is scheduled for March 2025.

Evaluating the influence of the framework will tell us whether the interventions over this 5-year period have been effective in making a difference to what matters most to the rare diseases community and will help shape future rare diseases policy.

Future directions

This is the final year of the 5-year UK Rare Diseases Framework, published in January 2021. We are enormously grateful to those across the rare diseases community who have engaged with us over the first 4 years to help us understand the challenges and develop actions to address them. We look forward to continuing this collaboration in the year ahead as we reflect on what has worked and where the unmet need remains. In February 2026 we will publish a capping paper reporting on delivery against remaining live actions of the total of 39 we have set out over the last 4 years.

Over the next year we will be looking at ways to build on the progress made over the past 5 years. The framework is UK-wide and so we will also be exploring ways of working across the devolved administrations as we look towards the future of rare diseases policy. And of course we will continue to engage with people living with rare diseases and those who care for them to ensure we embed their voice in all we do.