Rare disease and orphan medicines – Will government policy change the paradigm?

Angela McFarlane, Vice President, Strategic Planning, North Europe, IQVIA talks about orphan and ultra-orphan diseases, and the diagnostic odyssey which many are forced to undertake
There is nothing rare about rare diseases, and 3.5 million people in the UK will be impacted by one at some point in their lives. The diagnostic odyssey for patients in the UK is 4-7 years.1,2
Having received a diagnosis, what is unfortunately still rare are treatments for the condition – of the 7,000 rare diseases identified, only 400 have a licensed treatment.3However, obtaining a license is only the start of the challenge – approved medicines must navigate the daunting barriers of access and adoption to realise their promise for patients. Could the Innovative Medicines Fund (IMF) be that catalyst for improving access to innovative orphan medicines, just as the Cancer Drugs Fund (CDF) has been for cancer treatments? 4
Before we explore that question, let’s look at how issues are improving for people with rare disease, namely the global leadership the UK is showing, in respect of accelerating diagnosis of rare disease.
In 2015, the National Disease Registration Service (NDRS) was set up to develop and run a comprehensive population-based registration service, collecting and qualityassuring data on congenital anomalies and rare diseases across the whole population in England.5 Since 2015, it has realised national coverage of over 1,400 congenital anomaly or rare disease datasets out of over 6,000 collected.
In 2013, the UK Government launched the 100,000 Genomes Project to investigate whether whole genome sequencing (which involves reading through 3 billion pairs of letters in the human genome) could help improve diagnosis and accelerate the discovery of precision medicines.6Five years later, the UK became the first national health system in the world to offer WGS to people with undiagnosed rare diseases and cancer as part of routine care. The 100,000 Genomes Project has transformed the diagnosis of the 8-in-10 rare diseases with genetic causes, and the creation of the NHS’s Genomic Medicines Service – as well as the 50-fold goal of achieving five million sequences, offering further new hope to people with a rare disease. 7
Earlier this year, Genomics England announced the Newborn Genomes Programme (NGP) in which up to 200,000 babies’ genomes will be sequenced and analysed for a set of actionable genetic conditions which may affect their health in early years.8 The programme aims to ensure timely diagnosis, access to treatment pathways, and enable better outcomes and quality of life for babies and their families. The NGP will co-design and run an ethics-approved research pilot embedded in the NHS to explore how, and whether, to offer whole genome sequencing (WGS) to all newborns, to accelerate diagnosis and access to treatments for rare genetic conditions.
On the 11th November 2021, a study published in The New England Journal of Medicine,led by Professor Mark Caulfield and Professor Damian Smedley, analysed the diagnostic and clinical impact of genetic sequencing within the NHS. 9 Analysing the genomes of 4,660 people from 2,183 families led to a new diagnosis in 25% of patients. Many of these patients have spent years enduring the diagnostic odyssey. One such patient in the study is a 10-year-old girl who endured multiple hospital visits during her seven-year journey to diagnosis at an estimated cost to the NHS of £375,000. Once the WGS had identified her underlying problem, she went on to have a bone marrow transplant which cured her disease, costing £70,000.
As a result of Caulfield and Smedley’s work, 25% patients received more focussed care, such as family screening and therapies to help manage the condition. For patients with conditions such as intellectual disability, vision, and hearing disorders, the diagnostic yield was even higher at 40-55%. This will pave the way for accelerating the discovery of precision medicines, and attract even more clinical research to the UK for paediatric and rare disease.
Figure 1:Over one third of planned UK launches in the next three years will be dedicated to orphan or ultra-orphan medicines 10F

The orphan medicines discovery landscape is transforming

In August 2021, IQVIA conducted primary market research amongst global C-Suite pharma and biotech leaders regarding the overall attractiveness of the UK for conducting clinical trials and launching new medicines, following the UK’s exit from the EU Bloc.10 Over 200 global industry leaders participated in the survey, and the results were a vote of confidence in the UK. Respondents called out the UK’s performance in respect of research and discovery of COVID-19 vaccines and treatments, and the impactful new UK Government Life Sciences Policies, from the MHRA, NICE and the Office for Life Sciences.
79% confirmed that the UK will remain a priority launch country for their company, with 74% stating that the UK would be a Tier 1 early launch country over the next three years.
The promise for people with rare diseases was even more exciting, with over one-third of the new medicines launches planned in the UK being for orphan or ultra-orphan medicines.

Changes to the approval landscape and the advent of the IMF

Headlines for breakthrough rare disease medicines, such as the triple therapy for the cystic fibrosis gene therapy, Zolgensma, which NICE ruled had an ‘exceptional impact’ for babies with severe spinal muscular atrophy (SMA), majored on deals and list price.11,12Little was reported about the time the negotiations took, and the number of other promising orphan medicines that didn’t make it over the line with either NICE or NHS England, due to the unique challenges orphan medicines face in research and data generation. Consequently, over the last five years, patients living with rare diseases in the UK and their carers have been dissatisfied with the medicines approval processes for rare disease treatments, according to a survey of this community by the Genetic Alliance and Alexion. 13 Typically, patients believe the UK processes are unfair on those living with a rare disease, and the system is both too slow, and not resourced for rare diseases.
“ As a result of Caulfield and Smedley’s work, 25% patients received more focused care, such as family screening and therapies to help manage the condition 
Narrow eligibility requirements for the Highly Specialised Technology (HST) programme means that many treatments can struggle to secure approval from NICE for routine use on the NHS. In most cases, those that do secure approval often see their use restricted to certain subpopulations of their licence. The result is that patients in the top five European countries, such as Germany, Italy, and France, have better access to medicines than counterparts in England. Yet, England is ahead of most European countries, including Scotland, and restrictions to medicines might be valid given the evidence available.14
However, steps are being taken by Government and the NHS to reduce these inequalities, through initiatives such as the review of NICE’s methods and processes, the implementation of the Rare Disease Framework, and development of the Innovative Licensing and Access Pathway (ILAP). Former Minister for Innovation, Baroness Nicola Blackwood – who herself suffers from a rare disease and endured her own diagnostic odyssey – set up the Accelerated Access Collaborative and launched the NICE methods review and the Commercial Framework, announcing the new £500m Innovative Medicines Fund as part of the 2019 Conservative manifesto.
The IMF will seek to expand on the existing Cancer Drugs Fund (CDF) for the purpose of improving access to rare disease treatments, among others. This is an important step. No single initiative can solve the access to treatment challenges facing patients and their carers in England, but the IMF can address the fundamental issue of data uncertainty for rare disease treatments at the time of their first assessment by NICE.
The IMF could be a catalyst for improving access to orphan medicines. However, it is important to note that it should not be seen as a bypass for improvements to these medicines being approved for routine commissioning. IMF should ensure that system challenges, such as biomarker testing at the seven regional Genomic Laboratory hubs, do not further delay patients with life threatening diseases with access at a local level to these nationally approved innovations.
In March 2021, Alexion and AstraZeneca rare disease commissioned IQVIA to work with the rare disease community and thought leaders in the UK medicines access policy, on the development of a white paper. This was launched in September 2021 – The Innovative Medicines fund acatalyst for access to rare disease treatments.15
“ As a result of Caulfield and Smedley’s work, 25% patients received more focused care, such as family screening and therapies to help manage the condition 
The paper is designed to:
  • Support the rare disease community response to the public engagement exercise on the IMF, to be led by NHS England during 2021
  • Support the wider efforts of the rare disease community to improve outcomes for those with rare diseases and their families
  • Shape future policy for the IMF, and provide recommendations for NHS England and NICE to optimise design and implementation
  • Support all stakeholders who contributed to the much-anticipated consultation on the forthcoming IMF, by providing an evidence-based narrative from leaders in the rare community, and benchmark data from IQVIA.
The paper makes a series of recommendations for consideration by those finalising the IMF, to ensure that orphan medicines take their rightful place in it.
“ To drive access for patients, rare disease medicines must have the same opportunity for IMF-funded access as a medicine for any other disease 
Recommendation 1: Ambition To drive access for patients, rare disease medicines must have the same opportunity for IMF-funded access as a medicine for any other disease.
Recommendation 2: Entry and exit criteria The IMF must have clear but flexible entry and exit criteria that can accommodate rare disease medicines, as well as other medicines.
Recommendation 3: Funding IMF funding should not be ringfenced by disease area or medicine type, and must not operate on a ‘first-come, first-served’ basis.
Recommendation 4: The IMF should have a flexible budget linked to horizon scanning.
Recommendation 5: Funding for the IMF should be tabled as part of negotiations on the 2024 Voluntary Scheme for Branded Medicines Pricing and Access (VPAS).
Recommendation 6: Data collection The IMF should allow for bespoke data collection, taking a medicine-bymedicine approach to outcomes, data sources and the time required. The IMF must recognise the complexity and difficulty of evidence generation in rare diseases.
Recommendation 7: Governance An external IMF multi-stakeholder group should be formed, reporting annually on IMF performance using Key Performance Indicators (KPIs) broken down by disease and orphan status.
Alignment with other initiatives
Recommendation 8: The IMF must be aligned with the evolving access landscape, including initiatives such as the ILAP, NICE Methods and Processes Review and UK Rare Diseases Framework.
UK collaboration Recommendation 9:
The four UK nations should hold discussions to leverage lessons from the IMF – and their own funds – and explore the scope to increase the value of the evidence generated. The four UK nations should also work together to ensure access to innovative medicines, including rare disease medicines, is equitable across the UK.

Angela McFarlane, Vice President, Strategic Planning Northern Europe, IQVIA, works with the UK Government, NHS, Pharmaceutical and Biotech Industry and Patient Organisations on pioneering collaborations that will improve NHS patient access to clinical trials, RWE studies and innovative medicines. She founded the Clinical Research Coalition to embed learnings from the pandemic, the output of which became Lord Bethell’s Clinical Trial Transformation programme.
In 2018, she was nominated by Pharmaceutical Marketing Europe as one of the 30 most influential women in UK Healthcare and in September 2019 appointed by the UK’s CSO as an Ambassador for Women in Science and Engineering.