From rare to common: The time to tackle rare diseases is now
As a paediatrician working in drug development, mother of a child with a rare disease, and founder of a medical research charity, Dr Harriet Holme understands the complexities of the rare disease landscape. Here, she argues that while balancing the interests of various stakeholders is essential, we cannot afford to delay action in the rare disease space any longer.
The scale of the problem
It’s easy to hear the word “rare” and think it implies a small problem. Whilst each rare disease affects fewer than 100,000 people in Europe, there are over 10,000 rare diseases in total. In the UK alone, approximately 4 million people live with a rare disease, and more Americans live with a rare disease than those who have HIV, heart disease or a stroke combined.
Beyond patients, these life-limiting conditions significantly impact families and caregivers, with an estimated 1 in 7 people, or 9.4 million in the UK, being affected. Globally, the number of affected individuals is staggering, highlighting the urgent need for collective action.
Thankfully, despite their distinct nature, rare diseases share many similarities in terms of their drug discovery and development pathways. These similarities mean infrastructure can be created to serve the community as a whole, fostering economies of scale and driving a new era of investment and therapies.
Unlocking the power of DNA
Early diagnosis through the Newborn Blood Spot Test significantly improves outcomes for some people with rare diseases. Diagnosis at birth can lead to better growth, improved organ function, and increased survival rates.
However, for the majority of people with a rare disease, the current diagnostic journey in the UK averages 4.7 years, with 30% of affected children dying before they reach their 5th birthday. Rapid access to genomic sequencing could reduce this time dramatically.
Currently, the Newborn Blood Spot Test screens for just 9 inherited conditions, even though the technical capability exists to genetically diagnose most rare diseases. Providing the opportunity to check for rare genetic diseases could prevent many unnecessary deaths and massively reduce healthcare costs associated with delayed diagnosis (£3.4 billion over the last 10 years).
The Newborn Blood Spot Test is primarily a screening tool, usually requiring additional diagnostic tests to confirm a diagnosis. Screening tests balance the benefit of treating a disease early against the risk of unnecessary tests on healthy individuals. For those with a rare disease, the risk of a false positive is low due to the diagnostic nature of a genetic test. While most rare diseases lack approved therapies, simply receiving a diagnosis can spare patients from the long and traumatic process of trying to figure out what’s wrong.
Offering whole genome sequencing (WGS) to symptomatic people with diagnostic uncertainty would also speed up and improve diagnosis accuracy. WGS is cost-effective and convenient for at-home testing, meaning it could similarly alleviate the lengthy and arduous diagnostic journey for many patients.
What’s more, genetic diagnosis is key for addressing both the root cause of inherited disease, and for understanding druggable pathways. In fact, genetic understanding increases the success rate of drug development by 2.6 times. The NHS Long Term Plan does aim to sequence 500k whole genomes to improve the diagnostic pathway of rare disease, but capacity issues persist.
Secondary benefits of action
For the 95% of people with rare diseases lacking approved therapies, disease modification could be life changing and yield significant additional benefits.
The economic impact of rare diseases is large and includes both the direct costs of care, together with the indirect costs such as:
Patient costs: Non-medical expenses (e.g., transportation), social productivity losses, and prescription charges.
Caregiver costs: Productivity losses (e.g., absenteeism, early retirement), non-medical expenses, social productivity losses, and uncompensated caregiving time.
Combined economic burden: Health value loss, lost tax revenues, delayed diagnosis, and disability/carer’s allowance payments.
In 2020, the World Economic Forum estimated that 350-475 million people were affected by rare diseases globally, with significant consequences in terms of lives lost and the social and economic impacts on families and caregivers.
The high economic impact of rare disease is closely linked to the direct cost of healthcare, with some of the most expensive drugs on the market targeted to treat rare diseases. Orphan drugs, which are nearly five times more expensive than non-orphan drugs, add to the economic strain and sustainability of health systems. However, evidence shows that when rare diseases are untreated, costs are 20% higher, with annual social care costs estimated at $159 billion.
Early diagnosis, such as early diagnosis of newborns, could lead to disease-modifying therapies, reducing stress and long-term costs while improving patients' lives.
Data integration for better outcomes
Creating collective datasets is crucial for transforming our understanding of rare diseases and driving new treatments. Siloed data limits therapeutic translation. To advance drug development and improve patient access to clinical trials, we must integrate data from sequencing, clinical records, and patient reported outcomes. This integration will enhance disease understanding, foster innovation, and streamline recruitment by connecting genetic identification with clinical trials.
Embedding natural history studies in routine care and capturing real-world data would also accelerate drug development and market access. Patient recruitment in rare disease clinical trials is challenging, but integrating the patient pathway from genetic identification to trial recruitment could help. If patients consented to being contacted for research at the time of sequencing, we could establish pre-recruited patient cohorts, transforming recruitment and feasibility.
Engaging the entire rare disease community is crucial for maximising the impact of this integrated data, leading to better diagnostics and therapies.
A progressive regulatory environment
Pioneering and progressive regulations are needed for rare diseases to attract investment, much like that seen in cancer.
There are two key regulatory pathways that could boost innovation and clinical development:
Shared molecular pathways: Genetic and pathway understanding to increase the efficacy of small molecule development across various diseases.
An umbrella disease pathway: Facilitating the development of therapies for genetically heterogeneous diseases that are not addressable through small molecule approaches.
These pathways would enable scalable, personalised medicine solutions and offer an opportunity for UK-based companies to take the lead in manufacturing.
An incentivised landscape ripe for innovation
Rare disease advocacy groups have always been vocal and active, with good networks and support within their community, but the landscape is fragmented. To attract attention from biopharma and biotech, governments have introduced premium pricing for rare diseases through laws like the Orphan Drug Act in the USA, Regulation (EC) 141/2000 in the EU, and the Human Medicines Regulation 2012 in the UK.
By 2026, orphan drugs will represent a fifth of prescription sales and nearly a third of the global drug pipeline's value, with top therapies being worth $3 billion to $13 billion each in 2026. In 2023, the global rare disease treatment market was valued at $152.18 billion, with projections to reach $380.62 billion by 2029.
Seventy percent of this market value is tied to drug pricing in the US, regardless of where the companies are located. Orphan drugs remain at least in part shielded from recent US pricing legislation, suggesting continued interest in this sector even as pricing pressures impact other therapeutic areas. All in all, there is huge potential to expand within the rare disease market if investment strategies can be aligned effectively.
A key opportunity for UK biopharma and biotech
Clinical trials are a gateway to medicines for patients. Rare disease clinical trials might be small, sometimes just a single patient, but the operational and administrative burden is the same as for larger studies, taking 6 months before a trial can start. This time delay means biotech companies with high-cost infrastructure will choose to pursue more common conditions over rare diseases, even though fewer than 5% of rare diseases have approved treatments.
The NHS, as the largest integrated healthcare provider in the world, generates an unmatched breadth and depth of health data as a universal, single-payer system serving a diverse population. The UK clearly has the science and infrastructure to make a difference in this field, but we must facilitate commercial investment to unlock its full potential for patients, payers and growth.
Despite representing a small part of the research landscape in the UK, commercial trials have a disproportionately large role in improving health and economic outcomes. The UK's genomics sector generates £94.2 billion in turnover and employs 282,000 people (65% outside London and the South East). Building on these genomic capabilities to invest in molecular diagnostics for addressing diagnostic uncertainty would position the UK as a global leader and a prime destination for commercial investment. Creating a national network of experts focused on rare diseases could also help streamline processes and reduce the operational burden of drug development.
At Weatherden, we understand that clinical trials fail for reasons beyond biology. By challenging the landscape of discovery and trial design, we have raised the early development success rate from the industry average of 29% to over 65%, generating $25 billion in realised value over the past seven years.
Our advanced technical capabilities, combined with efficient delivery and regulatory streamlining for rare disease trials, offer the opportunity to transform the economics of investing in rare disease drug development and bring groundbreaking new treatments to patients.
A rare chance to make a difference
The UK has the potential to become a global hub for rare disease clinical trials, attracting investment that could be reinvested to increase access to patient genotyping and improve our understanding of rare disease. Accelerating and improving trial delivery will make investments more appealing to biopharma, ensuring the rare disease population is not left behind and ushering in a new era of medicines for patients who desperately need them. This represents a tractable, scalable solution, not just for rare disease, but the future of personalised medicine.
Want to learn more about the current rare disease landscape? Join us at the upcoming Getting Cilia Moving industry accelerator day on 1st October! This event, hosted by PCD Research, LifeArc and Weatherden, will unite leaders in rare diseases, genomics, respiratory medicine, and genetic therapies to catalyse interest and collaboration in developing orphan therapies for Primary Ciliary Dyskinesia (PCD).
