Rare diseases by their definition only affect a small proportion of people, which can often be a barrier to innovation. Clinical trials for rare diseases can prove costly and recruitment can be particularly challenging, which has historically led to a lack of interest from pharmaceutical companies.
Thankfully this is changing. Globally, governments have recognised that when rare diseases are considered collectively, they affect a much larger group of people and have a significant impact. Research shows that 1 in 17 people will suffer from a rare disease at some point in their lives; that's 3 million people in the UK and as many as 30 million people across Europe. Often, rare diseases are chronic and life threatening and they make considerable demands on the resources and capacity of the NHS and other care services.
Here in the UK, we are recognised as a leader in the research, treatment and care of rare diseases. This is no doubt down to the strength of the pharmaceutical sector and the availability of world-class experts and cutting-edge facilities supported by the National Institute for Health Research (NIHR).
The NIHR Rare Diseases Translational Research Collaboration (TRC) brings together the expertise and facilities to support fundamental discoveries and translational research in rare diseases. It provides an ideal opportunity for collaboration with industry, enabling new clinical research into poorly understood rare diseases and serving as a platform for innovative new clinical trials.
Rare diseases provide a particular opportunity to industry in drug development. The large majority of rare diseases are caused by genetic mutations in a particular gene, thus pinpointing the molecular drivers of the disease and providing strong 'in-built' target validation and stratification. Risk of failure due to lack of efficacy is therefore smaller than in "non-genetic" diseases, and clinical outcome of efficacy studies is more predictable. The gain for industry is a faster route to proof-of-concept and market for new drugs, and new indications for existing drugs through repositioning studies. Importantly, rare diseases can serve as model diseases for more common diseases by clinically validating key mechanisms targeted by new drugs in development.
The Rare Diseases TRC works closely with the NIHR BioResource – Rare Diseases, a recallable resource of participants with rare diseases, and their relatives, who are willing to participate in clinical research. This invaluable resource is intended to help identify genetic causes of rare diseases, improve rates of diagnosis and to enable studies to develop and validate treatments thus improving care for those with rare diseases and their families.
As the cohorts of rare disease patients grow, the Rare Diseases TRC will make emerging data accessible to new researchers, and focus on how patients can be helped through new studies and research, including clinical trials with industry. The Rare Diseases TRC actively supports an increasing number of collaborations across the NHS and the life sciences industry.
For example, the NIHR Office for Clinical Research Infrastructure worked with the TRC to develop a funding call for industry collaborative studies for projects that generate in-depth phenotypic information. This new information will improve our understanding of the natural history of rare diseases, how to measure their progression and use this information to develop new treatments and speed up diagnosis of rare diseases. The call, launched in January 2015, generated 29 expressions of interest from industry and has resulted in nine new studies to date, co-funded by NIHR and a range of industry partners.
Studies underway include a phase II trial to investigate whether the drug tocilizumab, which is already available for treatment of rheumatoid arthritis, could be used to treat the rare but debilitating condition pulmonary arterial hypertension (PAH). There is no cure for PAH. It is a progressive disease caused by narrowing or tightening of the pulmonary arteries which connect the heart to the lungs, causing symptoms such as breathlessness, fatigue, weakness and angina. Fewer than 40% of patients currently live beyond five years. It is hoped that by successfully targeting the inflammatory mechanisms driving PAH, tocilizumab could become the first disease modifying drug for PAH.
Another study co-funded through the industry call is investigating a new treatment option for autosomal dominant optic atrophy (DOA) - an inherited eye condition that affects the optic nerve and leads to blindness in the majority of patients. It is a progressive condition, with no treatment available that can stop the progression of vision loss.This study is investigating whether a new anti-oxidant drug could protect the optic nerve and help to preserve vision.
Through the Rare Diseases TRC, the NIHR has already invested £20 million in new research. Many of these studies wouldn't have been possible without a collaborative approach involving partnerships across academic centres and industry, both large pharmaceutical companies and much smaller start-ups.
We believe that these projects will lead to breakthroughs in new treatments and diagnostics and offer advancements in personalised medicine approaches that could also benefit other more common illnesses. This is news that will be welcomed by the UK's 3 million people with rare diseases who are hoping that their illness will be next in line for a research breakthrough.
Oliver Rausch is the Programme Director - Translational Research Partnerships in the NIHR Office Clinical Research Infrastructure.