UK ambitions in rare disease research


In 2014 the 100th orphan-designated drug received a marketing authorisation in the EU. Alongside this landmark, initiatives such as the rare disease registry and the 100,000 Genomes Project in the UK continue to improve the outlook for patients. David Bennett reviews progress on these two projects.

Speaking at a February reception held in the House of Commons, organised by Rare Disease UK to mark Rare Disease Day 2015, Earl Howe, the government minister responsible for quality at the Department of Health (DH), highlighted some of the advances since the government implemented its Strategy for Rare Diseases in November 2013. Of these, the rare disease registry and 100,000 Genomes Project are highly ambitious and long term in nature.

Rare disease registry

One of the major bottlenecks in developing new treatments for rare, non-cancer, disorders is often recruitment of patients for clinical studies. For companies selecting trial centres the prospects of finding patients to meet their development timetable is top of mind. For this reason, a sizeable cohort of eligible patients is likely to make the UK a more attractive proposition and give patients earlier access to medications. Beyond disease-specific treatment, patients can benefit from an earlier diagnosis in other ways: avoidance of inappropriate treatment, including surgery, and appropriate treatment of symptoms.

"The registry framework should be in place by the end of 2015 so that every diagnosis of a rare disorder can be recorded"


Registries for collecting congenital anomalies have evolved over time in the UK on a regional and disease-specific basis. However, only half of births are currently captured within these registries. The planned rare disease registry has the aim to provide additional resource to improve ascertainment and develop a single national database. Once in place, this Congenital Anomaly and Rare Disease Registration Service should support the 100,000 Genomes Project, inform decisions relating to health service provision and enable rare disease research. The registry framework should be in place by the end of 2015 so that every diagnosis of a rare disorder can be recorded.

Within Europe there are approximately 600 patient registries, according to the Orphanet audit. France boasts the highest number of registries (132), followed by Germany (116). In the UK there are 87 registries. A number of these registries cross borders and are organised on a regional, European or global basis. The intention with the proposed UK national registry is to integrate effectively with other, existing registries.

The obstacles to integration should not be underestimated. Each of these initiatives would have been designed with specific goals in mind. A number of them, particularly industry-sponsored observational surveys, collect values over time on a wide range of variables, beyond that required for a pure registry. The data collected permits fundamental research. Particularly relevant to highly rare, 'ultra' orphan, conditions is the ability to gain a sufficient understanding of the natural history of a disorder in order to provide a baseline comparison for clinical studies. For these reasons disease-specific databases are likely to proliferate. Consenting and technical obstacles need to be addressed if patients are to be entered into two databases.

"The proposed register also needs to be complemented with other initiatives in patient identification particularly for many of the ultra-orphan conditions which pose diagnostic challenge"


The proposed register also needs to be complemented with other initiatives in patient identification particularly for many of the ultra-orphan conditions which pose diagnostic challenge. In the UK neonatal screening is performed for nine conditions, an increase from five when maple syrup urine disease, homocystinuria, isovaleric acidaemia (IVA) and glutaric aciduria type 1 were added to the list in January 2015. The number of disorders would have to be significantly expanded to cover genetic conditions for which specific treatments are available or are in development.

100,000 Genomes Project

The remit of this project is to deliver the sequencing of 100,000 complete genomes of patients with rare diseases and cancers. In addition to the patient with a rare disease, the genomes of two of their closest relatives will also be sequenced. Launched in 2012, the target completion date is 2017. Eleven centres have been selected to deliver the project and to date a little over 2,000 patients have been recruited.

One of the designated centres is Southampton. Karen Temple, Professor of Medical Genetics at the University of Southampton commented on the immediate benefits of participation: "...for some participating patients, there will be a conclusive diagnosis that can be reached for a rare and inherited disease that was not possible before. Treatment for cancer will now be targeted at the particular genetic changes that are present, which will improve outcomes."

In addition to gaining insights into disease associations, the wider purpose of the project is to enable the NHS to incorporate genomics into routine patient care. The programme is under the stewardship of Genomics England, wholly owned by the DH. A complementary organisation, Health Education, will be established to ensure that NHS staff are trained in the relevant skills to apply the health science insights gained from the programme in everyday practice.

Funding treatments

The strategic objective of the UK's rare disease plan is to make the UK the best place in the world to conduct research into rare diseases. Certainly, the UK government initiatives will go a long way towards fulfilling that goal. At the same time, for research-based companies developing orphan drugs, most of which are based abroad, an important factor will be a coherent and fair system for funding orphan drugs after they receive marketing authorisation. The call by the leading patient support group, the MPS Society (The Society for Mucopolysaccharide Diseases), to reinstate the previous body, the Advisory Group for National Specialist Services (AGNSS) responsible for advising on the provision of highly specialised treatments, had attracted over 2,000 signatures for its petition by the start of March. In the meantime, for companies with a licensed orphan drug, the process of bringing their new treatment to patients who need it remains complex and time-consuming.

About the author:

As part of an extensive career in pharmaceutical marketing, David Bennett has had a primary focus on rare disorders for many years. This involvement started with the medical marketing of human growth hormone in the late-1980s. Dealing with funding issues during a period of changing NHS structures was a standard feature of his work. From the 2000s onwards, with the first orphan drug launch (for Fabry disease), he has supported clients in the orphan sector, working with relevant disease communities and developing programmes aimed at patient detection, referral, advocacy, medical education and reimbursement. He now provides services on a freelance consultancy basis.

Read more on rare diseases:

Funding rare disease treatments in the UK – navigating the labyrinth

First patients diagnosed in 100,000 Genomes Project


Linda Banks

12 March, 2015