The status of rare diseases in Europe

People living with rare diseases are estimated to comprise between 6% and 8% of the EU population. In other words, 30 to 40mn Europeans are afflicted – 50% and 75% of which are children. The types of ailments they suffer from vary, as more than 6,000 rare diseases exist – half of which begin in childhood. Unfortunately, patients are misdiagnosed more than once 40% of the time.

Rare diseases touch the lives of many people in significant ways: they are responsible for 35% of deaths in the first year of life, with a 30% mortality rate by the age of five. 80% of patients with rare diseases experience difficulties in completing daily household tasks and 70% of patients with rare diseases –along with their carers – have reduced or completely stopped their professional activities due to the illness.

There remain significant unmet needs for people living with rare diseases, spanning the spectrum of care from diagnosis to treatment. It takes an average of five years for a child with a rare disease to get an accurate diagnosis, even in countries with sophisticated health systems. Delays in diagnosis are devastating to a child’s – and a family’s – health and quality of life. People living with a rare disease often spend years in a ‘diagnostic odyssey’ before receiving the current diagnosis.

Based on the data from the Orphanet portal for rare diseases and orphan drugs, a diagnostic test is available for some 3,000 rare diseases, which means the majority of such diseases lack specific tests. At least 95% of rare diseases do not have any approved medicinal treatment. For many people living with a rare disease, innovative medicines are often the first treatment made available for their condition and have a considerable positive impact on longevity and quality of life. Despite the success of the Orphan Regulation in making more orphan medicines available within the European Union, substantial discrepancies exist in access to these medicines between member states.

Timely and equitable access to orphan medicines is not guaranteed in the EU. Members states vary greatly in both the number of products publicly reimbursed and the average time it takes for patients to gain access to them. Discrepancies can surpass 50% in the number of publicly-reimbursed products, and over 24 months in time to reimbursement decisions between member states.

Despite these challenges, Europe should be proud of the progress it has made in developing new therapies. The EU Orphan Medicines Regulation can be considered an unequivocal success as it has brought real benefit for people living with rare diseases in Europe. It also demonstrates that having the right incentives in place can drive investment in R&D.

Over the past two decades, there have been more than 150 orphan medicinal products approved by the European Medicines Agency (EMA) for over 90 rare diseases, up from only 8 orphan products available in 2000. The EU is spearheading global clinical research on rare diseases, providing early access to potential novel treatments for hundreds of thousands of EU patients with rare diseases each year.

Significantly, approximately 50% of the approved designations target rare conditions that lacked any previously approved treatment in the EU, while the rest provided a significant clinical benefit or major contribution to patient care over existing treatments. This progress has been fuelled by a significant increase in new clinical trials on rare diseases. The EU has seen strong growth in clinical research on rare diseases since the mid-2000s: annual activity has increased by 88% between 2006 and 2016, compared with a global average of 68% in the same period.

Beyond the incentives provided by the Orphan Medicines Regulation, further efforts are needed in order to ensure greater access to innovative therapies. Addressing the evidence gaps and the uncertainties this creates is one essential element. Additional efforts could be made to initiate early dialogue and to better leverage real-world evidence (RWE) to reduce stakeholder uncertainties and facilitate earlier patient access. To this end, it is exciting to see that Scotland has developed a new access model that addresses these challenges.

A new pathway gives early access to treatment for patients, while additional data collection can take place over a three-year period. A final decision will be taken on the routine use of a medicine once more evidence is available.

Initiatives, such as TRUST4RD (Tool for Reducing Uncertainties in the evidence generation for Specialised Treatments for Rare Diseases), attempt to facilitate a shared understanding of the challenges faced by manufacturers, regulators, health technology assessment bodies, payers and patient groups in the development and use of real-world evidence to address uncertainties for rare disease treatments. This type of initiative demonstrates that, while acknowledging the unique challenges in developing an orphan product, early dialogue between stakeholders within a shared framework can lead to a common understanding of challenges and solutions to improve patient access.

Another success at the EU level, in the area of rare diseases, has been the establishment of the European Reference Networks (ERNs). By bringing together more than 900 highly specialised healthcare units across 313 hospitals in 25 EU Member States, the ERNs can help improve public and professional awareness of rare diseases and complicated presentations of illness. These efforts have increased the likelihood of early, accurate diagnosis and effective treatment where available. Looking to the future, the ERNs could play an even greater role in supporting R&D, early diagnosis and access to treatment.

The potential of Big Data mining, bioinformatics and Digital Health platforms are already changing the healthcare landscape and hold tremendous potential. The ERNs could serve as a platform for trialling new approaches. One area for the ERNs to be further developed could be to assist in the collection of RWE and the establishment of registries to supplement the body of evidence generated by clinical trials. By acknowledging the unique challenges in developing an orphan product, the ERNs could play a role in both increasing the number of approved orphan products and shortening the time patients have to wait to access these treatments.