Don’t forget the rare but collectively common diseases

A rare disease is defined by having a particularly low prevalence and incidence. For drugs used to treat rare diseases, there are regulatory requirements to obtain orphan designation, a status that triggers certain regulatory and market advantages.

The requirements for obtaining orphan drug designation vary in different countries and regions. In the EU, it is a prerequisite that the rare disease the drug is intended to treat, prevent, or diagnose has a prevalence of no more than 5 out of 10,000 people, while in the USA, it is a prevalence of no more than 200,000 people out of the country’s population.

Some rare diseases are extremely rare, such as ribose-5-phosphate isomerase deficiency, of which there are only a few documented cases worldwide. In comparison, the prevalence in Europe for newborns with cystic fibrosis, another, albeit less rare disease, is approximately 1 in 5,000.

When there are so few individuals suffering from a specific rare disease, one might not immediately think that rare diseases constitute a significant disease burden and a societal healthcare challenge. However, the picture is more nuanced than that.

Many complicating factors need to be considered, and new initiatives are needed to keep the focus on rare diseases so they are not overlooked amidst other current healthcare issues.

It is estimated that there are between 5,000 and 8,000 different rare diseases, together affecting 6-8% of the total population.

Although the total number of individuals with a rare disease is significant (between 27 and 36 million in the EU), most healthcare professionals’ general knowledge and experience with each specific rare disease and its consequences are often limited. Many patients undergo prolonged and complicated diagnostic processes, with the risk of misdiagnosis and potentially harmful treatment regimens.

While rare diseases may not necessarily be severe, they are often progressive, associated with moderate or severe symptoms, and have a significant negative impact on quality of life and life expectancy.

Most rare diseases cannot be cured, and effective treatment options are generally lacking. It is estimated that only about 5% of rare diseases have an approved treatment. Additionally, approximately half of all rare diseases are congenital or begin in childhood.

The combination of these factors results in significant uncertainty and social burden for patients and their families, impacting education, employment, and productivity.

It is challenging to estimate the direct and indirect socio-economic consequences of rare diseases, as rare diseases encompass a highly heterogeneous group of disorders for which there is inadequate epidemiological data.

Therefore, traditional methods for analyzing cost-effectiveness and benefit may not necessarily be applicable to the evaluation of new and existing treatments.

Comparing costs per patient without considering prevalence can have a more substantial impact on society when treating rare diseases compared to treating non-rare diseases, as rare diseases often involve younger individuals and are more severe.

This is why it is important to ensure that we provide equal quality in healthcare and services for individuals with rare diseases, not only because of principles of equality but also because there are significant gains to be made for patients, families, and society through prompt and accurate diagnosis, effective treatment, shorter and less resource-intensive diagnostic pathways, maintained employment and productivity, improved quality of life, and extended life expectancy.

What areas could be relevant to focus on in order to promote care and support for individuals with rare diseases?

Improving the regulatory framework and promoting research and development in personalized medicine and diagnostics, for example, through increased use of gene sequencing, could reduce the time for diagnosis and the risk of overlooked or misdiagnosed rare diseases.

Similarly, enhancing the training of healthcare professionals and increasing awareness about the existence and implications of rare diseases is crucial.

It is also important to maintain existing regulatory advantages and market exclusivity associated with orphan drug designation. Further push and pull incentives to promote research into innovative and more effective treatment options, including the use of cell and gene therapies, would also be relevant initiatives.

Facilitating the development of new orphan drugs by introducing innovative methodologies and designs for clinical trials involving small patient groups, making it less time-consuming and costly to conduct development activities, is another potential avenue for improvement.

From a Danish perspective, it would be especially relevant to consider the care of rare diseases in the future organization of the healthcare system, as a structure commission, set to be established soon, will outline and provide recommendations for in the spring of 2024.