Orphan drugs & paediatric medicines: how to deliver for children with rare diseases (Guest blog)

There is some overlap between paediatric medicines development and research on medicines for rare diseases, so-called “orphan medicines”. Rare diseases are typically diagnosed during childhood. In fact, around 75% of rare diseases are known to affect children, and around 3 in 10 of these young people die before their 5th  birthday.

All medicine research and development is costly, complex and uncertain, but researchers working on paediatric and orphan medicines face unique challenges. In paediatric medicines, there are additional complexities arising from conducting trials with patients who are still growing and developing; additional ethical issues also arise when recruiting young patients and securing their assent and informed consent from their parents.

In rare disease research, the challenges are obvious: clinical trial recruitment is hampered by the low number of patients and, even if a product is eventually approved, the potential patient population for any successful therapy is small.

Yet, there is a clear medical need for new treatments that have been trialled in children, and for orphan medicines targeting the estimated 5,000 rare diseases that have been characterized and are known today. That is why policymakers have crafted targeted incentives designed to support research and development in these crucial areas and mitigate some of the challenges present in paediatric and rare disease drug development.

Incentivising medicine development
In 1999, European Union policymakers unveiled a number of incentives for the development of rare disease therapies. They created the Committee for Orphan Medicinal Products (COMP) at the European Medicines Agency (EMA) and offered market exclusivity for orphan designated products that are ultimately authorised.

Separately, in 2006, the Paediatric Regulation created new obligations on medicines developers to investigate their products in children. It established the Paediatric Committee (PDCO) at the EMA setting out new procedures, incentives and rewards, and requirements for authorisation – including the development of a Paediatric Investigation Plan (PIP).

What I am interested in is the interaction between these two Regulations and how they support the development of new therapeutic options for children with rare diseases. This is explored in depth in a recently-published article written in collaboration with colleagues from some of the other pharmaceutical companies active in this space. We wanted to see whether the current framework has delivered for the millions of children in Europe living with a rare disease for which there is no treatment.

So, how did it go? In broad terms, both Regulations should be considered a success in terms of improving the pipeline of orphan paediatric medicines.

There has been a significant increase in the number of orphan designated products intended for children only, for adults only, or for both children and adults. However, as with any medicine development programmes, attrition rates are high. Of the orphan products that made it to market, most were for adults only, with a smaller number suitable for both children and adults, and only 6% of orphan products were authorised for paediatric use only.

The Paediatric Regulation also plays a part in stimulating research in rare paediatrics diseases.  However, more remains to be done to ensure that more treatments are approved for children with rare diseases.

Doing better
Undoubtedly there are children living with rare diseases who now have treatment options that simply would not exist if not for the package of measures introduced through the Orphan and Paediatric Regulations. Having said that, we have identified concrete actions that could make the system work even better within the existing regulatory framework, which has proven its value in promoting research and development of orphan and paediatric medicines.

These include better coordination between the COMP and PDCO; greater recognition of modelling and simulation methods; and wider acceptance of alternative and innovative clinical trial design. (For more details, see our paper in Clinical Therapeutics, November 2019).

Both the Orphan and Paediatric Medicines Regulations have successfully stimulated the development of medicines for special populations. While there are areas of overlap between orphans and paediatrics, such as the limited number of patients affected by the disease that create challenges to conducting research, the two Regulations are separate instruments that work in different ways. Upholding a stable, favourable and predictable regulatory environment is needed to achieve continued progress in the fields of paediatric and orphan medicines. 

Thomas Kühler

Head Global Regulatory Science & Policy EU/AMEE
Global Regulatory Affairs - Global Regulatory Science &...
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