75% of rare (orphan) diseases are known to affect children, and a vast majority of these diseases are without any approved therapeutic option with the consequence of significant off-label use of medicines. The global clinical development of medicines for orphan diseases in pediatric patients is challenging for drug developers as different regulatory requirements were established in the EU and US for pediatric investigation plans (PIP) and pediatric study plans (PSP) for new products. In the EU, PIPs are mandatory for orphan drugs, often including a clinical development program, while in the US in the past, orphan drugs were exempted from PSP evaluation. However, it was acknowledged that new approaches are needed to accelerate development of safe and effective new drugs particularly for pediatric oncological diseases. A new FDA Guidance for Industry was established in 2019, eliminating the orphan exemption for pediatric studies for cancer drugs directed at relevant molecular targets. The overall goal of molecularly targeted pediatric cancer investigation is to provide clinically meaningful study data on safety and preliminary efficacy to achieve a pediatric labelling. The major challenge is how to generate clinical data for orphan drugs in pediatric populations.
Key learnings:
- Regulatory requirements for PIPs and special incentives for orphan
drug development in the EU
- Revision of class waivers and chances for more orphan drugs for children
- New requirements for PSPs for orphan drugs considering the molecular
target list from the FDA
- Possibilities for evidence-generation outside of randomized, controlled trials for pediatric orphan drug development
