Drug development in dermatology: challenges in treating young patients

Area of Science:

• Dermatology
• Pediatric Drug Development
• Regulatory Science

Background:

• Children are often 'therapeutic orphans' in drug development, necessitating specific pediatric requirements from regulatory bodies like the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
• The EMA mandates a 'pediatric investigation plan' (PIP) early in the drug development process.
• Skin maturation differs between age groups, impacting drug absorption and efficacy, yet regulatory approaches vary significantly between the US and EU.

Purpose of the Study:

• To analyze the differing pediatric drug development requirements between the FDA and EMA.
• To highlight the challenges posed by the EMA's stringent PIP process.
• To discuss the implications of these regulatory differences on the pace of pediatric drug development.

Main Methods:

• Comparative analysis of FDA and EMA pediatric drug development guidelines.
• Case study examples of crisaborole for atopic dermatitis and psoriasis drug development.
• Review of the impact of PIP negotiations on development timelines and strategies.

Main Results:

• The FDA accepted pivotal trials for crisaborole (atopic dermatitis) across a wide age range (2-79 years), which the EMA also accepted as part of its PIP.
• For psoriasis, the EMA's PIP specifically requires separate efficacy and safety data in children aged 6-17 years.
• EMA's rigid stance and lengthy PIP negotiations contrast with the FDA's more flexible approach, leading to frustration and delays.

Conclusions:

• Regulatory divergence between the FDA and EMA creates significant challenges for pediatric drug development, particularly for skin disorders.
• The EMA's stringent requirements, while aiming for safety, can hinder timely access to new treatments for pediatric populations.
• Pharmaceutical companies need a deep understanding of regulatory nuances, patience, and potentially external expertise to navigate these complex processes effectively.