Challenges and considerations for development of therapeutic proteins in pediatric patients

Area of Science:

• Pharmacology
• Pediatric Drug Development
• Biologics

Background:

• Therapeutic proteins (TPs) offer promising treatments for pediatric patients due to their specificity and tolerability.
• However, understanding the ontogeny of TP pharmacokinetics (PK) and disposition in children remains limited.
• The development of TPs for pediatric use is an evolving field with unique scientific and regulatory considerations.

Purpose of the Study:

• To review the current landscape of TP development for pediatric use, focusing on monoclonal antibodies and fusion proteins.
• To evaluate dose-selection strategies for pediatric studies, particularly the adequacy of relying solely on adult PK data.
• To propose a framework for optimizing clinical pharmacology strategies in pediatric TP development.

Main Methods:

• Review of TPs approved for pediatric use, with an emphasis on monoclonal antibodies and fusion proteins.
• Analysis of dose-selection strategies employed in pivotal pediatric studies.
• Examination of pharmacokinetic properties and their implications for pediatric dosing.

Main Results:

• Dose selection for pediatric studies often relies exclusively on adult PK data, which may be insufficient for complex PK profiles.
• Body weight-based scaling from adult doses can result in under-exposure in younger pediatric patients.
• Tiered-fixed dosing strategies show potential for achieving comparable TP exposure across a wide pediatric age range.

Conclusions:

• Pediatric drug development for TPs necessitates specialized approaches beyond simple adult dose scaling.
• Pharmacometrics should be integrated into pediatric TP development due to population uniqueness and study challenges.
• A distinct framework is proposed to guide clinical pharmacology strategies for pediatric TP development.