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W-29: Analysis of Pediatric Investigation Plans and Post-Approval Pediatric Requirements of Monoclonal Antibodies for Asthma

Poster Presenter

Kristina Vishnevetskaya

Postdoctoral Fellow, Global Regulatory Affairs, GlaxoSmithKline
University of North Carolina
United States

Objectives

The objective of the literature review is to analyze the Pediatric Investigation Plans (PIPs), post-approval pediatric requirements, and pediatric clinical trials for monoclonal antibodies that are approved or currently in development for asthma.

ORAL PRESENTATION: 1:40PM

Method

The literature was reviewed to identify monoclonal antibodies for asthma in pediatric patients. A search was conducted on Drugs@FDA, the European Medicines Agency (EMA) website, and ClinicalTrials.gov for labels, approval letters, reviews, PIPs, and European Public Assessment Reports (EPARs).

Results

Seven monoclonal antibodies were identified as recently approved within the past 3 years or under development for pediatric asthma: benralizumab, reslizumab, mepolizumab, tralokinumab, dupilumab, lebrikizumab, and MEDI9929. Benralizumab, reslizumab, and mepolizumab have an approval in asthma while tralokinumab, dupilumab, lebrikizumab, and MEDI9929 are still in development. In the United States (US), benralizumab and mepolizumab both have an approved indication for severe asthma in patients 12 years and older. These products also have a deferral for this indication for patients 6 to 11 years old and a waiver for 0 to 5 years old. The adolescent subgroup (12-17 years of age) within the reslizumab Phase III adult and adolescent asthma studies was not granted a license in the US. Based on the reslizumab data in patients 12 to 17 years old, a waiver was granted for 0 to 11 years old. In the European Union (EU), benralizumab, mepolizumab, and reslizumab did not receive approval for the adolescent subgroup. Benralizumab has a deferral for patients 5 to 17 years of age and a waiver for 0 to 4 years of age. Mepolizumab and reslizumab received a deferral for 6 to 17 years old and a waiver for 0 to 5 years old. In the US, benralizumab has one post-marketing requirement (PMR) for asthma related to pharmacokinetics (PK) and pharmacodynamics (PD) in patients 6 to 11 years old. Mepolizumab has two PMRs in PK and PD for asthma in patients 6 to 11 years old, one of which is also a long term safety extension study. In the EU, the pediatric requirements for both approved products and those in development are published on EMA website. An evaluation of the PIP for these monoclonal antibodies revealed that the requirement ranged from 5 to 9 studies and there were a total of 48 PIP studies for all products combined. Within the total PIP studies, 54% were clinical efficacy and safety; 19% PK; 6% dose-ranging; 6% extrapolation, modeling, and simulation; and 4% non-clinical.

Conclusion

Monoclonal antibodies are being increasingly developed as therapeutic options for pediatric asthma in both the US and EU. Although only a few monoclonal antibodies are currently approved for asthma in various pediatric subgroups, there are more compounds still being studied. For the approved products, there appears to be differences in opinion between the FDA and EMA of what is required for a license in the adolescent population. Additionally, assessment of the PIPs demonstrates that the requirements for pediatric studies for each individual product are variable.