# Bridging pharmacodynamic biomarkers to clinical outcomes in pediatric inflammatory diseases

> **NIH NIH P50** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $816,558

## Abstract

Abstract:
Daily administration of high dose glucocorticoids is standard of care for the treatment of many
pediatric inflammatory diseases, including Duchenne Muscular Dystrophy (DMD) and Inflammatory
Bowel Disease (IBD). The side effect profiles of these potent drugs in children can be severe, with
stunting of growth, bone fragility, mood changes, and sleep disturbances among many others. It is
rare for glucocorticoids to be approved and labeled for pediatric disorders where they are routinely
being prescribed, despite these serious side effect profiles. Glucocorticoids were first approved for
use in adult disorders in the 1950s, yet progress on discovery and development of the next
generation drugs with significantly improved side effect profiles has been surprisingly slow. This has
been attributed to the complexity of mechanisms of actions of glucocorticoids (both with regards to
safety and efficacy), the growth in use of biologics for many pediatric diseases, and the lack of
interest from the pharmaceutical industry given the pervasive use and low cost of traditional
glucocorticoids. However, particularly in children, the decrease in quality of life and the increase in
clinical care ‘costs’ caused by side effects of glucocorticoids are substantial, but have been poorly
studied. This U54 RPDP application is from an established group with expertise in pediatric
pharmacology (inclusive of a newly funded NICHD T32 in clinical pediatric pharmacology), pediatric
drug development, and chronic inflammatory diseases in children. In this application, we focus on
pediatric inflammatory disorders, using two disease exemplars, DMD and IBD, as these may prove to
be great representatives of chronic pediatric diseases treated with glucocorticoids. The team at the
Children’s National Health System (CNHS) has partnered with an innovative venture philanthropy
company, ReveraGen BioPharma, to bridge pharmacodynamic biomarkers to clinical outcomes in the
pediatric population. In preliminary data presented in longitudinal studies of both IBD and DMD, we
describe validated panels of pharmacodynamic biomarkers for both multiple aspects of safety, as
well as anti-inflammatory efficacy. These pharmacodynamic safety and efficacy biomarkers are being
used to evaluate a promising next generation anti-inflammatory steroid (VBP15/vamorolone). The
goals of the proposed projects in this application are to bridge pharmacodynamic biomarkers to
clinical outcomes for specific safety and efficacy aspects of both glucocorticoids (prednisone) and
VBP15. This will set the stage for clinical trials of vamolorone and other anti-inflammatory drugs in
pediatric inflammatory diseases, where the data obtained is expected to enable more acute and
objective readouts of drug action in pediatric patients using well-characterized pharmacodynamic
biomarkers as outcome measures.

## Key facts

- **NIH application ID:** 9970230
- **Project number:** 5P50HD090254-05
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** JOHANNES NICOLAAS VAN DEN ANKER
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $816,558
- **Award type:** 5
- **Project period:** 2016-09-19 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970230

## Citation

> US National Institutes of Health, RePORTER application 9970230, Bridging pharmacodynamic biomarkers to clinical outcomes in pediatric inflammatory diseases (5P50HD090254-05). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/9970230. Licensed CC0.

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