Leveraging Adult Efficacy Data for Pediatrics Using Bridging Biomarkers

Presentation Title: Clinical Translational Science: Leveraging Adult Efficacy Data for Pediatrics using Bridging Biomarkers

Session 4: Beyond Surrogate Endpoints: Other Ways Translational Science Can Support Drug Development

Speaker: Christine Garnett, PharmD

Summary:

For conditions that affect pediatric and adult populations, there may be effective medications or other interventions that are approved for adult populations but have not been studied in traditional clinical trials with pediatric populations due to ethical and logistical limitations. Bridging biomarkers present an opportunity to build on an existing approved medication to evaluate effectiveness in a pediatric population using a smaller, more efficient clinical trial than a traditional clinical endpoint would allow. This case study presented the successful use of pulmonary vascular resistance as a bridging biomarker to extrapolate efficacy of a drug, Bosentan, from adults to pediatric patients with pulmonary arterial hypertension, resulting in approval in pediatric populations.

Key Takeaways:

• Establishing a bridging biomarker must satisfy the 5 core criteria
1. Disease must be similar in pediatric and adult populations
2. In adults, drug must be safe and effective, and have an effect on clinical outcome and proposed biomarker
3. Biomarker must capture principal causal pathway
4. Drug must not have negative effects not captured by biomarker
5. In adults, clinical effects must be somewhat proportional to biomarker effects
• Pediatric extrapolation using bridging biomarkers has been an important process for drug approvals, especially given ethical and logistic challenges in running clinical trials in children