Model-Informed Approach Supporting Approval of Adalimumab (HUMIRA) in Pediatric Patients with Ulcerative Colitis from...

Area of Science:

• Pharmacology
• Pediatric Gastroenterology
• Drug Development

Background:

• Adalimumab is approved for various conditions in adults and children.
• Ulcerative colitis (UC) treatment in pediatric patients requires specific efficacy and safety evaluations.
• The U.S. Food and Drug Administration (FDA) oversees drug approvals and label expansions.

Purpose of the Study:

• To report the FDA approval of adalimumab for pediatric patients with moderate to severe ulcerative colitis (UC).
• To describe the model-informed drug development (MIDD) approach used to support the expanded indication.
• To highlight the use of modeling and simulation in drug development for pediatric populations.

Main Methods:

• A multicenter, randomized, double-blind trial (Study PUC-I) evaluated adalimumab effectiveness in 93 pediatric patients (5-17 years).
• Model-informed exposure bridging strategy was employed, integrating efficacy and safety data.
• Dosing regimen adjustments were made from the trial's mg/kg basis to tiered, fixed doses, including maintenance options.

Main Results:

• FDA approved an efficacy supplement for adalimumab injection on February 24, 2021, for pediatric UC patients aged 5 and older.
• The approved dosing regimen differs from the trial regimen, incorporating model-based adjustments for safety and efficacy.
• No significant exposure-safety relationship issues were identified in prior pediatric studies with adalimumab.

Conclusions:

• Model-informed drug development successfully supported the expanded indication of adalimumab for pediatric UC.
• MIDD facilitated the approval despite a limited clinical trial size by leveraging modeling and simulation.
• This case exemplifies the utility of MIDD in pediatric drug development and regulatory approvals.