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Published on: December 31, 2015
Population Pharmacokinetics of Nirsevimab in Preterm and Term Infants
Lindsay Clegg1, Ed Freshwater2, Amanda Leach3
1Clinical Pharmacology and Quantitative Pharmacology, R&D, AstraZeneca, Gaithersburg, MD, USA.
Insights
Nirsevimab effectively prevents respiratory syncytial virus (RSV) disease in infants. Weight-banded dosing is appropriate for all infants during their first RSV season, including those born prematurely or with underlying health conditions.
Area of Science:
- Pharmacokinetics and Drug Development
- Pediatric Infectious Diseases
- Immunology
Background:
- Nirsevimab, an extended half-life monoclonal antibody, is approved for RSV disease prevention in infants across North America and Europe.
- Understanding nirsevimab's pharmacokinetic (PK) profile is crucial for optimizing its use in diverse infant populations.
Purpose of the Study:
- To develop a population PK model for nirsevimab in preterm and term infants.
- To assess the impact of covariates like body weight and age on nirsevimab PK.
- To evaluate the appropriateness of weight-banded dosing strategies.
Main Methods:
- A 2-compartment PK model with first-order clearance and absorption was utilized.
- Data from 2683 participants across 5 clinical trials (8987 PK observations) were analyzed.
- Covariate analysis included body weight, postmenstrual age, race, second RSV season, and antidrug antibody status.
Main Results:
- Nirsevimab PK was characterized by a typical clearance of 3.4 mL/day in a 5 kg infant.
- Body weight and postmenstrual age were identified as primary covariates influencing clearance.
- Congenital heart disease (CHD) and chronic lung disease (CLD) did not significantly affect nirsevimab PK.
Conclusions:
- Weight-banded dosing (50 mg for <5 kg, 100 mg for ≥5 kg) is predicted to be appropriate for infants ≥1 kg in their first RSV season.
- These findings support the use of weight-banded nirsevimab dosing for all infants, including those with CHD, CLD, or born prematurely.
- The model successfully predicted PK in an independent cohort of healthy infants.
Abstract:
Nirsevimab, a monoclonal antibody with an extended half-life, is approved for the prevention of respiratory syncytial virus (RSV) disease in all infants in Canada, the EU, Great Britain, and the USA. A population pharmacokinetics (PK) model was built to describe the PK of nirsevimab in preterm and term infants, and to evaluate the influence of covariates, including body weight and age, in infants. Nirsevimab PK was characterized by a 2-compartment model with first-order clearance (CL) and first-order absorption following intramuscular (IM) administration. The typical CL in a 5 kg infant was 3.4 mL/day. Body weight and postmenstrual age were the primary covariates on CL, with minor effects for race, second RSV season, and antidrug antibody status (deemed not clinically relevant). Congenital heart disease (CHD) and chronic lung disease (CLD) did not significantly impact nirsevimab PK. The final population PK model, based on 8987 PK observations from 2683 participants across 5 clinical trials, successfully predicted PK in an additional cohort of 967 healthy infants. Weight-banded dosing (50 mg in infants <5 kg; 100 mg in infants ≥5 kg) was predicted to be appropriate for infants ≥1 kg in their first RSV season. Together, these data support weight-banded dosing of nirsevimab in all infants in their first RSV season, including in healthy infants, infants with CHD or CLD, and in infants born prematurely.
