Michael E. Abram (United States of America)
AstraZeneca -Author Of 1 Presentation
NIRSEVIMAB FOR THE PREVENTION OF RESPIRATORY SYNCYTIAL VIRUS INFECTION: NEUTRALISING ANTIBODY LEVELS FOLLOWING A SINGLE DOSE
Abstract
Backgrounds:
Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI) and hospitalisation in infants. In two global, pivotal, placebo-controlled studies, nirsevimab, a monoclonal antibody to the RSV fusion protein with extended half-life, reduced medically attended RSV LRTI versus placebo throughout the RSV season (Phase III NCT03979313: MELODY, healthy term and late preterm infants, 74.5%; Phase IIb NCT02878330: healthy preterm infants, 70.1%). We measured RSV neutralising antibodies (Nab) from these studies through Day 361.
Methods
Infants were randomised 2:1 to receive one intramuscular injection of nirsevimab or placebo, before their first RSV season. Serum samples collected pre- and post-dose were tested in a validated RSV neutralisation assay; RSV Nab levels are reported in international units (IU)/mL.
Results:
Overall, 1402 infants from MELODY and 741 infants from Phase IIb had available data. Baseline geometric mean RSV Nab levels were similar in both studies (MELODY, 134 IU/mL; Phase IIb, 87 IU/mL). At Day 151, nirsevimab recipients exhibited RSV Nab levels approximately 50-fold higher (MELODY, 6901 IU/mL; Phase IIb, 4799 IU/mL) versus baseline, with highest levels sampled at Day 31 in MELODY (19,711 IU/mL; Figure) and at Day 91 in Phase IIb (8479 IU/mL); levels remained >7-fold higher through Day 361 (MELODY, 978 IU/mL; Phase IIb, 739 IU/mL). At Day 361, placebo recipients with no confirmed RSV infection during the studies had RSV Nab levels of 38–48 IU/mL; nirsevimab recipients had RSV Nab levels of 757–982 IU/mL, >19-fold higher than placebo recipients without confirmed RSV infection.
Conclusions/Learning Points:
Following immunisation with nirsevimab, RSV Nab levels at Day 151 were approximately 50-fold higher than baseline. RSV Nab levels remained high through Day 361, suggesting protection beyond Day 151.
