Amanda Leach (United States of America)
AstraZeneca -Author Of 2 Presentations
POOLED EFFICACY OF NIRSEVIMAB AGAINST RSV LOWER RESPIRATORY TRACT INFECTION IN PRETERM AND TERM INFANTS
Abstract
Backgrounds:
Nirsevimab reduced medically attended (MA) respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) incidence in two double-blind, placebo-controlled studies (Phase IIb [NCT02878330]: healthy very and moderately preterm infants ≥29 to <35 weeks gestational age [wkGA], efficacy 70.1%; Phase III: MELODY [NCT03979313], healthy term and late preterm infants ≥35 wkGA, efficacy 74.5%). We report a pooled efficacy analysis of nirsevimab in term and preterm infants ≥29 wkGA through Day 151.
Methods
Infants were randomised 2:1 to receive either an intramuscular injection of nirsevimab (<5 kg, 50 mg; ≥5 kg, 100 mg) or placebo, before their first RSV season. Data were pooled from the Phase IIb and MELODY studies for those infants under the optimised dosing regimen (i.e., infants <5 kg at dosing and receiving the 50 mg dose from Phase IIb and all infants in MELODY) to evaluate efficacy (relative risk reduction versus placebo) against varying severities of MA RSV LRTI.
Results:
Overall, 860 infants from Phase IIb (median age at randomisation: 1.60 [range 0.1–6.4] months; female: 47.6%) and 1490 infants from MELODY (median age at randomisation: 2.60 [0.03–11.10] months; female: 48.4%) were included. Demographics were comparable across studies, except for GA and age at randomisation. Nirsevimab had an efficacy of 79.5% against MA RSV LRTI, 77.3% against RSV LRTI hospitalisation and 86.0% against very severe RSV LRTI through Day 151 (Figure). Consistent efficacy was observed across subgroups defined by age at randomisation, sex, ancestry, weight or geographical region and across endpoints of differing disease severity.
Conclusions/Learning Points:
In a pooled analysis of two randomised, placebo-controlled studies, prophylaxis with nirsevimab demonstrated consistent efficacy across severities of RSV LRTI through Day 151.
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.
