Nirsevimab 50mg/0.5ml solution for injection pre-filled syringes

Background Respiratory syncytial virus (RSV) is a leading cause of morbidity and mortality among infants with a global incidence of 9.5% and a mortality rate of 2.2%. The management of RSV infection is mainly supportive and, aside from emerging monoclonal antibodies, there has been no benefit of most preventive measures. Recent evidence suggests the potential of nirsevimab in preventing RSV infection. Objective This study aims to determine the efficacy and safety of nirsevimab in preventing RSV infection among infants using a review of relevant clinical trials. Methods We performed a random-effects meta-analysis among infants comparing nirsevimab injection vs. placebo. MEDLINE, CENTRAL, Scopus, and ClinicalTrials.gov were searched for relevant trials from inception to June 2022. The selected studies were assessed for risk of bias using the Revised Cochrane Risk-of-Bias (RoB2) tool and for quality of evidence using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results Two studies were included. Data analysis showed that among infants, nirsevimab given before the RSV season significantly reduced the risk of medically attended RSV-related infection (RR: 0.26; 95% CI: 0.18–0.38) and the risk of hospitalization due to RSV infection (RR: 0.24; 95% CI: 0.13–0.47). There was no difference in terms of adverse events leading to death (RR: 0.78, 95% CI: 0.20–2.98) and adverse events of special interest (RR: 0.92, 95% CI: 0.25–3.38). Conclusions The use of nirsevimab to prevent RSV infections and hospitalization shows its promising potential, but studies on its cost-effectiveness are lacking. We recommend that further studies be done to look into the applicability and cost-effectiveness of nirsevimab.

Abstract licence: CC BY 4.0

Abstract Nirsevimab is a monoclonal antibody that binds to the respiratory syncytial virus (RSV) fusion protein. During the Phase 2b (NCT02878330) and MELODY (NCT03979313) clinical trials, infants received one dose of nirsevimab or placebo before their first RSV season. In this pre-specified analysis, isolates from RSV infections were subtyped, sequenced and analyzed for nirsevimab binding site substitutions; subsequently, recombinant RSVs were engineered for microneutralization susceptibility testing. Here we show that the frequency of infections caused by subtypes A and B is similar across and within the two trials. In addition, RSV A had one and RSV B had 10 fusion protein substitutions occurring at >5% frequency. Notably, RSV B binding site substitutions were rare, except for the highly prevalent I206M:Q209R, which increases nirsevimab susceptibility; RSV B isolates from two participants had binding site substitutions that reduce nirsevimab susceptibility. Overall, >99% of isolates from the Phase 2b and MELODY trials retained susceptibility to nirsevimab.

Abstract licence: CC BY 4.0