Nirsevimab safe, effective against RSV lower respiratory tract infection

A single dose of nirsevimab administered before or during the respiratory syncytial virus (RSV) season provides protection against RSV lower respiratory tract infection (LRTI) hospitalization and very severe infection in infants, according to the preliminary results of a clinical trial (HARMONIE) conducted in real-world settings.

The findings of HARMONIE were presented at the recent ESPID 2023 in Lisbon, Portugal. Lead author Simon Drysdale from University of London, London, UK, and his team conducted this study in the UK, France, and Germany to assess nirsevimab, a monoclonal antibody with an extended half-life that is licensed in the UK and European Union, for the prevention of hospitalization due to RSV-associated LRTI among infants.

RSV infections are a common cause of LRTIs in infants and may lead to substantial morbidity, according to Drysdale, noting that most RSV-related hospitalizations are among healthy infants born at term. Current preventive treatments are only available to a small proportion of infants.

Efficacy

In the study, a total of 8,058 infants (≥29 weeks gestational age) were randomized in an open label 1:1 ratio to receive a single intramuscular injection of nirsevimab (n=4,037; <5 kg 50 mg; ≥5 kg 100 mg) or no intervention (n=4,021; standard of care) before or during the RSV season.

Drysdale and his team monitored participants remotely for RSV LRTI hospitalization, defined as treating physician decision to admit to inpatient care without confirmed RSV, and/or very severe RSV LRTI, defined as SpO2 <90 percent and oxygen supplementation, following a single physical visit. Adverse events (AEs) were monitored for 1 year.

Of the patients, 3,916 (48.6 percent) were ≤3.0 months, 1,912 (23.7 percent) were >3.0 and ≤6.0 months, and 2,230 (27.7 percent) were >6.0 months of age. The efficacy of nirsevimab was 83.21 percent (95 percent confidence interval [CI], 67.77‒92.04) against hospitalization due to RSV LRTI and 75.71 percent (95 percent CI, 32.75‒92.91) against very severe RSV LRTI. [ESPID 2023, abstract O0082]

"HARMONIE has demonstrated the significant impact of nirsevimab on RSV LRTI, implemented in close to real life situations, in all infant cohort," said Drysdale. "Consistent with data from the pivotal trials, the safety profile of nirsevimab in HARMONIE was favourable with no apparent safety concerns."

Safety

Another study presented at ESPID 2023 assessed the safety profile of nirsevimab in healthy infants who received the authorized dose of the drug prior to their first RSV season and found it acceptable through 360 days postdose.

Of the 3,854 participants included, 2,570 received nirsevimab and 1,284 placebo. AE incidence was comparable between the two treatment groups. Most AEs were mild or moderate in severity, with some deemed to be related to treatment.

The incidence of AEs of special interest was low, occurring in only six (0.2 percent) nirsevimab recipients. Mortality rates were similar between treatment groups (0.2 percent; three placebo and six nirsevimab recipients). None of the deaths were considered treatment-related. [ESPID 2023, abstract PD0122]

This study pooled data from two double-blind, randomized trials: phase IIb (infants ≥29 to <35 weeks gestational age) and phase III MELODY (infants ≥35 weeks gestational age). The investigators, led by Vaishali Mankad, AstraZeneca, Vaccines and Immune Therapies, Biopharmaceuticals R&D, Durham, US, assessed all treatment-emergent AEs through 360 days postdose (5 nirsevimab half-lives).

Specific theoretical risks of monoclonal antibody treatment, such as immediate hypersensitivity, immune complex disease, and thrombocytopenia (previously associated with palivizumab) were defined as AEs of special interest.