Nirsevimab 100mg/1ml solution for injection pre-filled syringes

A systematic review with a meta-analysis was performed to gather available evidence on the effectiveness of monoclonal antibody nirsevimab in the prevention of lower respiratory tract diseases (LRTDs) due to respiratory syncytial virus (RSV) in children and newborns (CRD42024540669). Studies reporting on real-world experience and randomized controlled trials (RCTs) were searched for in three databases (PubMed, Embase, and Scopus) until 1 May 2024. Our analysis included five RCTs, seven real-world reports, and one official report from the health authorities. Due to the cross-reporting of RCTs and the inclusion of multiple series in a single study, the meta-analysis was performed on 45,238 infants from 19 series. The meta-analysis documented a pooled immunization efficacy of 88.40% (95% confidence interval (95% CI) from 84.70 to 91.21) on the occurrence of hospital admission due to RSV, with moderate heterogeneity (I2 24.3%, 95% CI 0.0 to 56.6). Immunization efficacy decreased with the overall length of the observation time (Spearman’s r = −0.546, p = 0.016), and the risk of breakthrough infections was substantially greater in studies with observation times ≥150 days compared to studies lasting <150 days (risk ratio 2.170, 95% CI 1.860 to 2.532). However, the effect of observation time in meta-regression analysis was conflicting (β = 0.001, 95% CI −0.001 to 0.002; p = 0.092). In conclusion, the delivery of nirsevimab was quite effective in preventing hospital admissions due to LRTDs. However, further analyses of the whole RSV season are required before tailoring specific public health interventions.

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Background: In clinical trials, recently introduced respiratory syncytial virus (RSV) immunisation products have shown high efficacy in preventing severe RSV outcomes. Implementing successful immunisation programmes is however key to realising these benefits in real-world settings. We aimed to investigate uptake of the long-acting monoclonal antibody nirsevimab, the RSV maternal vaccine, and RSV vaccines for older adults in countries where immunisation programmes have been introduced, and to explore how uptake varies between countries and population subgroups. Methods: In this systematic review and meta-analysis, we carried out four monthly searches in Medline, Embase, and Global Health databases for studies reporting uptake of nirsevimab, the RSV maternal vaccine, and RSV vaccines for older adults. We included population-based studies published between December 1, 2022 and February 5, 2025. Two independent reviewers screened studies, extracted data, and completed a risk of bias assessment using the Joanna Briggs Institute (JBI) Critical Appraisal Tools. We assessed uptake stratified by country and socio-demographic and clinical subgroups. Meta-analyses were conducted using random-effects modelling. PROSPERO registration number: CRD42025643585. Findings: We screened a total of 1267 studies, 43 of which met the inclusion criteria reporting data on over 1.38 million individuals from six countries. Nirsevimab uptake data were reported in 34 studies: 16 from Spain, eight from the United States, seven from France, one with combined data from Andorra and Spain, and one from each of Italy and Luxembourg. Our pooled estimates showed that nirsevimab uptake on population level was 90.1% (95% confidence interval (CI): 86.4-92.9) in Spain and 51.2% (95% CI: 29.3-72.7) in the United States during the 2023/24 RSV season. Uptake data for the RSV maternal vaccine and RSV vaccines for older adults were reported in five and eight studies, respectively, all from the United States. Meta-analysis showed population-level uptake of 30.5% (95% CI: 20.6-42.6) and 18.2% (95% CI: 10.8-28.9), respectively. Uptake varied across subgroups. Interpretation: Uptake of nirsevimab varied substantially between the countries that have implemented infant RSV immunisation programmes. Despite the limited number of studies and the lack of more accurate data at national level the low uptake estimates for RSV maternal vaccine and RSV vaccines for older adults are concerning. National, clinical, and public health initiatives are needed to increase uptake of RSV immunisation products and ensure maximum benefit to people currently at risk of severe RSV outcomes. Funding: Health Data Research UK, Inflammation and Immunity Driver Programme.

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Background: Respiratory Syncytial Virus (RSV) is one of the primary pathogen responsible for severe lower respiratory tract infections in preterm infants, placing a significant burden on patients, their families, and society. Nirsevimab, a recently developed RSV monoclonal antibody, has demonstrated promising efficacy in this population according to preliminary studies. However, there remains a need for comprehensive systematic reviews and meta-analyses to evaluate the effectiveness of nirsevimab in preventing RSV-related lower respiratory tract infections in preterm infants. Methods: A search of the PubMed and EMBASE databases was conducted to identify randomized controlled trials (RCTs) and observational studies assessing the prevention of RSV infection in preterm infants using nirsevimab. Relevant data were extracted and subjected to meta-analysis. Results: Five studies involving a total of 7,347 preterm infants (3,987 in the nirsevimab group and 3,360 in the control group) were included. The meta-analysis revealed that nirsevimab significantly reduced the incidence of medically attended RSV-associated lower respiratory tract infections (OR = 0.25; 95% CI: 0.15, 0.40; P < 0.0001) and hospitalizations due to RSV-associated lower respiratory tract infections (OR = 0.27; 95% CI: 0.19, 0.38; P < 0.0001). Conclusion: Nirsevimab significantly decreases the risk of RSV-related infection in preterm infants and represents a valuable intervention for RSV prevention in this vulnerable population. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42025629937.

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BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. METHODS: HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. FINDINGS: Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the standard care group (n=4019). The median age at randomisation was 4·00 months (IQR 1·0-7·0; range 0·0-12·0, and 4195 (52·1%) were male and 3862 (47·9%) were female. Up to 180 days, 12 (0·3%) of 4038 infants in the nirsevimab group and 68 (1·7%) of 4019 infants in the standard care group had been hospitalised for RSV-associated lower respiratory tract infection, corresponding to a nirsevimab efficacy of 82·7% (95% CI 67·8-91·5; p<0·0001). Most participants experienced grade 1 (2759 [68·7%] of 4016 in the nirsevimab group; 2696 [67·1%] of 4018 in the standard care group) or grade 2 (1447 [36·0%] of 4016 in the nirsevimab group; 1436 [35·7%] of 4018 in the standard care group) treatment-emergent adverse events, and no apparent safety concerns were raised up to 365 days after dosing. INTERPRETATION: Nirsevimab offers consistent and sustained protection against hospitalisation due to RSV-associated lower respiratory tract infection for at least 6 months. This finding provides global health systems greater flexibility when implementing nirsevimab, providing substantial benefit in the ongoing effort to reduce the burden of infant RSV and the potential wider public health value. FUNDING: Sanofi and AstraZeneca.

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