Nirsevimab (3) – Beyfortus®

• Clinical trials
  • The HARMONIE trial is an ongoing, open-label, randomised, multicentre trial comparing nirsevimab with no treatment for the prevention of lower respiratory tract RSV infections in children during their first RSV season.
  • The MELODY trial is a completed double-blind RCT comparing nirsevimab with placebo for the prevention of lower respiratory tract RSV infections in children.

Children during their first RSV season, for the prevention of lower respiratory tract infections caused by respiratory syncytial virus (RSV), which are not covered by the therapeutic indication for RSV antibodies

• Overall, for nirsevimab in children during their first RSV season, for the prevention of lower respiratory tract RSV disease not covered by the therapeutic indications for RSV antibodies, there is an indication of a considerable additional benefit compared with a ‘wait-and-see’ approach.
• The potential for bias in the results of the patient-relevant endpoints from the HARMONIE study is assessed as low, with the exception of the endpoint ‘discontinuation due to adverse events’.
• Furthermore, in both the HARMONIE and MELODY studies, there are uncertainties regarding the proportion of children included who do not correspond to the target population for the therapeutic indication being assessed here. These uncertainties limit the certainty of the study results.
• However, a meta-analytical synthesis of the results from the HARMONIE and MELODY studies – taking into account the uncertainties outlined – provides an indication that there is additional benefit based on the strength of the evidence.
• mortality
  • Only in the MELODY study were four deaths recorded in the intervention arm. No statistically significant difference was observed between the treatment groups.
• Morbidity – RSV-related lower respiratory tract infection
  • The composite endpoint of RSV-related lower respiratory tract infection was assessed only in the MELODY study. The endpoint comprises the components RSV-related hospitalisation and RSV-related outpatient care.
  • For the combined endpoint of RSV-associated lower respiratory tract infection, the analysis at day 361 and day 151 each showed a statistically significant advantage for nirsevimab compared with a ‘wait-and-see’ approach.
  • However, an effect modification with respect to age was observed: for children aged ≤ 6 months, there was a statistically significant advantage of nirsevimab compared with a ‘wait-and-see’ approach, whereas this was not the case for children aged > 6 months.
• Morbidity – Severe RSV-associated lower respiratory tract infection
  • The endpoint ‘severe RSV-associated lower respiratory tract infection’ is defined as hospitalisation due to an RSV-associated lower respiratory tract infection.
  • For the endpoint of severe RSV-associated lower respiratory tract infection, the meta-analysis shows a statistically significant advantage for nirsevimab compared with a ‘wait-and-see’ approach, both in the analyses at days 361 and 366 and at day 151.
• Overall view
  • In the overall review of the results, nirsevimab appears to be effective in children during their first RSV season for the prevention of respiratory syncytial virus (RSV)-related lower respiratory tract diseases—which are not addressed in the therapeutic guidance on RSV antibodies—an added benefit can be inferred based on the positive effects observed in the morbidity endpoints, namely RSV-related lower respiratory tract infection and severe RSV-related lower respiratory tract infection – an additional benefit can be inferred, the extent of which is classified as considerable.

Courtesy translation only, please refer to the German original.