Nirsevimab (1) – Beyfortus®

• Clinical trials
  • The MEDLEY trial is a completed double-blind RCT comparing nirsevimab with palivizumab in children during their first year of life and their first RSV season.
  • The D5290C00003 study is a completed, double-blind, randomised controlled trial comparing nirsevimab with placebo for the prevention of lower respiratory tract RSV infections.
  • The HARMONIE study is an ongoing, randomised, open-label, multicentre study investigating treatment with nirsevimab to prevent RSV-related hospitalisations compared with no intervention.

a) Children for whom there is an indication for secondary prophylaxis of lower respiratory tract infections caused by the respiratory syncytial virus (RSV) and for whom palivizumab is indicated

• The additional benefit is not proven.
• Overall, therefore, no additional benefit of nirsevimab has been proven in children with an indication for secondary prophylaxis of lower respiratory tract infections caused by RSV, for whom palivizumab is indicated, compared with the appropriate comparator therapy.
• mortality
  • For the endpoint of overall mortality, there was no statistically significant difference between the treatment groups at day 361.
• Morbidity – RSV-related lower respiratory tract infection
  • For the composite endpoint of RSV-associated lower respiratory tract infection, as well as for the individual components, no statistically significant difference was observed between the treatment groups at the analysis time points of Day 151 and Day 361.
  • The sub-component ‘RSV-related hospitalisation’ was defined as primary or nosocomial hospitalisation. A primary hospitalisation was defined as a hospital admission due to a respiratory infection of the upper or lower respiratory tract where the patient tested positive for RSV infection by reverse transcriptase-polymerase chain reaction (RT-PCR) within 2 days before or after admission.
  • The sub-component ‘RSV-related outpatient care’ comprises the number of children who required treatment at a hospital outpatient clinic, in acute care or at an accident and emergency department due to an RSV infection.
  • The operationalisation of both sub-components is appropriate. Therefore, the combined endpoint is used in its entirety for the benefit assessment.
• quality of life
  • Endpoints in the category of health-related quality of life were not collected in the MEDLEY study.
• Side effects
  • For the endpoints SUEs, severe AEs and discontinuation due to AEs, there was no statistically significant difference between the treatment groups at day 361.
• Overall assessment
  • For the endpoint of all-cause mortality, there was no statistically significant difference between the treatment groups at day 361. Similarly, in the morbidity category, there was no statistically significant difference between the treatment groups at the assessment time points of day 151 and day 361 for the combined endpoint of RSV-related lower respiratory tract infection. No data were provided for the category of health-related quality of life. In the category of side effects, there was also no statistically significant difference between the treatment groups.

b) Children with an indication for secondary prophylaxis against lower respiratory tract infections caused by the respiratory syncytial virus (RSV), for whom palivizumab is not indicated

• The additional benefit is not proven.
• There are therefore no suitable data available for assessing the additional benefit of nirsevimab compared with the appropriate comparator therapy in children with an indication for secondary prophylaxis of lower respiratory tract infections caused by RSV, in whom palivizumab is not indicated. An additional benefit is not proven.
• The patient populations presented from studies D5290C00003 and HARMONIE therefore do not, in each case, correspond to the specified patient population b).

Courtesy translation only, please refer to the German original.