European regulators have moved a step closer to approving Enflonsia (clesrovimab; Merck Sharp & Dohme) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season. 

RSV is a highly prevalent seasonal respiratory virus and a leading cause of infant hospitalizations globally, placing a substantial burden on healthcare systems. In the European Union, Norway, and the UK, RSV is estimated to cause around 250,000 hospitalizations annually in children under 5 years. 

Enflonsia is designed to provide passive immunity during a baby’s first RSV season, when risk of severe disease is highest. Clesrovimab, Enflonsia’s active substance, is a fully human IgG1κ neutralizing monoclonal antibody. It incorporates three amino acid substitutions in the Fc region to improve binding to the neonatal Fc receptor, thereby extending its half-life. By targeting the RSV fusion protein on the viral envelope, clesrovimab prevents viral attachment and entry into host cells.

In the phase 2b/3 CLEVER trial, involving 3614 infants given a single 105 mg intramuscular dose of clesrovimab, the incidence of medically-attended RSV lower respiratory tract infections fell by approximately 60.4% over 150 days compared with placebo, and RSV-related hospitalizations were reduced by about 84.2%. Safety profiles were comparable, with serious adverse events reported in 11.5% of clesrovimab-treated infants versus 12.4% in the placebo group.

The SMART trial is a phase 3 study comparing clesrovimab with palivizumab in infants and children at increased risk for severe RSV disease. It serves to confirm the tolerability and efficacy signal seen in CLEVER.

If the positive opinion given to Enflonsia by the European Medicines Agency (EMA) is approved by the European Commission, it will be supplied as a 105 mg solution for injection in prefilled syringes and administered as a single fixed dose regardless of infant weight. One dose provides passive immunity for up to 5 months — covering the duration of a typical RSV season in Europe, which usually runs from autumn through spring. The most common side effects are injection-site pain, erythema, swelling, and rash.

Detailed recommendations for Enflonsia use will be described in the summary of product characteristics, which will be published on the EMA website after the European Commission grants marketing authorization.