Merck's RSV Antibody Enflonsia Approved in EU; Researchers Develop Antibody Cocktail Against RSV and hMPV

Merck's Enflonsia (clesrovimab) has been approved by the European Commission for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants during their first RSV season. Separately, researchers in China have published a study in Science Translational Medicine describing a new antibody cocktail for protection against RSV and human metapneumovirus (hMPV), identified from immune cells of pediatricians.

The long-acting monoclonal antibody Enflonsia is designed to provide protection for up to five months with a single dose and does not require weight-based dosing. The approval applies across all 27 EU states, as well as Iceland, Liechtenstein and Norway, with availability in member countries dependent on completion of reimbursement procedures. RSV is a common seasonal virus that can lead to serious respiratory conditions, including bronchiolitis and pneumonia, and remains a leading cause of hospitalisation among infants worldwide.

The European decision is supported by results from the phase 2b/3 CLEVER trial and interim data from the phase 3 SMART trial, which assessed the safety and efficacy of Enflonsia in infants entering their first RSV season, including those at increased risk of severe disease. In the CLEVER study, infants were randomised to receive a single intramuscular dose of Enflonsia or a placebo. Findings showed a safety profile comparable to placebo. Interim results from the SMART trial, which compared Enflonsia with the generic palivizumab in higher-risk infants, indicated a similar safety profile between the two treatments. The most commonly reported adverse reactions included injection-site pain, redness and swelling, as well as rash, with the majority described as mild to moderate.

Enflonsia is already approved in the US, Canada and Switzerland, with further regulatory submissions ongoing in other markets.

In parallel research, scientists in China established a cohort of 10 pediatric health care workers who have worked at a children's hospital for more than 10 years and isolated immune cells from them. In comparison with 14 healthy adults, the team found that RSV-specific neutralizing antibody titers in the pediatricians were more than threefold higher than those in individuals without occupational exposure to RSV/hMPV. The team then selected three pediatricians with high neutralizing titers for their study.

Upon further analysis, the team identified three monoclonal antibodies, referred to as CNR2056, CNR2053 and CNR2047. CNR2056 and CNR2053 were found to neutralize RSV A and B strains, while CNR2047 neutralized both RSV and hMPV. All exhibited potent neutralizing activity when characterized for binding and neutralization.

Animal studies on cotton rats and mice showed that CNR2056 and CNR2053 provided prophylactic protection against RSV in cotton rats. While a benchmark achieved reduced viral titers or complete viral clearance at a maximum dose of 2 mg/kg, CNR2053 and CNR2056 enabled viral clearance at lower doses of 1 and 0.5 mg/kg, respectively. When the team tested the efficacy of CNR2047 in cotton rats, they found a more than 100-fold reduced viral replication in two RSV strains. hMPV studies with CNR2047 resulted in complete protection from hMPV infection in the lungs of mice and a dose-dependent reduction in pulmonary inflammation.

Combining the mAbs into cocktails expanded coverage and reduced risk of escape variants. The researchers hope to expand on their work, and human trials will need to occur before these preventive therapies become available.

While RSV vaccines exist, they are currently only approved for older adults, as pediatric vaccines have faced safety challenges associated with enhanced respiratory disease risks. There are currently no approved therapies or prophylactics for hMPV.