The Food and Drug Administration (FDA) has approved Enflonsia™ (clesrovimab-cfor) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants who are born during or entering their first RSV season.
Enflonsia is an extended half-life RSV fusion glycoprotein neutralizing monoclonal antibody.
The product is administered as a single intramuscular (IM) injection using the same dose regardless of weight.
The approval was supported by data from 2 clinical trials: the phase 2b/3 CLEVER trial (ClinicalTrials.gov Identifier: NCT04767373), which included healthy preterm and full-term infants, and the phase 3 SMART trial (ClinicalTrials.gov Identifier: NCT04938830), which compared the safety and tolerability of clesrovimab with palivizumab in infants and children at high risk for severe RSV disease due to prematurity, chronic lung disease of prematurity, or hemodynamically significant congenital heart disease.
In the CLEVER trial, study participants (infants born at ≥29 weeks gestational age from birth up to 1 year entering their first RSV season) were randomly assigned 2:1 to receive a single 105mg dose of clesrovimab (n=2411) or saline placebo (n=1203). The primary endpoint was the incidence of RSV-associated medically attended lower respiratory infection (MALRI), defined as at least 1 indicator of lower respiratory infection (LRI) or severity through 150 days after dosing.
Findings showed clesrovimab significantly reduced the incidence of RSV-associated MALRI requiring at least 1 indicator of LRI or severity by 60.5% (95% CI, 44.2-72.0; P <.001). The incidence rates for MALRI (requiring ≥1 indicator of LRI or severity) over 5 months were 0.026 and 0.065 in the clesrovimab and placebo arms, respectively.
Clesrovimab also significantly reduced RSV-associated hospitalizations vs placebo through 5 months (key secondary endpoint) by 84.3% (95% CI, 66.7-92.6; P <.001). The incidence rates for hospitalization over 5 months were 0.004 and 0.024 in the clesrovimab and placebo arms, respectively.
In the SMART study, infants and children at high risk for severe RSV disease were randomly assigned 1:1 to receive clesrovimab 105mg IM on day 1 and placebo on day 28 (n=446) or monthly palivizumab (n=450).
Results showed the incidence rate of RSV-associated MALRI requiring at least 1 indicator of LRI or severity through 150 days was 3.6% (95% CI, 2.0-6.0) in clesrovimab-treated patients compared with 2.9% (95% CI, 1.5-5.2) in palivizumab-treated patients. Additionally, the incidence rates of RSV-associated hospitalization through day 150 were found to be comparable between clesrovimab and palivizumab (1.3% [95% CI, 0.4-2.9] and 1.5% [95% CI, 0.5-3.2], respectively).
The most common adverse reactions reported with clesrovimab were injection site erythema, injection site swelling, and rash.
“Enflonsia provides an important new preventive option to help protect healthy and at-risk infants born during or entering their first RSV season with the same dose regardless of weight,” said Dr Dean Y. Li, president, Merck Research Laboratories. “We are committed to ensuring availability of Enflonsia in the US before the start of the upcoming RSV season to help reduce the significant burden of this widespread seasonal infection on families and health care systems.”
Enflonsia is supplied in a single-dose prefilled syringe containing 105mg/0.7mL of solution.
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