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The investigational monoclonal antibody clesrovimab protected against respiratory syncytial virus (RSV) disease and prevented RSV hospitalizations among healthy preterm- and term infants, according to results of a phase IIb/III study.

A single dose of clesrovimab reduced the incidence of RSV-associated medically attended lower respiratory infections (MALRI) that had at least one indicator of LRI or severity by 60.4% when compared with placebo through 5 months after treatment (95% CI 44.1-71.9, P<0.001), reported Anushua Sinha, MD, MPH, of Merck, at the annual IDWeek meeting in Los Angeles.

Clesrovimab also reduced RSV-associated hospitalizations by 84.2% (95% CI 66.6-92.6, P<0.001).

In addition, at 5 months post-dose, the monoclonal antibody also reduced RSV-associated:

• Acute respiratory infections by 52% (95% CI 39.5-61.9)
• Hospitalization associated with lower respiratory infection by 90.9% (95% CI 76.2-96.5)
• Severe MALRI by 91.7% (95% CI 62.9-98.1)

"RSV requires no introduction. It's the most common cause of hospitalization in infants in their first year of life," Sinha told attendees.

"Clesrovimab administered as a single dose for infants of all weights provided protection against mild, moderate, and severe RSV disease in healthy infants, and that included both preterm and term gestational ages," Sinha said.

MALRI requiring at least one indicator of LRI or severe disease was defined as an RSV-positive real-time PCR nasopharyngeal sample, plus cough and/or difficulty breathing, and at least one of the following: wheezing, chest wall in-drawing/retractions, hypoxemia, tachypnea, or dehydration due to respiratory symptoms.

Results were similar and consistent through 6 months after dosing. Also, efficacy against RSV subtypes A and B were generally consistent with the overall efficacy estimates, although confidence intervals were somewhat wider, Sinha said.

Clesrovimab is an extended half-life RSV neutralizing antibody in development for all infants in their first RSV season and for infants and children under the age of 2 years at increased risk for severe disease and entering their second RSV season. It is administered as a single, 105-mg intramuscular dose.

Clesrovimab "achieves high nasal tissue distribution with high proportion of serum to nasal tissue partitioning," Sinha explained.

"Did you see any difference in the estimated efficacies if you looked at those babies 29 to 35 weeks of gestational age compared to 35 weeks or older?" asked session moderator Judith Guzman-Cottrill, DO, of Oregon Health & Science University in Portland.

"That's an important question and we're in the process of conducting subanalyses that look at those groups of gestational age as well as chronological age, weight, and a number of other factors," that will be presented in the near future, Sinha said.

Currently, (Beyfortus) is recommended as an option to protect against RSV in infants up to age 19 months to prevent RSV. Clesrovimab differs from nirsevimab in that it binds to the RSV fusion protein site IV, whereas nirsevimab targets site Ø.

Another monoclonal antibody, palivizumab (Synagis), is approved for the prevention of RSV, but only in infants ages ≤6 months born prematurely or older infants diagnosed with certain types of lung or heart conditions.

Safety was also a primary endpoint of the study. Overall, any adverse events (AEs), drug-related AEs, serious drug-related AEs, and deaths were similar between the clesrovimab and placebo groups. The majority of AEs were mild or moderate. There was one grade 3 AE of urticaria in the clesrovimab group but was not considered related to the study. There were seven deaths in the clesrovimab group (0.3%) and three in the placebo group (0.2%), but no deaths were considered related to the study intervention or to RSV.

In the phase IIb portion of the study, 300 healthy preterm and full-term infants 29 weeks of gestational age or older and entering their first RSV season were randomized 2:1 to either clesrovimab 105 mg IM or placebo (0.9% NaCl). This group was followed through 515 days. The phase III portion of the study enrolled an additional 3,334 infants who were randomized 2:1 to either the treatment or placebo group. The first 1,350 participants were followed through day 515 and the remaining were followed through day 365.

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