Written and Reviewed By: Pharmacally Medical News Desk
Respiratory Syncytial Virus (RSV) is one of the most significant threats to infant health worldwide. Every year, RSV is responsible for an estimated 12.9 million lower respiratory tract infections and 2.2 million hospitalizations in children under one year of age. Preterm babies and those with chronic illnesses are at higher risk. Most RSV-related hospitalizations actually occur in healthy full-term infants. The first six months of life are particularly vulnerable and preventive options are limited till today.
Understanding RSV in Infants
Respiratory syncytial virus (RSV) is a highly contagious RNA virus that spreads through droplets and contaminated surfaces, commonly infecting infants through close contacts. After initial infection of the nose and throat, it can progress to the lower airways, causing inflammation, mucus plugging, and airway narrowing that may lead to bronchiolitis or pneumonia. Most infants develop only cold-like symptoms, but in those under six months, preterm babies, or those with underlying conditions, RSV can cause severe disease, hypoxemia, and hospitalization. Globally, RSV is the leading cause of infant hospitalization and is linked to later wheezing and asthma, with the highest mortality seen in low- and middle-income countries. For decades, management was limited to supportive care, as ribavirin proved ineffective and unsafe. Palivizumab offered protection only to high-risk infants through costly monthly injections. It was seen that vaccine was ineffective; however recent advances shows nirsevimab effective in seasonal protection and maternal vaccination for passive immunity. RSV posed serious illness threat to healthy infants, showing the need for a single-dose, broadly effective preventive option like clesrovimab.
About Clesrovimab
Clesrovimab is a long-acting recombinant human monoclonal antibody developed by Merck Sharp & Dohme (MSD); it provides season-long protection against respiratory syncytial virus (RSV) infection in infants with a single intramuscular injection. It is engineered with YTE substitutions (M252Y, S254T, T256E) in the Fc region, which prolong its half-life by enhancing binding to the neonatal Fc receptor, allowing the drug to remain in circulation at protective levels for several months. Clesrovimab binds to site IV on the RSV fusion (F) glycoprotein enabling it to block viral entry at multiple stages and lowering the risk of resistance. Surveillance studies show that this target is conserved in over 99.8% of RSV A and B strains. The major advantage of clesrovimab compared with earlier preventive options is that it provides durable, broad protection across all RSV subtypes with its single, fixed, non–weight-based dosing which simplifies administration for doctors and offering effective protection for both preterm and full-term healthy infants throughout an entire RSV season.
Clinical Evidence – CLEVER Trial
The CLEVER trial (MK-1654-004, ClinicalTrials.gov ID: NCT04767373) was a phase 2b–3, randomized, double-blind, placebo-controlled international study designed to evaluate the efficacy and safety of clesrovimab in preventing RSV lower respiratory tract disease in infants. The trial was conducted across 22 countries; enrolled 3,632 healthy preterm and full-term infants younger than one year who were entering their first RSV season. Infants eligible for palivizumab prophylaxis, those with a recent febrile illness, or prior RSV preventive treatment were excluded. Participants were randomly assigned in a 2:1 ratio to receive a single intramuscular dose of clesrovimab (105 mg) or placebo, with stratification based on gestational age, chronological age and geographic hemisphere. The primary endpoint was RSV-associated medically attended lower respiratory tract infection (LRTI) within 150 days of dosing, confirmed by RT-PCR and clinical signs of infection. The key secondary endpoint was RSV-associated hospitalization during the same period, while additional endpoints included severe LRTI, all-cause LRTI, and pharmacokinetic and immunogenicity assessments. Out of 3,614 infants who received injections, 2,398 received clesrovimab and 1,201 received placebo. Results showed RSV-associated medically attended LRTI in 2.6% of clesrovimab recipients versus 6.5% with placebo, corresponding to a 60.4% efficacy. RSV-related hospitalization occurred in 0.4% versus 2.3%, yielding an 84.2% efficacy. In post hoc analyses, efficacy reached up to 88–92% against severe RSV infections. The protective effect was consistent across RSV A and B subtypes, age, weight, and regions. Overall, the CLEVER trial demonstrated that a single fixed dose of clesrovimab provides strong, durable protection against RSV disease and hospitalization in both preterm and full-term infants.
Safety profile
Clesrovimab safety in the CLEVER trial was similar to placebo; most adverse events were mild in nature like injection-site reactions such as pain or erythema, irritability, somnolence, decreased appetite and low-grade fever. The majority of reactions were grade 1–2. Serious adverse events occurred at similar rates in both groups (11.5% with clesrovimab and 12.4% with placebo). Deaths were rare and not attributed to the drug or RSV. There was one investigator-reported grade-2 bronchospasm early after dosing and one grade-3 urticaria in the clesrovimab arm, both nonfatal and not judged related to drug exposure.
Regulatory status-mid-September 2025
The U.S. Food and Drug Administration granted approval for clesrovimab under the brand name Enflonsia (clesrovimab-cfor) in June 2025 for prevention of RSV lower respiratory tract disease in neonates and infants entering their first RSV season. Shortly thereafter the European Medicines Agency’s CHMP adopted a positive opinion recommending marketing authorization for Enflonsia on 18 September 2025, and that positive opinion is now with the European Commission for the formal EU decision.
Conclusion
The CLEVER trial evidence shows that a single 105 mg intramuscular dose of clesrovimab provides durable, clinically meaningful protection against RSV lower respiratory disease and critically reduces RSV-related hospitalizations in healthy preterm and full-term infants. With U.S. approval already granted and a positive CHMP opinion in mid-September 2025, clesrovimab (Enflonsia) becomes an important addition to the preventive treatment for RSV. It simplifies seasonal protection by using a fixed, non-weight-based dose, targets a highly conserved site on the F protein and can significantly reduce infant morbidity and health-system strain during peak RSV season.
Reference
Heather J. Zar, Eric A.F. Simões, Shabir A. Madhi et al, Clesrovimab for Prevention of RSV Disease in Healthy Infants, The New England Journal of Medicine, September 17, 2025 DOI: 10.1056/NEJMoa2502984
Merck Receives Positive EU CHMP Opinion for ENFLONSIA™ (clesrovimab) for the Prevention of Respiratory Syncytial Virus (RSV) in Infants During Their First RSV Season, 19 Sept 2025, Merk, https://www.merck.com/news/merck-receives-positive-eu-chmp-opinion-for-enflonsia-clesrovimab-for-the-prevention-of-respiratory-syncytial-virus-rsv-in-infants-during-their-first-rsv-season/
U.S. FDA Approves Merck’s ENFLONSIA™ (clesrovimab-cfor) for Prevention of Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Disease in Infants Born During or Entering Their First RSV Season, 09 June 2025, https://www.merck.com/news/u-s-fda-approves-mercks-enflonsia-clesrovimab-cfor-for-prevention-of-respiratory-syncytial-virus-rsv-lower-respiratory-tract-disease-in-infants-born-during-or-entering-their-fir/
Highlight of Prescribing Information, ENFLONSIA™ (clesrovimab-cfor) injection, for intramuscular use https://www.merck.com/product/usa/pi_circulars/e/enflonsia/enflonsia_pi.pdf