What evidence and recommendations support the use of clesrovimab for prevention of RSV?
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Background
Respiratory syncytial virus (RSV) is a common respiratory illness that usually causes mild symptoms.1 However, severe illness may occur and is most common in infants, older adults, people with conditions that cause immunocompromise, and young children and adults with certain risk factors. As such, it is the leading cause of hospitalization in infants. In the United States, RSV season begins in the fall and peaks in winter. Several RSV immunization options are available for RSV prevention, including vaccines and monoclonal antibodies.
Three vaccines are available for adults to prevent infection: RSV vaccine, adjuvanted (Arexvy), mRNA RSV vaccine (MResvia®), and RSV vaccine (Abrysvo®).2 Abrysvo is also FDA-approved for immunization of pregnant individuals at 32 to 36 weeks gestation to prevent severe lower respiratory tract disease in infants from birth through 6 months of age.3 In infants, several monoclonal antibodies are available for immunization. 4,5 Nirsevimab (Beyfortus®) was FDA- approved in 2023, and more recently clesrovimab (EnflonsiaTM) was FDA-approved in 2025, providing another option for patients. 6,7 Palivizumab, a short-acting monoclonal antibody requiring multiple doses, is no longer recommended for routine use, and the manufacturer plans to discontinue production by December 2025.4 This article will review the available information for the use of clesrovimab, including evidence and guideline recommendations.
RSV monoclonal antibody characteristics
Clesrovimab and nirsevimab are long-acting monoclonal antibodies administered as a single-dose.4 Unlike vaccines that mount an immune response, monoclonal antibodies provide passive immunity by targeting the prefusion confirmation of the RSV F protein.5-7 Table 1 outlines the drug characteristics of recommended monoclonal antibodies, including indication, dosing, and notable safety information.
table 1
| Table 1. Drug characteristics of recommended monoclonal antibodies for RSV6,7 | ||
|---|---|---|
| Clesrovimab | Nirsevimab | |
| FDA-approved indication | Prevention of RSV lower respiratory tract disease in infants born during or entering their first RSV season | Prevention of RSV lower respiratory tract disease in infants born during or entering their first RSV season Prevention of RSV lower respiratory tract disease in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season |
| Dosage | 105 mg IM as a single dose | Infants in their first RSV season: 50 mg IM if < 5 kg; 100 mg IM if ≥ 5 kg Children entering their second RSV season: 200 mg IM |
| Warnings and precautions | Potential for interference with immunologically based RSV diagnostic assays (such as rapid antigen tests) Hypersensitivity reactions have been reported | Use with caution in patients with bleeding disorders due to risk of bleeding with IM injection Hypersensitivity reactions have been reported |
| Abbreviations: FDA=Food and Drug Administration; IM=intramuscularly; RSV=respiratory syncytial virus. | ||
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Clinical data for clesrovimab
Clesrovimab was evaluated in 2 clinical trials in infants (Table 2). 6,8,9 As of August 2025, both clinical trials are unpublished, and details are available from the product information and conference abstracts. Compared to placebo, clesrovimab was 60.5% effective in preventing RSV-associated medically attended lower respiratory tract infection (MALRI) (95% confidence interval [CI], 44.2 to 72). In trials, MALRI was defined as having a cough or difficulty breathing with ≥ 1 indicator of lower respiratory infection (such as wheezing, rales, or crackles) or severity (such as chest wall in-drawing/retractions, hypoxemia, tachypnea, or dehydration due to respiratory symptoms). Cases were considered to be medically attended if it was attended to in any healthcare setting, such as an outpatient clinic, clinical study site, emergency department, urgent care, or hospital. The effectiveness was considered successful per investigators, since the lower bound of the 95% CI was > 25%.
Clesrovimab was compared to palivizumab in 1 clinical trial. 6,9 Patients were included if they were either preterm (≤35 weeks gestational age) or had chronic lung disease of prematurity or congenital heart disease. Of the included patients, 28% had chronic lung disease and 11% had congenital heart disease. The incidence of RSV-associated MALRI was 3.6% (95% CI, 2 to 6) with clesrovimab and 2.9% (95% CI, 1.5 to 5.2) with palivizumab, though direct comparison was not performed.
table 2
| Table 2. Clinical trials for clesrovimab for the prevention of RSV. 6,8,9 | |||
|---|---|---|---|
| Study design and Duration | Subjects | Interventions | Results |
| CLEVER (NCT04767373) 6,8 Phase 2b/3, DB, PC, RCT 150 days (5 months) | N=3,614 infants aged 0 to 12 months (median 3.1 months) in first RSV season, born at ≥ 29 weeks GA | Single dose of Clesrovimab 105 mg IM (n=2,411) Placebo (n=1,203) | Primary: RSV-associated MALRI during first RSV season: 60 cases vs. 74 cases; efficacy, 60.5% (95% CI, 44.2 to 72; p<0.001) Secondary: RSV-associated hospitalization during first RSV season: 9 cases vs. 28 cases; efficacy, 84.3% (95% CI, 66.7 to 92.6; p<0.001) Safety: Adverse effects that occurred more commonly than placebo included injection-site erythema (3.8% vs. 3.3%), injection site swelling (2.7% vs. 2.6%), and rash (2.3% vs. 1.9%) |
| SMART (NCT04938830) 6,9 Phase 3, AC, partially-blind, RCT 150 days | N=896 infants aged 0 to 12 months (median 2.5 months) in first RSV season, either born at ≤ 35 weeks GA or with CLD of prematurity or hemodynamically significant CHD | Single dose of Clesrovimab 105 mg IM on day 1, then placebo 1 month later (n=446) Palivizumab 15 mg/kg IM on day 1, then monthly for 3 to 5 doses total (n=450) | Primary: RSV-associated MALRI: 3.6% with clesrovimab vs. 2.9% with palivizumab (p-value not reported) Secondary: RSV-associated hospitalization: 1.3% with clesrovimab vs. 1.5% with palivizumab (p-value not reported) Safety: Adverse effects were similar between clesrovimab and palivizumab |
| Abbreviations: AC=active-controlled; CI=confidence interval; CLD=chronic lung disease; CHD=congenital heart disease; DB=double-blind; GA=gestational age; IM=intramuscular; MALRI=medically attended lower respiratory infection; PC=placebo-controlled; RCT=randomized controlled trial; RSV=respiratory syncytial virus. | |||
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Recommendations for RSV prophylaxis in Infants
The Centers for Disease Control and Prevention (CDC) and AAP provide recommendations for RSV prophylaxis in infants. 4,5 Both guidelines recommend either RSV vaccination of the birthing parent during pregnancy with Abrysvo or infant immunization with a monoclonal antibody. For immunization with monoclonal antibodies, recommendations state to give 1 dose of clesrovimab or nirsevimab for infants < 8 months old going into their first RSV season meeting one of the following criteria:
- birthing parent did not receive vaccination during pregnancy
- birthing parent vaccine status is unknown
- infant was born < 14 days following RSV vaccination of the parent.
A dose of clesrovimab or nirsevimab can also be considered in infants who were born ≥ 14 days after the birthing parent received an RSV vaccination when there may be benefit. This includes infants born to a birthing parent who may not mount an adequate response; infants born to a birthing parent with a medical condition associated with reduced placental antibody transfer (such as HIV); and infants with a history of cardiopulmonary bypass or extracorporeal membrane oxygenation, causing loss of maternal antibodies. A monoclonal antibody dose may also be considered following maternal vaccination if there is an increased risk for severe RSV infection in the infant, such as in the setting of hemodynamically significant congenital heart disease or an intensive care admission with oxygen at discharge.
For infants born during RSV season who are indicated for a monoclonal antibody, AAP recommends giving RSV immunization within 1 week of birth. 4 For infants with prolonged hospitalizations at birth, RSV immunization may be timed to occur shortly before or after discharge. For those born outside of RSV season, immunization may occur at any regular, well-child visit.
In young children aged 8 to 19 months who are at increased risk for severe RSV infection, nirsevimab is recommended before or early in the second RSV season.4,5 Populations at increased risk include American Indian or Alaska Native children; children with chronic lung disease of prematurity requiring medical support in the 6 months prior to the second RSV season; children with severe immunocompromise; or children with cystic fibrosis with either (1) severe lung disease or (2) weight-for-length < 10th percentile. Clesrovimab is not indicated for patients > 8 months old.
Conclusion
Clesrovimab is a monoclonal antibody option for the prevention of RSV in infants born during or entering their first RSV season. 6 Guidelines recommend that all infants receive immunization for their first RSV season either through vaccination of the birthing parent with Abrysvo or administration of a monoclonal antibody. 4,5 There is no preference between nirsevimab and clesrovimab. Notably, guidelines recommend nirsevimab for infants 8 to 19 months old who remain at risk for severe RSV disease entering their second RSV season, while clesrovimab is not indicated for this use. The approval of clesrovimab serves as an additional option to improve drug access, mitigate potential drug shortages, and address health disparities in the prevention of RSV in infants.
References
- Centers for Disease Control and Prevention (CDC). Clinical Overview of RSV. CDC Website. Updated July 8, 2025. Accessed August 19, 2025.
- Centers for Disease Control and Prevention (CDC). RSV vaccine guidance for adults. CDC Website. Updated July 8, 2025. Accessed August 19, 2025.
- Abrysvo. Package Insert. Pfizer, Inc.; 2025.
- Recommendations for the Prevention of RSV Disease in Infants and Children: Policy Statement. Pediatrics. 2025. doi:10.1542/peds.2025-073923
- Centers for Disease Control and Prevention (CDC). RSV immunization guidance for infants and young children. CDC Website. Updated August 30, 2024. Accessed August 19, 2025. https://www.cdc.gov/rsv/hcp/vaccine-clinical-guidance/infants-young-children.html.
- Enflonsia. Package insert. Merck Sharp & Dohme LLC; 2025.
- Beyfortus. Package Insert. Sanofi Pasteur Inc.; 2024.
- A Phase 2b/3 Study to Evaluate the Efficacy and Safety of an Investigational Respiratory Syncytial Virus (RSV) Antibody, Clesrovimab, in Healthy Preterm and Full-Term Infants. Presentation #166 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.
- Phase 3, Randomized, Controlled Trial Evaluating Safety, Efficacy, and Pharmacokinetics (PK) of Clesrovimab in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease. Presentation #167 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.
Prepared by:
Amanda Gerberich, PharmD, BCPS
Clinical Assistant Professor, Drug Information Specialist
University of Illinois at Chicago College of Pharmacy
September 2025
The information presented is current as August 19, 2025. This information is intended as an educational piece and should not be used as the sole source for clinical decision-making.