Clesrovimab-cfor, a fully human recombinant monoclonal antibody directed against the fusion (F) surface glycoprotein of respiratory syncytial virus (RSV), is an antiviral agent.1
Clesrovimab-cfor is used 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.1
There are no data regarding co-administration of clesrovimab-cfor with other immunoglobulin products.1 There are no data regarding the substitution of clesrovimab-cfor for palivizumab once prophylaxis is initiated with palivizumab for the RSV season.1
Prevention of Lower Respiratory Tract Disease Caused by RSV
The efficacy and safety of clesrovimab-cfor for the prevention of RSV lower respiratory tract disease in neonates and infants born during or entering their first RSV season were evaluated in 2 pivotal clinical trials; one study was conducted with healthy infants and the second with infants at high risk for development of severe RSV disease.1, 2
The first trial was a Phase 2b/3, randomized, double-blind, placebo-controlled trial conducted across 22 countries, which included healthy infants born at ≥29 weeks' gestational age stratified by region (Northern or Southern Hemisphere), chronological age, and gestational age: moderate preterm infants (≥29 to <35 weeks gestational age) and late preterm and full-term infants (≥35 weeks gestational age).1, 2 The primary efficacy endpoint was the incidence of RSV-associated medically attended lower respiratory infection within 150 days post-dose, defined as respiratory symptoms (cough or difficulty breathing) with additional clinical findings (e.g., wheezing, retractions, hypoxemia, tachypnea) and a laboratory confirmation by RSV reverse transcription-polymerase chain reaction (RT-PCR) nasopharyngeal sample.1, 2 Infants received a single 105 mg IM dose of clesrovimab-cfor or placebo.1, 2 The median age of the 3,614 enrolled infants was 3.1 months (range, 0-12 months of age), with 80% of infants <6 months of age and 16% of infants ≥6 to <9 months of a 51% were male, 18% were born at 29 to <35 weeks gestational age, 45% were White, 27% were Asian, 14% were Black, 12% were multi-racial, and 28% were Hispanic.1, 2 Medically attended lower respiratory infection occurred in 2.6% (60/2,411) of infants receiving clesrovimab-cfor versus 6.5% (74/1,203) receiving placebo, corresponding to a 60.5% relative risk reduction.1, 2 RSV-associated hospitalization occurred in 0.4% of infants receiving clesrovimab-cfor versus 2.4% receiving placebo, an 84.3% relative risk reduction.1, 2
A second randomized, partially blinded, palivizumab-controlled, Phase 3 trial was conducted in 27 countries to evaluate the safety, and efficacy of clesrovimab-cfor in infants at increased risk for severe RSV disease who were born during or entering their first RSV season.1, 2 Eligible participants included infants ≤35 weeks gestational age and infants with chronic lung disease of prematurity or congenital heart disease of any gestational a all infants had a chronological age of birth to one year.1, 2 A secondary objective was to evaluate the safety and efficacy of administering an additional dose of clesrovimab-cfor at the start of the second RSV season in high-risk infants who remained at increased risk for severe RSV disease.1, 2 The trial was not powered to detect a difference between treatment groups, and efficacy in high-risk infants was extrapolated from healthy preterm and term infants based on comparable pharmacokinetics.1, 2 Infants were randomized to receive either a single 105 mg IM dose of clesrovimab-cfor on day 1, followed by a dose of placebo one month later, or palivizumab 15 mg/kg monthly for 3-5 doses.1, 2 Infants who underwent extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass received a second dose of clesrovimab-cfor.1, 2 In the second RSV season, approximately 300 high-risk infants were re-dosed with clesrovimab-cfor.1, 2 The median age of the 896 infants enrolled was 2.5 months (range, 0-12 months of age), with 89% <6 months of a 50% were male, 28% had chronic lung disease, 11% had chronic heart disease, 55% were ≥29 weeks gestational age without chronic lung or heart disease, and 6% were <29 weeks gestational age without chronic lung or heart disease, 52% were White, 18% were Asian, 15% were Black, 12% were multi-racial, and 32% were Hispanic.1, 2 Through 150 days after dosing, the incidence of RSV-associated medically attended lower respiratory infection was 3.6% with clesrovimab-cfor and 2.9% with palivizumab, while RSV-associated hospitalization occurred in 1.3% and 1.5% of infants, respectively.1, 2 Data regarding the efficacy of a second dose of clesrovimab-cfor during a second season of RSV are unavailable.2
The American Academy of Pediatrics (AAP) and the Centers for Disease Control and Prevention (CDC) recommend RSV immunization with a long-acting monoclonal antibody (nirsevimab or clesrovimab) for infants <8 months of age who are born during or entering their first RSV season if not adequately protected by maternal vaccination (unvaccinated, unknown status, or <14 days since vaccination).6, 7 Administration of infant RSV antibody is recommended during October through March in most of the US.6, 7 The dose should be administered ideally during the birth hospitalization if born from October through March or before RSV season onset if born outside this period.6, 7 Both the AAP and CDC note that nirsevimab and clesrovimab may also be considered in special circumstances, such as inadequate maternal antibody transfer or in infants who undergo cardiopulmonary bypass or ECMO, which can lower circulating antibody levels.6, 7 Only children 8-19 months of age who are at high risk for severe disease should receive RSV immunization in their second RSV season; nirsevimab is FDA-labeled for this indication, and clesrovimab is not.6, 7 High-risk conditions include chronic lung disease of prematurity, significant immunocompromise, severe cystic fibrosis, and American Indian/Alaska Native children.6, 7 Palivizumab is no longer routinely recommended and will be discontinued by December 31, 2025.6, 7
Dispensing and Administration Precautions
Administer clesrovimab-cfor as a single IM injection in the anterolateral aspect of the thigh; avoid gluteal region and areas near major nerve trunks/blood vessels.1
Clesrovimab-cfor is available as 105 mg/0.7 mL in a single-dose prefilled syringe for IM injection; the solution is clear to slightly opalescent and colorless to slightly yellow.1
Do not use the prefilled syringe if there is particulate matter, discoloration, damage, a broken security seal, or if expired or dropped.1
Remove clesrovimab-cfor from the refrigerator and let the prefilled syringe sit at room temperature for about 15 minutes before injection.1
To administer clesrovimab-cfor, hold the syringe barrel and twist the tip cap counterclockwise detaching the Luer Lock adaptor or finger flange extender.1 Attach a sterile Luer Lock needle by twisting clockwise until secure.1 Use a 22-25 gauge needle due to product viscosity.1
If co-administered with vaccines, inject at a separate site with a separate syrin do not mix with vaccines or medications in the same syringe/vial.1
Keep refrigerated (2-8°C); protect from light in original carton.1 Can be stored at room temperature (20-25°C) for up to 48 hours and then used or discarded; do not freeze or shake.1
For neonates and infants born during the respiratory syncytial virus (RSV) season, administer 105 mg of clesrovimab-cfor as a single IM injection once starting from birth.1
For infants born outside the RSV season, administer 105 mg of clesrovimab-cfor as a single IM injection once prior to the start of their first RSV season considering the duration of protection provided by the drug.1
For infants undergoing cardiac surgery with cardiopulmonary bypass during or entering their first RSV season, administer an additional 105 mg IM dose postoperatively as soon as the infant is stable.1
Hypersensitivity Including Anaphylaxis
Serious hypersensitivity reactions, including anaphylaxis, have occurred with other human immunoglobulin G1 (IgG1) monoclonal antibodies; if such reactions occur with clesrovimab-cfor, provide appropriate medications and supportive care.1
RSV Diagnostic Test Interference
Clesrovimab-cfor may interfere with immunologically-based respiratory syncytial virus (RSV) rapid antigen tests; if results are negative but clinical signs suggest RSV, confirm with a reverse transcriptase polymerase chain reaction (RT-PCR) assay.1
The incidence of anti-drug antibodies (ADA) with clesrovimab-cfor varied by assay method, limiting cross-study comparisons.1 Following the approved dosage in RSV season 1, ADA developed in ≤6% of infants by day 150 and in ≤13% by day 240.1 ADA occurrence did not appear to affect pharmacokinetics, RSV neutralizing activity, or safety.1 The impact of ADA occurrence on efficacy is unknown because of the low incidence of ADA development and medically attended disease in clinical trials.1
Clesrovimab-cfor is not indicated for use in females of childbearing potential.1
Clesrovimab-cfor should not be used in females of childbearing potential.1
Safety and effectiveness of clesrovimab-cfor in preventing RSV lower respiratory tract disease have been demonstrated in neonates and infants during their first RSV season; safety and efficacy have not been established in children >12 months of age.1
The most frequently reported adverse reactions were injection-site erythema (3.8%), injection-site swelling (2.7%), and rash (2.3%).1
Since clesrovimab-cfor is eliminated through catabolism, metabolic drug-drug interactions are not expected, although no formal interaction studies have been conducted.1
In clinical trials, concomitant administration of clesrovimab-cfor and routine childhood vaccines showed a safety profile comparable to that observed when clesrovimab-cfor and the vaccines were given separately.1
Clesrovimab-cfor is a recombinant human immune globulin G1 (IgG1) kappa neutralizing monoclonal antibody that provides passive immunity by targeting the extracellular domain of the respiratory syncytial virus (RSV) fusion protein; the antibody contains a YTE triple amino acid substitution (M252Y, S254T, T256E) in the Fc region, which increases binding to the neonatal Fc receptor resulting in an extended serum half-life.1 Clesrovimab-cfor binds to a conserved epitope on antigenic site IV of the RSV fusion protein, blocking viral-cell membrane fusion and entry.1
Clesrovimab-cfor demonstrated potent in vitro neutralizing activity against both RSV A and B.1 Historical isolates (1987-2016) had median EC50 values of 25 picomolar (pM) for RSV A and 30 pM for RSV B, while contemporary isolates (2016-2021) showed higher median EC50 values of 121 pM for RSV A and 130 pM for RSV B, likely due to assay differences rather than reduced susceptibility.1 The RSV site targeted by clesrovimab-cfor is highly conserved (i.e., almost identical in over 99% of RSV samples tested worldwide). 1
In RSV infections, amino acid changes in the clesrovimab-cfor binding site occurred more often in treated infants than in placebo recipients.1 Most involved the G446 residue, which can cause marked (>1,000-fold) loss of drug activity in lab testing.1 While these resistance-associated substitutions were occasionally linked to hospitalization in isolated cases, no consistent association was found between their presence and RSV-related medically attended lower respiratory infection or hospitalization overall.1
Clesrovimab-cfor retained activity in vitro against RSV A and B variants with resistance-associated substitutions to palivizumab or nirsevimab, including N262Y (palivizumab) and several nirsevimab-associated substitutions.1 Conversely, nirsevimab and palivizumab remained active against RSV variants with clesrovimab-cfor resistance-associated substitutions G446E and G446W.1 Not all nirsevimab resistance-associated substitutions have been tested for cross-resistance.1
In infants receiving a single 105 mg IM dose of clesrovimab-cfor, serum RSV neutralizing antibody titers increased to about 7 times baseline within 4 hours and peaked by day 7, with levels correlating to serum drug concentration.1 No significant relationship was observed between drug exposure and RSV-associated medically attended lower respiratory infection outcomes.1 Clinical trial data indicate that a single dose of clesrovimab-cfor provides protection for up to 5 months.1
In infants, the pharmacokinetics of clesrovimab-cfor are approximately dose-proportional after a single IM dose of 20-210 mg.1 Serum exposures were similar across neonates and infants, preterm infants ≤35 weeks gestational age and those <29 weeks gestational age, and infants with chronic lung disease or congenital heart disease.1 The median time to maximum concentration is 6.5 days with a terminal half-life of about 44 days.1 The drug is degraded into small peptides via catabolic pathways, and pharmacokinetics are not significantly affected by race or risk for severe RSV disease, or expected to be altered by renal or hepatic impairment.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IM use | 105 mg/0.7 mL | Enflonsia® | Merck Sharp & Dohme |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Merck Sharp & Dohme LLC. ENFLONSIA® (CLESROVIMAB) INTRAMUSCULAR prescribing information. 2025 Jun. [Web]
2. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 761432Orig1s000: Integrated review. [Web]
6. Committee on Infectious Diseases; Recommendations for the Prevention of RSV Disease in Infants and Children: Policy Statement. Pediatrics 2025; 10.1542/peds.2025-073923. [Web]
7. Centers for Disease Control and Prevention (CDC). RSV Immunization Guidance for Infants and Young Children. 2025 Aug 18. [Web]