ENFLONSIA (Clesrovimab) RSV Monoclonal Antibody Clinical Trials, Dosage, Indication, Side Effects
Merck's ENFLONSIA (Clesrovimab, MK-1654) is an approved, extended half-life monoclonal antibody (mAb) developed as a passive immunization to prevent Respiratory syncytial virus (RSV). Clesrovimab is designed to be administered as a single dose, regardless of birth weight. It is being studied in healthy preterm, full-term, and at-risk infants to provide direct, rapid, and durable protection through their first RSV season against mild, moderate, and severe RSV.
On June 9, 2025, Merck announced that the U.S. Food and Drug Administration (FDA) had approved ENFLONSIA™, designed to provide direct, rapid, and durable protection for up to 5 months, a typical RSV season, at a single 105 mg dose, regardless of weight. The FDA's approval is based on results from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004), which evaluated a single dose of ENFLONSIA in preterm and full-term infants (birth to 1 year of age). The trial met its primary and key secondary endpoints, as outlined below. ENFLONSIA demonstrated a reduction in incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥1 indicator of lower respiratory infection (LRI) or severity compared to placebo through 5 months (primary endpoint) by 60.5% (95% CI: 44.2, 72.0, p<0.001) (incidence rates: ENFLONSIA, 0.026; placebo, 0.065). ENFLONSIA demonstrated a reduction in RSV-associated hospitalizations through 5 months (key secondary endpoint) by 84.3% (95% CI: 66.7-92.6, p < 0.001) (incidence rates: ENFLONSIA, 0.004; placebo, 0.024), showing increasing efficacy with increasing disease severity.
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U.S. CDC ACIP ENFLONSIA (Clesrovimab) Presentation
Anushua Sinha, MD, MPH, Clinical Director of Vaccines Clinical Research at Merck & Co., Inc., presented "Clesrovimab (MK-1654): Pediatric Clinical Program" on October 23, 2024, to the U.S. CDC's Advisory Committee on Immunization Practices (ACIP). On February 26-28, 2025, Dr. Helen Chu (ACIP, WG Chair) is scheduled to lead discussions on Introduction, Evidence to Recommendations, and Clinical Considerations.
U.S. FDA ENFLONSIA (Clesrovimab)
The U.S. Food and Drug Administration (FDA) accepted the Biologics License Application for clesrovimab (MK-1654) on December 17, 2024.
ENFLONSIA Indication
Patient Information/Medication Guide for ENFLONSIA. RSV is the leading cause of hospitalization for healthy infants under a year old and a significant cause of death in low- and middle-income countries. RSV can lead to serious respiratory conditions like bronchiolitis and pneumonia. The U.S. CDC says it is not possible to know the exact number of people who have experienced illness from RSV in the U.S. because not everyone who contracts RSV will seek medical care or get tested for RSV. Before your child receives ENFLONSIA, tell their healthcare provider about all of your child’s medical conditions. Do not administer ENFLONSIA to infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA.
ENFLONSIA Dosage
In a clinical study, clesrovimab was given as a single injection in four different dose groups (preterm: 20, 50, 75, or 100 mg, full-term: 100 mg) and compared to a placebo. In clinical trials, when ENFLONSIA was administered concomitantly with routine childhood vaccines, the safety profile of the co-administered regimen was generally comparable to that when ENFLONSIA and childhood vaccines were administered alone.
Long-acting Monoclonal Antibody Effectiveness
The administration of a long-acting monoclonal antibody reduced the risk of hospitalization for an RSV infection by approximately 80% in children under 6 months of age. Effectiveness was similar for intensive care admission and the need for mechanical ventilation, as well as for different RSV subgroups. In contrast, effectiveness was slightly lower for children born preterm, with low birth weight, or from multiple pregnancies.
ENFLONSIA News
June 9, 2025 - “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 U.S. 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.”
December 17, 2024 - "Despite recent advances in RSV prevention, unmet needs remain for additional effective interventions to help protect infants and continue to help address the burden RSV places on families and the healthcare system. This regulatory milestone, along with promising results from our pivotal studies demonstrating efficacy in the prevention of RSV disease, marks important progress toward our goal of having clesrovimab available in time for the 2025-26 RSV season," said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories.
November 27, 2024 - A study reported that Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies, supporting its ongoing development in late-stage trials.
October 17, 2024 - Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude's Children's Research Hospital and investigator for the MK-1654-004 and MK-1654-007 trials, commented: "The MK-1654-004 study evaluated a broad spectrum of RSV disease ranging from mild outpatient illness to severe disease requiring hospitalization. These promising results demonstrating decreased incidence of RSV disease, including hospitalizations, highlight the potential for clesrovimab to play an important role in helping to alleviate the continued burden of RSV on infants and their families."
July 23, 2024 - Topline Results from the Phase 2b/3 Trial of Clesrovimab announced.
Clesrovimab Clinical Trials
The CLEVER trial (MK-1654-004) (NCT04767373) was a Phase 2b/3, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of ENFLONSIA in early and moderate preterm infants (≥29 to <35 weeks gestational age [GA]) and late preterm and full-term infants (≥35 weeks GA) entering their first RSV season. Participants were randomized 2:1 to receive a single 105 mg dose of ENFLONSIA (N = 2,411) or a saline placebo (N = 1,203) by intramuscular (IM) injection.
The primary endpoint was the incidence of participants with RSV-associated medically attended lower respiratory infection (MALRI) characterized as cough or difficulty breathing and requiring ≥1 indicator of LRI (wheezing, rales/crackles) or severity (chest wall in-drawing/retractions, hypoxemia, tachypnea, dehydration due to respiratory symptoms) from Day 1 through Day 150 (5 months) after dosing. Medically attended includes all healthcare provider visits in settings such as outpatient clinics, clinical study sites, emergency departments, urgent care centers, and/or hospitals. The key secondary endpoint was RSV-associated hospitalization through Day 150 (5 months).
The trial demonstrated that the safety profile of ENFLONSIA in infants entering their first RSV season was generally comparable to that of the placebo. The most common adverse reactions were injection-site erythema occurring within 5 days post-dose (ENFLONSIA: 3.8%; placebo: 3.3%), injection-site swelling occurring within 5 days post-dose (ENFLONSIA: 2.7%; placebo: 2.6%), and rash occurring within 14 days post-dose (ENFLONSIA: 2.3%; placebo: 1.9%). Participants were monitored for serious adverse events (SAEs) through the duration of their participation for up to 365 days post-dose. Most (≥97%) of the adverse reactions were toxicity grade 1 (mild) or grade 2 (moderate).
The SMART trial (MK-1654-007) (NCT04938830) was a Phase 3, randomized, partially-blind, palivizumab-controlled, multi-site trial to evaluate the safety and efficacy of ENFLONSIA in infants at increased risk of severe RSV disease, including early (<29 weeks GA) or moderate preterm infants (≥29 to ≤35 weeks GA) and infants with chronic lung disease of prematurity or congenital heart disease of any GA. Participants were randomized 1:1 to receive either ENFLONSIA (N = 446) or palivizumab (N = 450) by intramuscular injection.
Among infants at increased risk of severe RSV disease and entering their first RSV season, the trial demonstrated that the safety profile of ENFLONSIA was generally comparable to that of palivizumab and consistent with the safety profile observed in infants in the CLEVER trial. The efficacy of ENFLONSIA in infants at increased risk for severe RSV disease was established by extrapolating the efficacy of ENFLONSIA from the CLEVER trial to the SMART trial, based on similar pharmacokinetic exposure.