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

Business Wire

09-06-2025

BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has approved ENFLONSIA™ (clesrovimab-cfor) for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates (newborns) and infants who are born during or entering their first RSV season. ENFLONSIA is a preventive, long-acting monoclonal antibody (mAb) designed to provide direct, rapid and durable protection through 5 months, a typical RSV season, with the same 105 mg dose regardless of weight. A typical RSV season usually spans autumn to spring of the next year.
'RSV disease is the leading cause of infant hospitalization in the U.S. and can lead to serious respiratory conditions like bronchiolitis and pneumonia,' said Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude Children's Research Hospital and investigator for the CLEVER (MK-1654-004) and SMART (MK-1654-007) trials. 'ENFLONSIA combines dosing convenience with strong clinical data showing significant reductions in RSV disease incidence and hospitalizations, making it a promising new intervention to help protect infants from RSV.'
ENFLONSIA should not be administered to infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA. See additional Selected Safety Information below.
The approval is based on results from the pivotal Phase 2b/3 CLEVER trial (MK-1654-004) evaluating a single dose of ENFLONSIA administered to 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.
The approval is also supported by results from the Phase 3 SMART trial (MK-1654-007) evaluating the safety and efficacy of ENFLONSIA versus palivizumab in infants at increased risk for severe RSV disease.
'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.'
The U.S. Centers for Disease Control and Prevention's (CDC's) Advisory Committee on Immunization Practices is expected to meet later this month to discuss and make recommendations for the use of ENFLONSIA in infants. Ordering is anticipated to begin in July, with shipments delivered before the start of the 2025-2026 RSV season.
About ENFLONSIA™ (clesrovimab-cfor)
ENFLONSIA (clesrovimab-cfor) is Merck's extended half-life monoclonal antibody (mAb) indicated for passive immunization for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in newborns and infants who are born during or entering their first RSV season. ENFLONSIA is administered using non-weight-based dosing and is designed to provide direct, rapid and durable protection through 5 months, a typical RSV season. For infants born during the RSV season, ENFLONSIA is to be administered starting from birth. For infants born outside of the RSV season, ENFLONSIA should be administered prior to the start of their first RSV season. For infants undergoing cardiac surgery with cardiopulmonary bypass during or entering their first RSV season, an additional 105 mg dose is recommended as soon as the infant is stable after surgery.
Selected Safety Information for ENFLONSIA (clesrovimab-cfor)
Do not administer ENFLONSIA to infants with a history of serious hypersensitivity reactions, including anaphylaxis, to any component of ENFLONSIA.
Serious hypersensitivity reactions, including anaphylaxis, have been observed with other human immunoglobulin G1 (IgG1) monoclonal antibodies. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, initiate appropriate medications and/or supportive therapy.
The most common adverse reactions were injection-site erythema (3.8%), injection-site swelling (2.7%) and rash (2.3%).
About Clinical Trials and Data Supporting U.S. FDA Approval
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 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 health care provider visits in settings such as outpatient clinic, clinical study site, emergency department, urgent care center and/or hospital. 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 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 ENFLONSIA (N=446) or palivizumab (N=450) by IM 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 palivizumab and consistent with the safety profile of ENFLONSIA in infants in the CLEVER trial. The efficacy of ENFLONSIA in infants at increased risk for severe RSV disease was established by extrapolation of efficacy of ENFLONSIA from the CLEVER trial to the SMART trial based on similar pharmacokinetic exposure. The incidence rates of RSV-associated MALRI requiring ≥1 indicator of LRI or severity and RSV-associated hospitalization were generally comparable between ENFLONSIA (3.6%, 95% CI: 2.0, 6.0 and 1.3%, 95% CI: 0.4, 2.9, respectively) and palivizumab (2.9%, 95% CI: 1.5, 5.2 and 1.5%, 95% CI: 0.5, 3.2, respectively) through Day 150 (5 months).
In clinical trials, when ENFLONSIA was given concomitantly with routine childhood vaccines, the safety profile of the co-administered regimen was generally comparable to the safety profile when ENFLONSIA and childhood vaccines were administered alone.
About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.
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Please see Prescribing Information for ENFLONSIA (clesrovimab-cfor) at https://www.merck.com/product/usa/pi_circulars/e/enflonsia / enflonsia_pi.pdf and Patient Information/Medication Guide for ENFLONSIA at https://www.merck.com/product/usa/pi_circulars/e/enflonsia / enflonsia_ppi.pdf.