Merck’s ENFLONSIA Receives Positive CHMP Opinion in Europe for Expanded RSV Prevention in High-Risk Children Up to 24 Months
Merck & Co, known as MSD outside the United States and Canada, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending an expanded indication for ENFLONSIA® (clesrovimab). The recommendation covers the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in children up to 24 months of age who remain at increased risk of developing severe RSV disease through their second RSV season.
The positive CHMP opinion represents an important regulatory milestone for Merck as it seeks to expand access to ENFLONSIA among vulnerable infants and young children who continue to face an elevated risk of serious RSV-related complications beyond their first year of life.
Following the CHMP recommendation, the application will be reviewed by the European Commission (EC), which is responsible for granting marketing authorization across the European Union (EU), as well as Iceland, Liechtenstein, and Norway. A final regulatory decision is expected within the next two months.
If approved, the expanded indication would provide an additional preventive option for eligible children who remain vulnerable to severe RSV infection during their second RSV season. This is particularly important for children with certain underlying medical conditions, including chronic lung disease and congenital heart disease, as well as some children born prematurely who have additional risk factors.
ENFLONSIA was initially approved by the U.S. Food and Drug Administration (FDA) in June 2025 for the prevention of RSV-related lower respiratory tract disease in infants born during or entering their first RSV season. The European Commission subsequently approved the medicine in April 2026 for the same first-season preventive indication.
The proposed expansion builds on the medicine’s existing regulatory approvals and Merck’s broader efforts to improve protection against RSV among infants and children at increased risk of severe disease.
Positive CHMP Opinion Supports Expanded Protection During the Second RSV Season
The latest recommendation from the CHMP addresses an important gap in RSV prevention for children whose vulnerability to severe disease continues beyond their first RSV season.
Although many children experience RSV infections during early childhood, certain populations face a greater likelihood of developing serious complications. Children with underlying respiratory or cardiovascular conditions and those with specific complications associated with premature birth may remain at increased risk of severe RSV disease during their second RSV season.
RSV can cause significant respiratory illness, particularly in infants and young children. In more serious cases, the infection can lead to bronchiolitis or pneumonia, potentially requiring hospitalization and additional medical intervention.
For children with pre-existing health conditions, an RSV infection can place additional strain on the respiratory and cardiovascular systems, increasing the likelihood of severe outcomes.
The proposed expanded indication for ENFLONSIA is intended to address these ongoing risks by extending preventive protection to eligible children up to 24 months of age.
Dr. Macaya Douoguih, Vice President, Therapeutic Area Head, Global Clinical Development at Merck Research Laboratories, emphasized the importance of extending RSV prevention to children who remain vulnerable after their first RSV season.
Douoguih explained that the risk of severe RSV disease does not necessarily end after a child’s first season of exposure. Some children continue to face an increased risk of serious RSV-related bronchiolitis and pneumonia, conditions that can result in hospitalization.
She described the positive CHMP opinion as an important step toward making ENFLONSIA available to eligible children in the European Union during their second RSV season.
The recommendation reflects Merck’s continued focus on developing preventive approaches for vulnerable pediatric populations and expanding access to medicines that address serious infectious diseases.
ENFLONSIA: A Preventive Antibody Against RSV Lower Respiratory Tract Disease
ENFLONSIA, also known as clesrovimab, is a preventive medicine developed by Merck to reduce the risk of RSV lower respiratory tract disease in infants and eligible young children.
The medicine is designed to provide passive immunity against RSV through an antibody-based approach. Unlike vaccines that stimulate the body’s immune system to generate its own immune response, preventive monoclonal antibodies provide targeted antibodies that can help protect against infection-related complications.
One distinguishing feature of ENFLONSIA is its administration without the need for weight-based dosing in infants.
According to Merck, ENFLONSIA is the first and only preventive option against RSV lower respiratory tract disease administered to infants without requiring weight-based dosing.
This characteristic may simplify dosing considerations for healthcare professionals and caregivers, particularly when administering preventive treatment to infants with different body weights.
The medicine was initially developed to provide protection during an infant’s first RSV season, when exposure to the virus can result in significant respiratory illness.
With the proposed expanded indication, Merck aims to extend its potential use to children under two years of age who remain at increased risk of severe RSV disease during their second season.
The expanded indication would therefore address a broader pediatric population with specific medical vulnerabilities.
Phase 3 SMART Trial Supports Expanded Indication
The positive CHMP opinion is supported by clinical evidence from Merck’s Phase 3 SMART clinical trial, also known as study MK-1654-007 (NCT04938830).
The SMART study evaluated the safety and efficacy of ENFLONSIA in infants and children under two years of age who were considered at increased risk of developing severe RSV disease across two RSV seasons.
The trial was designed to investigate the potential benefits of preventive treatment in children who may require additional protection because of underlying medical conditions or other risk factors.
The clinical evidence generated through the programme has supported Merck’s efforts to expand the medicine’s indication beyond its original first-season use.
Results from the SMART trial were presented in February 2026 at RSVVW’26, the ninth conference of the Respiratory Syncytial Virus Foundation (ReSViNET).
The clinical findings were subsequently published in two scientific journals, providing additional information about the medicine’s performance and safety.
Interim results covering the first RSV season were published in September 2025 in the New England Journal of Medicine. The full results from the study were later published in JAMA Pediatrics in July 2026.
Publication in peer-reviewed journals provides healthcare professionals and researchers with access to detailed clinical evidence and supports further scientific evaluation of ENFLONSIA’s potential role in RSV prevention.
The SMART trial findings form the clinical foundation for the expanded indication now recommended by the CHMP.
Understanding Respiratory Syncytial Virus and Its Impact on Children
Respiratory syncytial virus is a common respiratory virus that can cause infections affecting the lungs and respiratory tract. Although many infections result in mild, cold-like symptoms, RSV can lead to serious illness in infants and young children.
The virus is a major cause of lower respiratory tract infections during early childhood and can contribute to significant healthcare utilization, particularly among infants and children with underlying medical conditions.
Common RSV symptoms include:
- Coughing and sneezing.
- Runny nose and nasal congestion.
- Fever.
- Reduced appetite.
- Wheezing and breathing difficulties.
In more severe cases, RSV can cause bronchiolitis, an inflammation of the small airways in the lungs, or pneumonia, an infection that affects the lung tissue.
These complications may interfere with normal breathing and oxygen delivery, sometimes requiring hospitalization and supportive medical care.
Young infants are particularly vulnerable because their respiratory systems are still developing. Children with chronic lung disease or congenital heart disease may face additional challenges when infected with RSV.
Premature birth can also increase the likelihood of severe respiratory complications, especially when accompanied by other medical risk factors.
While many children recover from RSV without significant complications, those at elevated risk may require more intensive monitoring and preventive interventions.
Importantly, RSV infection does not necessarily provide lasting protection against future infections. Children may become infected more than once, and some remain vulnerable to severe disease during subsequent RSV seasons.
This makes preventive strategies particularly relevant for high-risk children who continue to face an increased risk of serious respiratory complications after their first year of life.
Specific High-Risk Pediatric Groups May Benefit From Expanded Prevention
The proposed expanded indication for ENFLONSIA focuses on children under two years of age who have an increased risk of severe RSV disease through their second RSV season.
The targeted population includes certain children born with chronic lung disease, congenital heart disease, and those born early or moderately preterm who have additional qualifying risk conditions.
Chronic lung disease can affect respiratory function and reduce a child’s ability to manage additional respiratory infections. An RSV infection may further aggravate existing pulmonary complications.
Similarly, congenital heart disease can place additional demands on the cardiovascular system. When a child with an underlying heart condition develops a respiratory infection, the resulting illness may create additional physiological stress.
Children born prematurely may also have underdeveloped respiratory systems and other medical vulnerabilities that increase their susceptibility to severe RSV-related complications.
For these populations, extending preventive protection into the second RSV season could represent an important development in pediatric respiratory disease management.
Merck’s regulatory application seeks to address this need by expanding the population eligible to receive ENFLONSIA, subject to the final approval of the European Commission.
ENFLONSIA Expands Its Global Regulatory Presence
ENFLONSIA has established a growing international regulatory presence since its initial approvals.
The medicine is currently approved in more than 55 countries worldwide, including the United States, Canada, China, Japan, and the European Union.
Its initial regulatory approvals have focused on preventing RSV lower respiratory tract disease in infants born during or entering their first RSV season.
The U.S. FDA approved ENFLONSIA in June 2025, followed by European Commission approval in April 2026.
These approvals represented important milestones in Merck’s efforts to introduce an additional preventive option for infants at risk of RSV-related respiratory illness.
The company is also pursuing regulatory submissions in additional countries to expand the medicine’s availability across international markets.
In parallel, Merck is seeking to extend the approved indication to include eligible children under two years of age who remain at increased risk of severe RSV disease during their second RSV season.
The latest positive CHMP opinion represents progress toward this objective in Europe.
U.S. FDA Review Underway for Expanded Pediatric Indication
In addition to the European regulatory process, Merck is pursuing an expanded indication for ENFLONSIA in the United States.
The FDA has accepted a supplemental Biologics License Application (sBLA) seeking to update the medicine’s indication to include the prevention of RSV lower respiratory tract disease in children under two years of age who remain at increased risk of severe RSV disease through their second RSV season.
The agency has assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 22, 2027.
The acceptance of the sBLA represents another important regulatory development for Merck’s expansion strategy.
If approved, the expanded U.S. indication would allow eligible high-risk children to receive ENFLONSIA for RSV prevention beyond their first season, according to the proposed labeling.
The parallel regulatory activities in the United States and Europe demonstrate Merck’s efforts to pursue broader access to its preventive antibody across major healthcare markets.
The company is also continuing regulatory work in countries where ENFLONSIA has already been approved, while pursuing additional applications in new markets.
Merck Strengthens Its Commitment to Pediatric RSV Prevention
The positive CHMP opinion represents a significant step in Merck’s broader strategy to strengthen pediatric RSV prevention and address the needs of children who remain vulnerable to severe respiratory infections.
By seeking to expand ENFLONSIA’s indication to include eligible children up to 24 months of age, the company aims to address an important gap in preventive care for high-risk pediatric populations.
The clinical evidence from the Phase 3 SMART trial, together with the medicine’s existing approvals in more than 55 countries, provides the foundation for its continued regulatory development.
The European Commission will now review the CHMP recommendation before making a final decision on marketing authorization across the EU, Iceland, Liechtenstein, and Norway. A decision is expected within the next two months.
Meanwhile, the U.S. FDA is reviewing Merck’s supplemental application, with a target action date of March 22, 2027.
If the expanded indications receive approval, ENFLONSIA could provide an additional preventive option for children whose risk of serious RSV-related complications extends beyond their first RSV season.
For Merck, these regulatory developments reinforce its commitment to advancing preventive medicines and improving protection for vulnerable children worldwide. The company’s ongoing global regulatory efforts are intended to broaden access to RSV prevention while addressing the medical needs of pediatric populations who face an increased risk of severe disease.
About the Phase 3 SMART trial
The SMART trial (MK-1654-007) (NCT04938830) was a Phase 3, randomized, partially-blind, palivizumab-controlled, multicenter study to evaluate the safety, efficacy and pharmacokinetics of ENFLONSIA in infants and children at increased risk for severe RSV disease over two RSV seasons. The trial enrolled early (<29 weeks gestational age [GA]) or moderate preterm infants (≥29 to ≤35 weeks GA) and infants with chronic lung disease (CLD) of prematurity or congenital heart disease (CHD) of any GA.
In RSV season 1, participants were randomized 1:1 to receive either a 105 mg dose of ENFLONSIA (n=502) or monthly palivizumab (n=501) by intramuscular (IM) injection. In RSV season 2, eligible participants (children under 2 years of age with CLD, CHD or early or moderate preterm birth with certain risk conditions) received an additional open-label 210 mg dose of ENFLONSIA by IM injection (n=276). Nearly all participants (99%) who received ENFLONSIA in RSV season 2 had CLD (n=229) or CHD (n=43).
About RSV globally
Respiratory syncytial virus (RSV) is a contagious virus that causes widespread seasonal infections and can lead to serious respiratory conditions such as bronchiolitis and pneumonia. As a leading cause of hospitalization among infants globally, there is persisting unmet need for RSV preventive options for both healthy and high-risk infants during their first RSV season as well as for children at increased risk for severe RSV disease through their second RSV season. RSV season is the time of year when RSV infections are most common, usually occurring autumn through spring of the next year in temperate climates. Timing and severity in a given community or region can vary year to year.
About ENFLONSIA® (clesrovimab-cfor) in the U.S.
ENFLONSIA is Merck’s FDA-approved extended half-life monoclonal antibody (mAb) indicated for passive immunization for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in newborns and infants who are born during or entering their first RSV season. ENFLONSIA is administered using the same dose regardless of weight (105 mg/0.7 mL in a prefilled syringe) 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 within the first week of life. For infants born outside of the RSV season, ENFLONSIA should be administered shortly before the RSV season begins. 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. ENFLONSIA has a 30-month shelf life.