At a Glance
- Merck announced SMART trial results showing ENFLONSIA’s safety across two RSV seasons in high-risk children under 2 years (mostly CLD/CHD).
- AEs consistent (irritability 13%); serum levels match CLEVER trial, supporting efficacy extrapolation.
- Interim data comparable to palivizumab drove FDA approval (June 2025) for first-season prevention.
- Merck seeks expanded label for high-risk second-season use via regulators
Written By: Pharmacally Medical News Desk
Merck announced positive Phase 3 SMART trial data for ENFLONSIA (clesrovimab) at RSVVW’26, demonstrating consistent safety across two RSV seasons in infants and children under 2 years at high risk for severe RSV disease.
The findings support efficacy extrapolation for a second-season dose in vulnerable groups like those with chronic lung disease or congenital heart disease.
Dr. Macaya Douoguih, vice president and Therapeutic Area Head of Global Clinical Development at Merck Research Laboratories, noted RSV as a leading global cause of infant hospitalization, especially severe in high-risk children under 2 years, positioning ENFLONSIA as a vital option while Merck pursues worldwide access for eligible infants and children through regulatory submissions.
Trial Overview
The SMART trial (NCT04938830) is a randomized, palivizumab-controlled study evaluating ENFLONSIA’s safety, efficacy, and pharmacokinetics in preterm infants or those with chronic lung disease (CLD) or congenital heart disease (CHD). In season 1, infants received 105 mg ENFLONSIA or monthly palivizumab; season 2 involved an open-label 210 mg ENFLONSIA dose in 276 high-risk children under 2 years. Nearly all season 2 participants (99%) had CLD or CHD, reflecting their elevated risk.
Season 1 Key Results
Safety profiles were comparable between ENFLONSIA and palivizumab, with solicited adverse events (AEs) like irritability (28.8% vs. 33.7%) and injection-site reactions similar across arms. No drug-related serious AEs occurred with ENFLONSIA; RSV-associated medically attended lower respiratory infection (MALRI) rates were 3.2% (ENFLONSIA) vs. 3.4% (palivizumab) through day 150. These interim data, alongside CLEVER trial (NCT04767373) results, supported FDA approval in June 2025 for first season use in neonates and infants.
Season 2 Findings
In season 2, safety remained consistent with season 1, with solicited AEs including irritability (13.0%) and somnolence (8.7%); no drug-related serious AEs reported. Serum concentrations matched those in healthy CLEVER trial infants, enabling efficacy extrapolation for high-risk children. MALRI incidence was 7.3% and hospitalization 3.0% through day 180, aligning with higher baseline risks post-COVID.
Safety Profile and Administration
ENFLONSIA, a long-acting monoclonal antibody, uses a fixed 105 mg dose (or 210 mg for season 2 as two injections) for 5-month protection, regardless of weight. Common AEs include injection-site erythema (3.8%) and rash (2.3%); contraindications cover hypersensitivity history. It may interfere with RSV antigen tests, warranting RT-PCR confirmation.
Regulatory and Clinical Implications
Dr. Paolo Manzoni, Head of Maternal–Infant Medicine at University of Torino Hospital Degli Infermi, Ponderano, Italy, and SMART trial investigator, stated that all second-season ENFLONSIA recipients were high-risk children nearly all with chronic lung disease or congenital heart disease and the findings demonstrate ENFLONSIA’s potential to protect these vulnerable patients who may need a second dose.
Merck plans to submit season 2 data to FDA and global authorities for expanded labeling in high-risk children under 2 years. Currently approved in the US, Canada, and others for first season use, ENFLONSIA addresses RSV’s role as a top infant hospitalization cause.
Reference
Merck Announces Positive New Data for ENFLONSIA™ (clesrovimab) for Infants and Children Under 2 Years of Age at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease Over Two RSV Seasons, 19 February 2026, Merck Announces Positive New Data for ENFLONSIA™ (clesrovimab) for Infants and Children Under 2 Years of Age at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease Over Two RSV Seasons – Merck.com
Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007) (SMART), ClinicalTrials.gov ID NCT04938830, https://clinicaltrials.gov/study/NCT04938830
Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) (CLEVER), ClinicalTrials.gov ID NCT04767373, https://clinicaltrials.gov/study/NCT04767373