Enflonsia (clesrovimab-cfor) / Merck (MSD) - LARVOL DELTA

Respiratory syncytial virus immunization in children: The old, the new and what's just around the corner. (PubMed, Hum Vaccin Immunother) - "Until recently, immunization was limited to high-risk infants and children, including those born prematurely or with significant co-morbidities, via monthly dosing with the monoclonal antibody (mAb) palivizumab. Recent approvals of long-acting mAb nirsevimab and the maternal RSV pre-fusion F vaccine combined with other anticipated options such as long-acting mAb clesrovimab, and future pediatric vaccines, signal a shift in RSV immunization...We report findings from a survey assessing the level of immunization acceptance among Canadian parents. Provision of education through healthcare professionals, printed materials, parent groups, social media, and the internet were recommended."

Journal • Review • Infectious Disease • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

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 (Merck (MSD) Press Release) - "Merck...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....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 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."

FDA approval • Infectious Disease • Respiratory Syncytial Virus Infections

IMPACT OF THE EXTRACORPOREAL MEMBRANE OXYGENATION AND CARDIOPULMONARY BYPASS ON THE PHARMACOKINETICS OF CLESROVIMAB (ESPID 2025) - "A phase 3 palivizumab-controlled study (SMART) evaluated the safety, efficacy, and pharmacokinetics (PK) of clesrovimab in infants and children at increased risk for severe RSV disease, including infants with hemodynamically significant congenital heart disease (HS-CHD). However, serum concentrations post ECMO or CPB were consistently below the predicted median concentration (Figure 1; GMR, 0.49 [95% CI 0.30-0.80]). Conclusions/Learning Points Clesrovimab concentrations decreased after ECMO or CPB, suggesting a need for post-procedure dose of clesrovimab for infants who continue to require protection against RSV disease."

PK/PD data • Infectious Disease • Respiratory Syncytial Virus Infections

COST-EFFECTIVENESS OF NIRSEVIMAB AND CLESROVIMAB TO PREVENT RESPIRATORY SYNCYTIAL VIRUS LOWER RESPIRATORY TRACT DISEASE (RSV-LRTD) IN INFANTS IN THE UNITED STATES (US) (ESPID 2025) - "Conclusions/Learning Points Nirsevimab is cost-effective in preventing RSV-LRTD in all infants compared to palivizumab with a lower ICER than clesrovimab. When compared directly, nirsevimab was cost-saving and a dominant strategy against clesrovimab."

Cost effectiveness • HEOR • Infectious Disease • Respiratory Syncytial Virus Infections

SAFETY OF CLESROVIMAB IN INFANTS AT INCREASED RISK FOR SEVERE RSV DISEASE IN RSV SEASON 1: SUBGROUP ANALYSIS OF A PHASE 3 TRIAL (MK-1654-007, SMART) (ESPID 2025) - P3 | "Safety summary of clesrovimab vs. palivizumab in high-risk infants for RSV disease: Interim results from phase 3 trial (MK-1654-007, SMART) in RSV season 1 Conclusions/Learning Points Safety results were generally comparable between the clesrovimab and the palivizumab groups across predefined subgroup categories in RSV season 1, consistent with the overall population. Limitations include small numbers of participants in certain subgroups."

Clinical • P3 data • Infectious Disease • Respiratory Syncytial Virus Infections

DEVELOPMENT OF HIGH ANTIDRUG ANTIBODY TITERS IN CLESROVIMAB CLINICAL TRIALS IS ASSOCIATED WITH RSV EXPOSURE BEYOND DAY 150 (ESPID 2025) - "Conclusions/Learning Points In clesrovimab-treated infants, exposure to RSV beyond day 150 and into the second RSV season is associated with high-titer ADA. Infants who developed ADA had higher RSV SNA titers compared to those who did not develop ADA."

Clinical • Infectious Disease • Respiratory Syncytial Virus Infections

POPULATION PHARMACOKINETICS OF CLESROVIMAB FOR THE PREVENTION OF RSV DISEASE IN INFANTS – EXTRAPOLATION OF EFFICACY TO INFANTS AT INCREASED RISK (ESPID 2025) - P2/3, P3 | "The Phase 3 study (SMART, NCT04938830) evaluated safety, efficacy, and pharmacokinetics (PK) of clesrovimab in infants and children at increased risk for severe RSV disease (i.e. chronic lung disease, congenital heart disease, and prematurity) and eligible to receive palivizumab. Overall, PK exposures in SMART can be considered generally comparable to the PK exposures in CLEVER. Conclusions/Learning Points The PK of clesrovimab for infants in CLEVER and SMART receiving 105-mg IM dose during RSV Season 1 was generally comparable, supporting extrapolation of efficacy to infants at increased risk."

Clinical • PK/PD data • Infectious Disease • Respiratory Syncytial Virus Infections

EVALUATING THE PUBLIC HEALTH IMPACT OF CLESROVIMAB IN THE UNITED STATES: MEDICALLY ATTENDED RSV CASES AVERTED AND NUMBER NEEDED TO IMMUNIZE (ESPID 2025) - P2/3 | "The estimated cases averted and NNI for all-cause LRI hospitalization were 90,272 (95% CI, 41,481-146,184) and 41 (95% CI, 26-89), respectively. Conclusions/Learning Points These findings highlight the potential public health impact of clesrovimab, and its potential role as an effective strategy to reduce the burden of RSV disease and associated health care resource utilization."

Clinical • Infectious Disease • Respiratory Syncytial Virus Infections

COMPREHENSIVE ANALYSIS OF CLESROVIMAB EPITOPE SUBSTITUTIONS AT SITE IV OF THE RSV F PROTEIN FROM THE LITERATURE, SURVEILLANCE, AND A CLINICAL TRIAL (ESPID 2025) - P2/3 | "Conclusions/Learning Points The high conservation of the clesrovimab epitope in circulating RSV strains suggests that viral escape due to natural mutations at the clesrovimab binding site is infrequent. These findings support the continued development of clesrovimab for the prevention of RSV disease in infants."

Clinical • Infectious Disease • Respiratory Syncytial Virus Infections

EFFICACY AND SAFETY OF CLESROVIMAB, AN RSV-NEUTRALIZING MONOCLONAL ANTIBODY, IN HEALTHY INFANTS: SUBGROUP ANALYSES OF THE CHINA COHORT IN THE PHASE 2B/3 TRIAL (CLEVER) (ESPID 2025) - P2/3 | "The incidences of AEs and serious AEs (SAEs) were comparable between intervention groups, with no reported anaphylaxis/hypersensitivity AE of special interest, treatment-related SAEs, or deaths. Conclusions/Learning Points A single dose of clesrovimab reduced RSV-associated MALRI and hospitalization and was well-tolerated in healthy preterm and full-term infants in China, consistent with the overall study population."

Clinical • P2/3 data • P2b data • Infectious Disease • Respiratory Syncytial Virus Infections

EFFICACY AND SAFETY OF CLESROVIMAB, AN INVESTIGATIONAL RSV ANTIBODY, IN HEALTHY PRETERM AND FULL-TERM INFANTS: SUBGROUP ANALYSES OF A PHASE 2B/3 TRIAL (CLEVER) (ESPID 2025) - P2/3 | "Within each subgroup analyzed, safety results (including injection site reactions, systemic, intervention-related, and serious adverse events) were generally comparable between intervention groups. Conclusions/Learning Points The results of this analysis support the efficacy of clesrovimab in healthy infants, independent of weight or gestational or chronological age."

Clinical • P2/3 data • P2b data • Prematurity • Infectious Disease • Respiratory Syncytial Virus Infections

Supporting Pediatric RSV Clinical Trials Through Close Epidemiological Surveillance During the SARS-CoV-2 Pandemic. (PubMed, Pharmacol Res Perspect) - "Clesrovimab, an extended half-life monoclonal antibody, aims to protect infants for an entire RSV season...Near real-time monitoring of data showed minimal RSV activity in 2020. In 2021, RSV resurged early in some countries and was delayed in others, resulting in a change in trial enrollment strategy."

Journal • Infectious Disease • Novel Coronavirus Disease • Pediatrics • Respiratory Diseases

Human iPS cell-derived respiratory organoids as a model for respiratory syncytial virus infection. (PubMed, Life Sci Alliance) - "Furthermore, RSV infection was significantly inhibited by monoclonal antibodies (nirsevimab, palivizumab, suptavumab, or clesrovimab), although ribavirin showed limited efficacy. These findings highlight the utility of respiratory organoids for RSV research."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Efficacy of monoclonal antibodies and maternal vaccination for prophylaxis of respiratory syncytial virus disease. (PubMed, Commun Med (Lond)) - "Modeling can be used to reliably predict the efficacy of maternal vaccination for preventing RSV in infants. Passive immunization (e.g., with clesrovimab) is likely to provide more protection for preterm infants and for infants born outside the RSV season than that provided by current maternal vaccines. Maternal vaccination may provide partial protection from RSV disease to full-term infants born just prior to or during the RSV season."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

IS01 - Advancements in paediatric RSV prevention: navigating the evolving clinical landscape and public health strategies (ESCMID Global 2025) - "MSD will present a symposium highlighting current and rapidly evolving clinical landscape and public health strategies in the prevention of pediatric RSV. The symposium will include major themes: - RSV Burden of Disease - Paediatric acute infection; hospitalisation, severe disease - Associated long-term morbidity (asthma, recurrent wheezing, acute otitis media, etc.) - Public health implementation experience with monoclonal antibodies (mAbs) - best practices, successes, clinical learnings - Clesrovimab unique characteristics and mechanism of action - high nasal concentration at the site of infection, binding affinity, duration of protection - Clinical trial data of clesrovimab - efficacy and safety, protocols 004/007"

Clinical • Asthma • Immunology • Infectious Disease • Otorhinolaryngology • Pediatrics • Respiratory Diseases • Respiratory Syncytial Virus Infections

Anti-Idiotypic Antibody as a Booster Vaccine Against Respiratory Syncytial Virus. (PubMed, Vaccines (Basel)) - "It is the precursor for MK1654 (clesrovimab), which successfully completed a Phase III clinical trial...In an immunogenicity study, mice primed with RSV F and boosted with 1A6 Fab showed a site IV-specific antibody response with a concurrent increase in RSV virus neutralization. These results suggest that anti-IDs could be potentially used as booster vaccines for specific epitopes."

Journal • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • RB1

The recent landscape of RSV vaccine research. (PubMed, Ther Adv Vaccines Immunother) - "Historically, prevention in infants was limited to the mAb palivizumab, which, despite its efficacy, was costly and inaccessible in many regions. Recent advancements include nirsevimab, a long-acting mAb that has shown substantial efficacy in reducing medically attended RSV-related disease in infants, in phase III clinical trials, early regional and national real-world data...Promising candidates in development include the mAb clesrovimab, which has an extended half-life and high levels in the nasal epithelial lining and high safety and efficacy profiles in late-stage trials...With the ongoing rollout of the recently licenced vaccines and mAbs internationally, the landscape of RSV care is rapidly changing. We also must ensure these advances reach those in LMICs who need these therapies most."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Development of high titer anti-drug antibodies in a Phase 1b/2a infant clesrovimab trial are associated with RSV exposure beyond day 150. (PubMed, J Infect Dis) - "RSV exposure in infants beyond day 150 after dosing is associated with ADA development and high RSV-SNA titers with no impact on pharmacokinetics."

Journal • P1/2 data • Respiratory Syncytial Virus Infections

A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants. (PubMed, J Infect Dis) - P1/2 | "Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies supporting its ongoing development in late-stage trials."

Journal • P1/2 data • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Clesrovimab Long-Acting Antibody for the Prevention of RSV Disease in Infants: Results from the Pivotal Phase 2b/3 Studies (WVCE 2024) - No abstract available

P2/3 data • P2b data • Respiratory Syncytial Virus Infections

Clesrovimab Binding Site Conservation on the RSV F Protein: An Evaluation of RSV Molecular Sequencing Data from 2019-2023 and GenBank Sequence Analysis (IDWeek 2024) - No abstract available

Infectious Disease

Clesrovimab Binding Site Conservation on the RSV F Protein: An Evaluation of RSV Molecular Sequencing Data from 2019-2023 and GenBank Sequence Analysis (IDWeek 2024) - No abstract available

Infectious Disease

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development. (PubMed, Rev Med Virol) - "Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633."

Journal • Review • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections • IFNA1

Efficacy and Safety of Clesrovimab (MK-1654) in Infants (MK-1654-004) (clinicaltrials.gov) - P2/3 | N=3632 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2/3

Phase classification • Trial completion • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections

Clesrovimab (MK-1654) in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease (MK-1654-007) (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Infectious Disease • Respiratory Diseases • Respiratory Syncytial Virus Infections