Clesrovimab RSV Monoclonal Antibody Clinical Trials, Dosage, Indication, Side Effects

Merck's Clesrovimab (MK-1654) is an investigational, extended half-life monoclonal antibody (mAb) developed as a passive immunization to prevent Respiratory syncytial virus (RSV). Clesrovimab is designed to be administered as the same 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. Merck says there is a high unmet need for preventative options in healthy and high-risk infants. 

Merck is known as MSD outside of the United States and Canada. For more information, visit www.merck.com.

U.S. CDC ACIP Clesrovimab Presentation

Anushua Sinha, MD, MPH Clinical Director -Vaccines Clinical Research 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 an Introduction, Evidence to Recommendations, and Clinical Consideration discussions.

U.S. FDA Clesrovimab

The U.S. Food and Drug Administration (FDA) accepted the Biologics License Application for clesrovimab (MK-1654) on December 17, 2024. The FDA has set a Prescription Drug User Fee Action date of June 10, 2025.

Clesrovimab Indication

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. 

Clesrovimab 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.

Long-acting Monoclonal Antibody Effectiveness

The administration of a long-acting monoclonal antibody reduced the risk of hospitalization for an RSV infection by around 80% in children under 6 months. 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.

Clesrovimab News

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 Phase 2b/3 Trial of Clesrovimab announced.

Clesrovimab Clinical Trials

MK-1654-004 (NCT04767373) is a Phase 2b/3 double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of clesrovimab in healthy preterm and full-term infants from birth to 1 year of age entering their first RSV season. The study enrolled 3,632 participants who were randomized 2:1 to receive either a single fixed dose of clesrovimab (105 mg intramuscular injection (IM)) or placebo on Day 1. Primary endpoints included the incidence of participants with RSV-associated medically attended lower respiratory infection (MALRI) from Day 1 (postdose) to Day 150 compared to placebo and safety. The MALRI definition required ≥1 indicator of LRI or severity. RSV-associated hospitalization through Day 150 and MALRI requiring ≥1 indicator of LRI or severity to Day 180 were prespecified secondary endpoints. Prespecified tertiary endpoints included acute respiratory infection, RSV-associated lower respiratory infection hospitalizations, and incidence of severe MALRI through Day 150. A post hoc analysis assessed more severe forms of RSV-associated MALRI (≥2 indicators of LRI and severity). Across endpoints, additional measures of efficacy were evaluated by Day 180. Safety measures included the percentage of participants with solicited injection-related adverse events (AEs), AEs of special interest (AESIs) solicited systemic AEs or serious adverse events (SAEs).

MK-1654-007 (NCT04938830) is a Phase 3, multicenter, randomized, partially blinded, controlled study to evaluate the safety, efficacy, and pharmacokinetics of clesrovimab in infants and children at increased risk for severe RSV disease compared to palivizumab. The study enrolled participants who were entering their first RSV season and recommended to receive palivizumab due to prematurity (≤35 weeks gestational age), chronic lung disease (CLD) of prematurity, or hemodynamically significant congenital heart disease (CHD). Participants were randomized 1:1 to receive clesrovimab (105 mg IM on Day 1, placebo on Day 28) or monthly palivizumab in their first season, and eligible participants received clesrovimab (210 mg IM) in the second RSV season. In this interim analysis, 901 participants were enrolled in the trial. The primary endpoint is the safety and tolerability of clesrovimab versus palivizumab in the first season. Secondary endpoints include the incidence of RSV-associated medically attended lower respiratory infections (MALRI) requiring ≥1 indicator of LRI or severity and RSV-associated hospitalization through Day 150.