Merck’s investigational monoclonal antibody, Clesrovimab (MK-1654), has shown promising results in significantly reducing the incidence of respiratory syncytial virus (RSV) disease and related hospitalizations in healthy preterm and full-term infants. Findings presented at IDWeek 2024 highlight Clesrovimab’s potential as a crucial preventive measure for infants during their first RSV season.

In a Phase 2b/3 trial, Clesrovimab achieved a 60.4% reduction in RSV-associated medically attended lower respiratory infections (MALRI) compared to placebo over five months. Notably, RSV-associated hospitalizations were reduced by 84.2%, while hospitalizations due to RSV-associated lower respiratory infections declined by 90.9%. Severe cases of MALRI were reduced by 91.7%.

Anushua Sinha, MD, infectious disease physician and product development team lead at Merck, discussed this study, along with another Phase 3 study it was paired with, at IDWeek, “The first is Protocol 4, which is our Phase 2b/3 study. It is double-blinded, placebo-controlled, multi-center, and was conducted in over 22 countries. The safety and efficacy results of Clesrovimab demonstrated 84% efficacy against RSV hospitalization and over 90% efficacy against RSV lower respiratory infection hospitalization. This was coupled with a safety profile that showed its safety was generally comparable to that of placebo in the study, which is paired with the presentation from our study in high-risk infants.”

The double-blind, randomized, placebo-controlled trial, MK-1654-004, enrolled 3,632 infants aged from birth to one year, focusing on safety and efficacy. Adverse events were comparable between the Clesrovimab and placebo groups, with no treatment-related deaths reported. Interim data from the ongoing Phase 3 trial (MK-1654-007) comparing Clesrovimab with the standard treatment, Palivizumab, included 901 participants revealing comparable safety profiles and incidence rates of RSV-associated MALRI and hospitalizations between the two treatments.

Additionally, Sinha discussed this Phase 3 trial evaluating the safety and efficacy of Clesrovimab in infants at increased risk for severe RSV disease, including those with chronic lung disease or congenital heart disease. She explained, “Protocol 7, which is our Palivizumab-controlled study in high-risk infants, including babies with congenital lung disease or prematurity, and congenital heart disease. Safety was the primary endpoint in this study, and we demonstrated that Clesrovimab’s safety was generally comparable to that of the comparator Palivizumab used in that study. Moreover, we collected the pharmacokinetic data that will enable us to bridge the efficacy demonstrated in Protocol 4 for the healthy baby study. Taken together, this set of data supports the use of Clesrovimab in both healthy infants and high-risk infants for the prevention of RSV as they enter their first season.”

Sinha emphasized the practicality of Clesrovimab, stating, “Clesrovimab is administered in the same dose for all infants, regardless of their weight or whether they are born during the RSV season or outside of it. This simplification in how we deliver prevention provides significant convenience for busy pediatric and family practice offices, streamlining the workflow during a morning or afternoon session. This is an important enhancement for the seasonal care that doctors and nurses provide when administering RSV prevention for infants.” This could represent a major advancement in protecting infants from RSV, which is responsible for an estimated 101,000 deaths annually in children under five worldwide.

About RSV

“RSV is the most common cause of hospitalization for infants in our healthcare system. Until now, treating RSV has primarily focused on supportive care, which includes intravenous fluids for babies who are short of breath and unable to feed adequately, as well as supplemental oxygen for those who are hypoxemic and experiencing increased work of breathing. This situation fills our emergency rooms, doctor’s offices, and pediatric wards every winter,” Sinha explained.

In conclusion, Sinha noted, “Many doctors are already accustomed to providing RSV prevention for high-risk babies, who have had access to Palivizumab for many years. With Clesrovimab, the focus will expand beyond just high-risk infants to include all babies, recognizing that while high-risk infants are particularly vulnerable, all infants are at risk of RSV disease, especially during their first season when they are the smallest.”

Merck’s Clesrovimab presents a new approach to RSV prevention in infants, with clinical trial results supporting potential regulatory approval. The healthcare community looks forward to further developments in pediatric health.

References

1. Merck’s Clesrovimab (MK-1654), an Investigational Respiratory Syncytial Virus (RSV) Preventative Monoclonal Antibody, Significantly Reduced Incidence of RSV Disease and Hospitalization in Healthy Preterm and Full-term Infants. Merck. October 17, 2024. Accessed October 22, 2024. https://www.businesswire.com/news/home/20241017875997/en

2. A Phase 2b/3 Study to Evaluate the Efficacy and Safety of an Investigational Respiratory Syncytial Virus (RSV) Antibody, Clesrovimab, in Healthy Preterm and Full-Term Infants. Presentation #166 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.

3. Phase 3, Randomized, Controlled Trial Evaluating Safety, Efficacy, and Pharmacokinetics (PK) of Clesrovimab in Infants and Children at Increased Risk for Severe Respiratory Syncytial Virus (RSV) Disease. Presentation #167 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.