Merck’s RSV shot for infants shows promise, could be available in 2025
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Key takeaways:
- Clesrovimab was 91% effective at preventing medically attended lower respiratory tract infections vs. placebo.
- One dose of clesrovimab performed similarly to five doses of palivizumab among high-risk infants.
Another monoclonal antibody for preventing respiratory syncytial virus disease in infants could enter the market as early as next year, based on the results of two studies presented at IDWeek, Merck said.
The United States already has multiple tools to prevent severe RSV in infants, including Sanofi’s monoclonal antibody (mAb), nirsevimab, and a maternal vaccine from Pfizer. The next product coming down the pipeline could be Merck’s mAb clesrovimab.
Investigators presented the results of two studies that tested the safety and efficacy of clesrovimab among healthy infants and children at risk for severe RSV infection.
“Clesrovimab is directed against the site IV of the RSV F protein, and site IV is present in both the prefusion and postfusion conformation,” Octavio Ramilo, MD, chair of infectious diseases at St. Jude’s Children’s Research Hospital in Memphis, Tennessee, told Healio. “It is a little bit different than the site 0 of nirsevimab that is only present in the prefusion form.”
Ramilo explained that clesrovimab protects against RSV subtypes A and B, and in adult trials, the mAb concentrated well in participants’ respiratory mucosa.
Clesrovimab vs. placebo
In a phase 2b/3 trial, Ramilo and colleagues randomly assigned 2,411 infants (50.9% boys; median age, 3 months) to receive one 105 mg dose of clesrovimab and 1,203 infants (51.3% boys; median age, 3.1 months) to receive placebo. About 17% of the infants were born between 29- and 35-weeks’ gestation; the rest were born at 35 weeks’ gestation or later. The researchers recruited participants from 22 countries.
“We did what we call active surveillance,” Ramilo said. “Instead of waiting for the families to tell us that their kid was sick, we called them every week, and [if] the kids had symptoms or a runny nose, we brought them in, and we tested them for RSV.”
After 6 months, the researchers found that clesrovimab was 50% (95% CI, 37.4%-60.1%) effective at preventing acute respiratory infections compared with placebo, 81.3% (95% CI, 62.6%-90.7%) effective at preventing hospitalization, and 91.7% (95% CI, 62.9%-98.1%) effective at preventing severe medically attended lower respiratory tract infections (MALRI).
Clesrovimab vs. palivizumab
Ramilo and colleagues also conducted a phase 3 partially blinded randomized trial comparing clesrovimab with palivizumab — another available mAb — among children who were at risk for more severe RSV infection.
They randomly assigned 446 infants (50.4% boys; mean age, 3 months) to receive one 105 mg dose of clesrovimab, followed by one dose of placebo 1 month later. Another 450 infants (49.1% boys; mean age, 3 months) were assigned to receive five doses of palivizumab in monthly intervals during their first respiratory season. The researchers recruited infants from 27 countries who were born prematurely, had chronic lung disease or had congenital heart disease.
“After day 60, it was unblinded,” Ramilo said. “The kids who were in the palivizumab arm kept getting palivizumab ... but the kids on clesrovimab, we decided not to give any more shots.”
Within 150 days of receiving their first dose, 14 infants in the clesrovimab group experienced MALRI (incidence rate [IR] = 3.6%; 95% CI, 2%-6%), and five infants were hospitalized (IR = 1.3%; 95% CI, 0.4%-3%). In the palivizumab group, 12 infants had MALRI (IR= 3%; 95% CI, 1.6%-5.3%), and six infants were hospitalized (IR = 1.5%; 95% CI, 0.6%-3.3%).
“One dose of clesrovimab was sufficient to prevent severe RSV disease in these high-risk youth [compared with] five doses of palivizumab in year one,” Ramilo said.
The researchers reported 120 drug-related adverse events and 99 serious adverse events in the clesrovimab group vs. 127 drug-related adverse events and 110 serious adverse events in the palivizumab group. Eight infants in the clesrovimab group and four in the palivizumab group died, but the researchers said the deaths were not related to the study.
Because this group of infants were at risk for serious RSV disease, Ramilo said they extended the trial into a second RSV season. There were 60 children from the clesrovimab group and 57 from the palivizumab group who all received one 210 mg dose of clesrovimab. This part of the study is ongoing, Ramilo said.
Next steps
Ramilo is interested in seeing if preventing RSV in infants could have long-term benefits beyond their first year of life. He also wants to see if clesrovimab is safe for immunocompromised children.
“Working at St. Jude’s with a high population of kids that have severely compromised immune systems because of cancer therapy, transplant or other immunodeficiencies, we will be very interested in exploring that as well,” Ramilo said.
Paula Annunziato, MD, senior vice president of infectious diseases and vaccines for Merck’s Global Clinical Development, told Healio that the company will include results from both trials in regulatory submissions in the U.S. and other countries.
“We are working expeditiously with regulators to put into place a global filing strategy to help address unmet need for RSV prevention worldwide,” Annunziato said. “Based on our current plans, if approved, we anticipate clesrovimab will be available with the goal of helping address RSV burden during the 2025-2026 RSV season.”
Ramilo is excited about having another option to protect infants from severe RSV infection, but said pediatricians need to educate parents about these tools.
“In Europe, they have done a much better job in introducing these preventive studies than we are doing in the U.S.,” Ramilo said. “We need to catch up and make sure that ... between the maternal vaccination and the monoclonals, we can reach as many families and children as we can.”
References:
- 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. https://www.merck.com/news/mercks-clesrovimab-mk-1654-an-investigational-respiratory-syncytial-virus-rsv-preventative-monoclonal-antibody-significantly-reduced-incidence-of-rsv-disease-and-hospitalization-in-heal/. Published Oct. 17, 2024. Accessed Oct. 18, 2024.
- Zar HJ, et al. Abstract 166. Presented at: IDWeek; Oct. 16-19, 2024; Los Angeles.
- Zar HJ, et al. Abstract 167. Presented at: IDWeek; Oct. 16-19, 2024; Los Angeles.
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Zar HJ, et al. Abstract 166. Presented at: IDWeek; Oct. 16-19, 2024; Los Angeles.
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