The FDA has approved Merck’s Enflonsia (clesrovimab-cfor), a long-acting monoclonal antibody, for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in infants born during or entering their first RSV season.
The once-per-season injection offers a new option to safeguard infants from RSV-related illness, a major cause of pediatric hospitalizations in the US.
Enflonsia is administered as a single 105 mg intramuscular injection and does not require weight-based dosing.
The recommendation is for Enflonsia to be administered at birth for infants born during the RSV season. For those born outside the season, it should be given just before their first RSV season begins.
Enflonsia is now the second such product approved for RSV prevention in infants, following the approval of Sanofi and AstraZeneca’s Beyfortus (nirsevimab) in 2023.
Compared to Beyfortus, Enflonsia offers some logistical advantages, most notably its fixed, single-dose regimen that doesn’t depend on infant weight, unlike Beyfortus, which requires two dosing options based on weight.
Enflonsia is a preventive monoclonal antibody designed to deliver rapid, consistent and lasting protection throughout a typical five-month RSV season, which typically begins in November and runs through to March.
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In the US, approximately 58,000 children under the age of five are hospitalized each year due to RSV infections, resulting in an estimated 100 to 500 deaths annually in this age group. Worldwide, RSV leads to the hospitalization of around 3 million children under five each year and causes roughly 100,000 deaths annually.
In low- and middle-income countries, RSV ranks as the second-leading cause of death in young children, following malaria.
Although RSV symptoms often resemble those of a severe cold, the virus can be life-threatening for infants, older adults and individuals with weakened immune systems.
Enflonsia’s approval was based on data from two pivotal trials: the CLEVER trial and the SMART trial. In the Phase IIb/III CLEVER trial, which enrolled over 3,600 healthy infants,
Enflonsia reduced the incidence of medically attended RSV lower respiratory tract infections (MALRI) by 60.5% over a five-month period compared to placebo. It also demonstrated an 84.3% reduction in RSV-related hospitalizations.
In the SMART trial, which focused on high-risk infants, such as those born extremely preterm or with chronic lung or heart disease, Enflonsia showed efficacy and safety comparable to Synagis (palivizumab), the previous standard of care.
Enflonsia’s safety profile was consistent with other monoclonal antibodies used in pediatrics.
“RSV disease is the leading cause of infant hospitalization in the US and can lead to serious respiratory conditions like bronchiolitis and pneumonia,” said Dr. Octavio Ramilo, chair of the Department of Infectious Diseases at St. Jude Children’s Research Hospital and investigator for the CLEVER and SMART trials, in a press release announcing the approval.
“Enflonsia combines dosing convenience with strong clinical data showing significant reductions in RSV disease incidence and hospitalizations, making it a promising new intervention to help protect infants from RSV.”
Related: Clesrovimab Shows Promise for RSV in Infants
Enflonsia Joins RSV Prevention Market as Sanofi Ramps Up Supply for Upcoming RSV Season
The approval adds to a growing arsenal of RSV prevention tools, including maternal vaccines like GSK’s Arexvy (also approved for older individuals) and Pfizer’s Abrysvo (approved for adults and older individuals as well), and other monoclonal antibodies such as Beyfortus.
Beyfortus has remained the only RSV prophylactic on the market until now, although Abrysvo can also be administered to women during weeks 32 to 36 of their pregnancies to protect newborns.
As the lone monoclonal RSV drug on the market, Beyfortus has been facing supply challenges, with reports indicating that demand for Beyfortus exceeded initial supply. The treatment reached sales of €1.7 billion ($1.8 billion) in 2024.
On the same day of Enflosia’s approval, Sanofi announced it has begun shipping Beyfortus globally starting in early Q3 to ensure healthcare providers have ample supply ahead of the 2025 to 2026 RSV season. The company said it has tripled production capacity and doubled manufacturing sites since 2023, with current supply already matching the total doses distributed last season.
Due to differences in their respective clinical trials, direct comparisons between Enflonsia and Beyfortus are difficult to make. Although both are monoclonal antibodies, they target distinct antigenic sites.
In addition to its single-dose, weight-independent administration, Merck has suggested that RSV may be more prone to developing resistance to the Sanofi and AstraZeneca product.
On the other hand, Sanofi has highlighted Beyfortus’ 75% reduction in MALRI, compared to Enflonsia’s 60%. The company also notes that Beyfortus now carries an updated European label reflecting six months of protection, which it sees as a key differentiator.
The CDC’s Advisory Committee on Immunization Practices (ACIP) is expected to review and discuss recommendations for Enflonsia’s use at the end of June.
Merck plans to begin shipping Enflonsia ahead of the 2025 to 2026 RSV season, with ordering expected to start in July.
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