Clesrovimab

The FDA is examining shots that protect infants from respiratory syncytial virus (RSV), according to a report from Reuters. The FDA is examining the safety of shots that protect infants from respiratory syncytial virus (RSV), according to a report from Reuters.The agency has notified executives at AstraZeneca, Merck and Sanofi that it is launching an investigation of their U.S.-approved RSV products, the news outlet reports, citing multiple sources.A spokesperson from Merck confirmed that it met with the FDA last week concerning the safety of its shot Enflonsia, which the agency just endorsed in June.AstraZeneca and Sanofi partner on blockbuster Beyfortus, which was approved in the U.S. in 2023. Beyfortus and Enflonsia are recommended for infants 8 months and younger heading into their first RSV season.“We welcome ongoing scientific exchange and dialogue with the FDA and other regulatory or health authorities, their advisory committees, and scientific leaders on Enflonsia, including its safety profile,” Merck’s spokesperson wrote via email. “We expect questions from the FDA, and we want them to ask. We believe deeply in the importance of transparency and we value the FDA’s rigorous review of our clinical data of all of our products—both on safety and efficacy.”Neither Enflonsia or Beyfortus are traditional vaccines. Both instead are long-acting monoclonal antibodies.“The evidentiary bar for establishing the safety of vaccines and preventive mAbs like Enflonsia is exceptionally, and appropriately, high,” Merck added.The scrutiny of RSV shots comes as U.S. health officials are questioning the safety of many other approved vaccines under the watch of Health and Human Services Secretary Robert F. Kennedy Jr., who is a long-time anti-vaccine activist.A few days ago, the head of the FDA’s Center for Biologics Evaluation and Research (CBER), Vinay Prasad, M.D., sent an internal email informing staffers that the agency was prepared to “acknowledge that COVID-19 vaccines have killed American children,” and that it was taking steps to tighten its regulations for vaccines.On Friday, the FDA’s revamped Advisory Committee on Immunization Practices (ACIP) voted to upend a longstanding CDC recommendation on the universal hepatitis B vaccination of newborns. The new stance—which leaves it up to parents to decide if they want their baby immunized—changes previous guidance that all babies receive a dose of the HBV vaccine within 24 hours of birth. Since the CDC made its initial recommendation in 1991, reported HBV infections among adolescents have dropped by 99%.The backlash against the FDA’s push to overhaul vaccine regulations has been loud. After Prasad’s declaration, a dozen former agency chiefs unanimously bashed the effort.“The proposed guidelines would dramatically change vaccine regulation on the basis of a reinterpretation of selective evidence and by a process that breaks sharply with the norms that have anchored the FDA’s globally respected scientific integrity,” the former commissioners wrote in a Dec. 3 article in The New England Journal of Medicine. As for RSV shots, former Center for Drug Evaluation and Research (CDER) director George Tidmarsh orchestrated a second look at Enflonsia in August, just two months after the FDA signed off on the Merck preventative, Reuters said, citing its review of internal documents.An AZ spokesperson said that it was deferring to Sanofi because it is the license holder of Beyfortus in the U.S.The safety and effectiveness of Beyfortus (nirsevimab) has been demonstrated in over 50 clinical studies and real-world studies, involving more than 400,000 infants. The largest real-world study of Beyfortus showed it reduced hospital and doctor visits for RSV disease in babies by 87%," Sanofi said. "At this time, no safety issue has been identified from clinical studies of nirsevimab or from post-marketing experience with more than six million babies immunized worldwide, while preventing an estimated 70,000 hospitalizations and emergency room visits in the US alone. All of this continues to show the benefits of Beyfortus in preventing severe RSV. "The anti-vaccine movement has already damaged public trust in the shots and taken a toll on sales in the U.S. In the third quarter, Sanofi reported that Beyfortus sales were up 20% worldwide year-over-year despite a 21% decline in the U.S. As for its vaccine sales overall, Sanofi sustained an 8% decline, with Chief Financial Officer François Roger noting a “negative buzz” around the jabs. GSK managed to squeak out a 2% overall increase in vaccine revenue despite a 15% decline of sales in the U.S., which the company chalked up largely to plummeting demand for its shingles jab Shingrix.Pfizer’s numbers (PDF) were particularly indicative of the erosion in demand for immunizations in the U.S. While sales of its Prevnar franchise of pneumococcal vaccines were up 18% year over year outside of the U.S., they were down 12% in the U.S. The same was true of COVID shot Comirnaty, which saw a 9% sales increase internationally and a 25% decline domestically.

Regulatory decisions once thought settled on protecting infants from respiratory syncytial virus (RSV) are now coming under renewed scrutiny, as the US Health and Human Services (HHS) department under Robert F. Kennedy Jr. pursues its broader rethink of childhood immunisation policy.A spokesperson for HHS confirmed to FirstWord that the FDA's Center for Drug Evaluation and Research (CDER), under newly appointed director Tracy Beth Høeg, is "rigorously reviewing the available data" for RSV therapies such as Sanofi and AstraZeneca's Beyfortus (nirsevimab-alip) and Merck & Co.'s newer Enflonsia (clesrovimab-cfor), both long-acting monoclonal antibodies aimed at protecting young children during their first RSV season."FDA routinely evaluates emerging safety information and will update product labeling if warranted by the totality of the evidence," said HHS press secretary Emily Hilliard in an emailed statement. "CDER's team is rigorously reviewing the available data, as it does for all products, to ensure decisions remain rooted in evidence-based science."Meeting with executivesThe news was first reported Tuesday in Reuters, citing people familiar with the matter who said US health officials had informed executives from the three companies last week that their RSV products would face additional regulatory scrutiny.The report indicates the review traces back several months, when FDA officials appointed under Kennedy – including Høeg, prior to being named CDER director – began quietly pressing for closer examination, starting as early as June.Last week, at a meeting of the CDC's Advisory Committee on Immunization Practices, during which the group dropped a decades-old hepatitis B vaccine guidance for newborns, Høeg pointed to what she described as an "unfavourable imbalance in all-cause mortality" observed across four late-stage RSV trials. In a presentation, she highlighted a slide showing five mortality events each in the Beyfortus arms of the MELODY and MEDLEY trials, and seven and eight, respectively, in the CLEVER and SMART trials of Enflonsia; there were 0, 1, 3 and 4 events, respectively, in the control groups of the trials, according to Høeg's presentation at ACIP.She said the finding was "not quite statistically significant, but yet this is very concerning to see in all four randomised trials, to see that there's actually a higher death rate, and so I think that this is something that could also be revisited by ACIP."A spokesperson for Merck, who confirmed to FirstWord that the company met briefly with FDA representatives last week, said "no deaths [in the CLEVER or SMART trials] were considered by the study investigators to be related to study intervention; no pattern was identified with respect to cause of death or time of death relative to intervention; and deaths were largely attributable to underlying co-morbidities or other identifiable causes."Beyfortus attained blockbuster status in its first full year on the market, with Sanofi reporting sales reaching €1.7 billion ($1.8 billion) in 2024, while Merck expects Enflonsia, which was only approved this past June, to generate about $250 million in sales in 2026, according to the Reuters report. Both are included in the CDC's recommended childhood immunisation schedule.Real-world analysesAn analysis by the CDC earlier this year looked at RSV-associated hospitalisations after the introduction of RSV prevention products. When researchers compared RSV hospitalisations in infants under eight months old during the 2024-25 season with rates seen before the COVID-19 pandemic in two surveillance networks, they found hospital admissions were about 28% and 43% lower.Sanofi boasts even stronger outcomes, citing a real-world study of Beyfortus showing an 87% reduction in RSV-related hospital and doctor visits among immunised infants."At this time, no safety issue has been identified from clinical studies of [Beyfortus] or from post-marketing experience with more than 6 million babies immunised worldwide," a Sanofi spokesperson told FirstWord. "We have extensive safety monitoring processes in place across all our products throughout the entire product lifecycle…Any adverse event case that is reported to Sanofi following the use of our product is tracked in a global safety database, assessed to determine whether the adverse event is related to the product or not, and immediately submitted to FDA and other relevant health authorities. We conduct ongoing safety monitoring not only on an individual case report, but also on aggregated data to investigate any trends in reporting."