Efficacy And Safety Of Bivalent Respiratory Syncytial Virus (RSVpreF) Vaccine In Older Adults

ABSTRACT

Background. Respiratory syncytial virus (RSV) is an important cause of disease in older adults and is associated with high morbidity and mortality, especially in those with high-risk conditions. Illness can vary from mild upper respiratory tract symptoms to more severe lower respiratory tract disease. After over 50 years of research, there is now hope for an RSV vaccine for any population, including older adults. An investigational bivalent RSV A and B, stabilized RSV prefusion F subunit vaccine (RSVpreF) was assessed successfully in a pivotal phase 3 efficacy study in older adults. (NCT05035212). Methods. The primary efficacy objective of this Phase 3, global, multicenter, randomized, double-blinded, placebo-controlled study was to evaluate the prevention of RSV associated lower respiratory tract illness (LRTI-RSV) in up to 40,000 adults >=60 years of age during the first winter season (September 2021-June 2022). Two primary endpoints were tested sequentially - LRTI-RSV with >=2 and >=3 symptoms. A pre-planned efficacy interim analysis (IA) was to be conducted by an external Data Monitoring Committee (DMC) upon accrual of at least 29 cases of LRTI-RSV with >=2 symptoms. With efficacy demonstrated for cases with >=2 symptoms and sufficient cases with >= 3 symptoms accrued, an efficacy analysis of cases with >= 3 symptoms was to be conducted. The ongoing study is collecting additional safety and descriptive efficacy data. Results. At the time of the IA, approximately 34,000 participants received either RSVpreF 120 mug (60 mug each of RSVpreF from RSV A and RSV B) or placebo (11 randomization). Forty-four LRTI-RSV cases with >=2 symptoms were accrued with 11 cases in the RSVpreF group and 33 cases in the placebo group corresponding to a VE of 66.7% (96.66% CI 28.8%, 85.8%). Sixteen LRTI-RSV cases with >=3 symptoms were accrued with 2 cases in the RSVpreF group and 14 cases in the placebo group corresponding to a VE of 85.7% (96.66% CI 32.0%, 98.7%). The investigational vaccine was well-tolerated with no safety concerns. Conclusion. Despite unpredictable RSV activity due to the COVID-19 pandemic, the primary objective of the study was met demonstrating that RSVpreF had a favorable safety profile and was highly efficacious in preventing LRTI-RSV with >=2 symptoms and >=3 symptoms in older adults 60 years and older.