Phase III Trial Data Leads to FDA Priority Review of sBLA for Expanded Indication of Arexvy for RSV

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The FDA has granted Priority Review designation to GSK’s supplemental Biologics License Application (sBLA) to expand the indication of the adjuvanted respiratory syncytial virus (RSV) vaccine Arexvy to include adults 50-59 years of age with an increased risk for the virus. The FDA assigned the application with a Prescription Drug User Fee Act action date of June 7, 2024.¹

Arexvy contains a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) combined with GSK’s proprietary AS01_E adjuvant. The sBLA filing was based on positive data from a Phase III trial (NCT05590403) that analyzed the immune response and safety of Arexvy in individuals 50-59 years of age, which included participants with an elevated risk of RSV-related lower respiratory tract disease (LRTD) from underlying medical conditions.

Trial NCT05590403 evaluated the immune response produced by Arexvy in this population with pre-defined stable chronic diseases that elevate their risk of RSV disease to compare with a broader group without pre-defined chronic diseases as well as adults aged 60 years and older. The primary endpoints of the study were RSV-A and RSV-B neutralization titers for both cohorts of those 50 to 59 years of age at one month post immunization and compared with those aged 60 years and older. The results of the trial are set to be presented at upcoming medical conferences and submitted for peer-reviewed publication, in addition to other regulatory submissions that will support potential label expansions.¹

RSV develops in 3% to 7% of healthy older adults in the United States and Europe annually, with an estimated 177,000 hospitalizations and 14,000 deaths each year in the United States alone. RSV can be especially severe in older adults, as approximately 18% of hospitalizations involve admission to an intensive care unit; 31% of individuals receive home health services at discharge; and 26% die within one year post admission. Among older adults, RSV is a common cause of LRTD, which affects the lungs and can cause life-threatening pneumonia and bronchiolitis. The CDC has found that RSV leads to approximately 60,000-120,000 annual hospitalizations and 6,000-10,000 annual deaths among adults 65 years of age and older.²

In May 2023, Arexvy became the first FDA-approved RSV vaccine to prevent LRTD caused by RSV in individuals 60 years of age and older.²

“Older adults, in particular those with underlying health conditions, such as heart or lung disease or weakened immune systems, are at high risk for severe disease caused by RSV,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a press release announcing the approval. “[The] approval of the first RSV vaccine is an important public health achievement to prevent a disease which can be life-threatening and reflects the FDA’s continued commitment to facilitating the development of safe and effective vaccines for use in the United States.”²

The FDA based the approval on data from a trial that included approximately 12,500 participants administered Arexvy and 12,500 participants administered placebo. Arexvy was found to reduce the risk of developing RSV-associated LRTD by 82.6% and lowered the risk of developing severe RSV-associated LRTD by 94.1%.

The efficacy of Arexvy was 94.6% among older adults with at least one underlying medical condition of interest, including certain cardiorespiratory and endocrine-metabolic conditions. Efficacy against severe RSV-LRTD, defined as an RSV-associated LRTD episode that inhibited normal, everyday activities, was 94.1%.³

The most common adverse events in those administered Arexvy were injection site pain, fatigue, muscle pain, headache, and joint stiffness/pain. Among all clinical trial participants, atrial fibrillation within 30 days of vaccination was reported in ten individuals who received Arexvy and four individuals who received the placebo.

In June 2023, the CDC Advisory Committee on Immunization Practices voted to recommend Arexvy for individuals 60 years of age and older using shared clinical decision making. This involves patients working on an individual level with their health care providers to determine whether RSV vaccination is appropriate.⁴

References

1. GSK’s RSV vaccine, Arexvy, accepted under Priority Review in US for the prevention of RSV disease in adults aged 50-59 at increased risk. GSK. News release. February 6, 2024. Accessed February 6, 2024. https://www.gsk.com/en-gb/media/press-releases/arexvy-accepted-under-priority-review-in-us-for-the-prevention-of-rsv-disease-in-adults-aged-50-59-at-increased-risk/

2. FDA Approves First Respiratory Syncytial Virus (RSV) Vaccine. FDA. News release. May 3, 2023. Accessed February 6, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-respiratory-syncytial-virus-rsv-vaccine?utm_medium=email&utm_source=govdelivery.

3. US FDA approves GSK’s Arexvy, the world’s first respiratory syncytial virus (RSV) vaccine for older adults. GSK. News release. May 3, 2023. Accessed February 6, 2024. https://www.gsk.com/en-gb/media/press-releases/us-fda-approves-gsk-s-arexvy-the-world-s-first-respiratory-syncytial-virus-rsv-vaccine-for-older-adults.

4. US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices votes to recommend Arexvy for the prevention of RSV disease in adults aged 60 and older with shared clinical decision making. GSK. News release. June 22, 2023. Accessed February 6, 2024. https://www.gsk.com/en-gb/media/press-releases/cdc-and-prevention-acip-votes-to-recommend-arexvy/