GSK: 3-Year Efficacy Data for Arexvy in Older Adults Published in Lancet Respiratory Medicine

A single dose of the AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA; Arexvy; GSK) demonstrated 62.9% efficacy against RSV-related lower respiratory tract disease (RSV-LRTD) over 3 consecutive seasons in adults aged 60 years and older, according to new research published in The Lancet Respiratory Medicine.

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The vaccine was effective against both RSV A (69.8%) and RSV B (58.6%) subtypes, though protection waned from 82.6% in season 1 to 48.0% in season 3. Notably, revaccination after one year showed no clear additional benefit over a single dose. The findings are from the phase 3 AReSVi-006 trial (NCT04886596), a randomized, observer-blind, placebo-controlled study across 275 centers in 17 countries.

The trial enrolled 24,972 adults aged 60 years and older between May 25, 2021, and January 31, 2022. Participants were initially assigned randomly 1:1 to receive either RSVPreF3 OA or placebo before the first RSV season. Prior to season 2, RSVPreF3 OA recipients were randomly re-assigned to receive either a second dose (RSV revaccination group) or placebo (RSV single-dose group). Placebo recipients from season 1 also received placebo before season 2, according to the study.

For the efficacy analyses, researchers included 12,468 RSVPreF3 OA recipients and 12,498 placebo recipients, with median follow-up from day 15 after the first dose of 30.6 months. The cumulative efficacy of a single RSVPreF3 OA dose over 3 seasons was 62.9% (97.5% CI 46.7–74.8) against RSV-LRTD, 69.8% (42.2–85.7) against RSV A-related LRTD, and 58.6% (35.9–74.1) against RSV B-related LRTD.

The investigators reported consistent efficacy across subpopulations evaluated for the study. The vaccine demonstrated efficacy in adults aged 60–69 years and 70–79 years (70.6%), pre-frail participants (walking speed 0.4–0.99 m/s), and individuals with pre-existing conditions that increase risk for severe RSV-LRTD (64.7–70.1% efficacy). The researchers noted that they were unable to reliably estimate efficacy in participants described as “fully frail” or those aged 80 years and older because of the insufficient number of cases.

Protection Remains Consistent

There was a clear decline in vaccine efficacy over the 3-year study period, according to the findings, measuring 82.6% in the first season, 67.2% in the second season, and 48.0% in the third season. Despite this decline, protection remained statistically significant through all 3 seasons. The group receiving a second dose 1 year following the initial vaccination showed a cumulative efficacy of 67.8%, which was comparable to that of the single-dose regimen with no clear additional benefit observed, according to the findings. Based on immunogenicity data, the researchers noted, neutralizing antibody levels decreased between seasons but remained above baseline before the third season.

The safety profile of RSVPreF3 OA was clinically acceptable throughout the study, authors wrote. Serious adverse events considered related to the intervention by investigators occurred in fewer than 1% of participants across all groups. Five deaths were assessed as intervention-related: 3 in the vaccine groups (cardiopulmonary failure, cardiac arrest, and left ventricular failure) and 2 in the placebo group (death of unknown cause and pulmonary embolism).

Respiratory syncytial virus (RSV) poses a significant health risk for adults 60 and older, especially those with chronic medical conditions like COPD, congestive heart failure, diabetes, or kidney failure. After 6 decades of research, RSV vaccines finally became available in 2023, with 3 formulations now approved for older adults. Arexvy is the first licensed RSV vaccine to demonstrate sustained protective efficacy across 3 consecutive RSV seasons in this vulnerable older population. More research will be needed to determine the best revaccination strategies to maintain immunity beyond this timeframe, authors wrote.

Source: Ison MG, Papi A, Athan E, et al. Efficacy, safety, and immunogenicity of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial. Lancet Respir Med. 2025. doi:10.1016/S2213-2600(25)00048-7