AREXVY™ RSVPreF3 OA RSV Vaccine March 2023
GSK's AREXVY™ RSV OA (Older Adult) monovalent RSV vaccine candidate contains a recombinant subunit pre-fusion respiratory syncytial virus (RSV) glycoprotein antigen (RSVPreF3) combined with GSK's proprietary AS01 adjuvant. The antigen plus adjuvant combination may help overcome the natural decline in immunity that contributes to the challenge of protecting people from RSV disease.
AREXVY contains Agenus' proprietary QS-21 STIMULON™ within its AS01 adjuvant, which has already demonstrated positive immune responses and a favorable safety profile. QS-21 Stimulon improves a vaccine's effectiveness by inducing strong antibody and cell-mediated immune responses. It also plays a key role in boosting immune response in older adults who often experience age-related decline in immunity.
GSK announced positive phase III trial results for its RSV vaccine candidate for adults aged rs and above to be presented at IDWeek 2022. The vaccine candidate was highly efficacious, demonstrating overall vaccine efficacy of 82.6% (96.95% CI, 57.9–94.1, 7 of 12,466 vs. 40 of 12,494) against RSV lower respiratory tract disease (RSV-LRTD), meeting the AReSVi 006's primary endpoint.
On February 16, 2023, the NEJM published an ORIGINAL ARTICLE: Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. Findings: A single dose of the RSVPreF3 OA vaccine had an acceptable safety profile in a phase 3 study and prevented RSV-related acute respiratory infection and lower respiratory tract disease and severe RSV-related lower respiratory tract disease in adults 60 years of age or older, regardless of RSV subtype and the presence of underlying coexisting condition GlaxoSmithKline Biologicals funded the study; AReSVi-006 ClinicalTrials.gov number, NCT04886596.
GlaxoSmithKline plc (LSE/NYSE: GSK) is a science-led global healthcare company. For further information, please visit www.gsk.com/about-us. AREXVY trademark was issued on November 15, 2022.
AREXVY U.S. CDC Review
The U.S. CDC Advisory Committee on Immunization Practices (ACIP) conducted an AREXVY review on February 23, 2023; presentations included Ismael R. Ortega-Sanchez, Ph.D., presented - Economics of Vaccinating U.S. Adults ≥60 years old against RSV; Evidence to Recommendations Framework.
On October 20, 2022, Bishoy Rizkalla, GSK Global Medical Affairs, presented an update to the CDC's vaccine committee.
AREXVY U.S. FDA Review
The U.S. Food and Drug Administration (FDA) scheduled a Vaccines and Related Biological Products Advisory Committee (VRBPAC) AREXVY review meeting for (STN 125775/0) on March 1, 2023. The FDA published: Briefing Document; GSK SPONSOR BRIEFING DOCUMENT, Errata to the GSK Briefing Document. Committee voted unanimously (100%) that the data support the effectiveness of the vaccine and 10-2 that the data support the safety of the RSV vaccine.
On November 2, 2022, GSK announced that the U.S. FDA had accepted a Biologics License Application (BLA) (STN 125775/0) and granted a Priority Review for their RSVPreF3 OA vaccine candidate. The FDA action date for their regulatory decision is May 3, 2023.
AREXVY Availability March 2023
GSK plc stated announcements on regulatory progress in Australia, Japan, the U.S., and E.U. are expected in 2023.
AREXVY Indication
According to the WHO, RSV represents a significant health threat for older adults (>65 years of age), with 360,000 hospitalizations and 24,000 deaths associated with RSV infections estimated annually in developed countries. In addition, the risk of severe disease in adults is increased by underlying chronic pulmonary disease, circulatory conditions, and functional disability and is associated with higher viral loads.
AREXVY Coadministration Influenza Vaccines
GSK presented to the U.S. FDA acceptable coadministration with influenza vaccine data on March 1, 2023.
AREXVY Dosage
Recent in-house results from a parallel phase III trial, AReSVi 004, showed that, in participants aged 60 years and above, one dose of the RSV OA investigational vaccine induced strong humoral and cellular immune responses, which remain above pre-vaccination levels up to at least the six months post-vaccination readout timepoint.
AREXVY Safety Data
GSK presented data to the U.S. FDA on March 1, 2023, indicating limited serious safety data following vaccination in multiple studies.
AREXVY Maternal Vaccine Candidate
The maternal RSV candidate vaccine was tested in three doses compared with a placebo in 502 healthy non-pregnant women over monthly visits (Day 8, Day 31, and Day 91 post-immunization). The data show that compared with the base, the investigational vaccine rapidly boosted the pre-existing immunity at all dose levels, leading to high levels of protective neutralizing antibodies; On Day 8, a 14-fold increase in RSV-A and RSV-B neutralizing antibody titers was observed.
AREXVY News 2023
March 1, 2023 - Phil Dormitzer, Global Head of Vaccines R&D, GSK, commented in a press release, "Today's vote brings us an important step closer to delivering one of the world's first vaccines for RSV..... We're delighted that the Advisory Committee recognized the strength of our vaccine's data and its potential to make a positive public health impact with a unanimous vote on the vaccine's effectiveness."
February 28, 2023 - The U.S. FDA scheduled a VRBPAC review meeting for GSK's AREXVY for March 1, 2023.
February 16, 2023 - The peer-review New England Journal of Medicine published an Original Article: Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults.
November 2, 2022 - The U.S. FDA has set a Prescription Drug User Fee Act action date of May 3, 2023. If approved, GSK's RSV older adult vaccine candidate has the potential to be the first vaccine available to help protect adults aged 60 years and older from lower respiratory tract disease caused by RSV infection.
October 21, 2022 - GSK plc announced that a new drug application for its RSV older adult vaccine candidate (RSVPreF3 OA) had been accepted for review by the Japanese Ministry of Health, Labour, and Welfare.
October 13, 2022 - GSK's older adult RSV vaccine candidate shows a 94.1% reduction in severe RSV disease and overall vaccine efficacy of 82.6% in the pivotal trial.
June 10, 2022 - GSK plc announced positive headline results from a pre-specified efficacy interim analysis of the AReSVi 006 phase III trial. The interim analysis indicates the primary endpoint was exceeded, with no unexpected safety concerns observed.
June 10, 2022 - Agenus shared that partner GSK announced positive headline results from a pre-specified efficacy interim analysis of the AReSVi 006 phase III trial evaluating their investigational RSV vaccine in adults aged 60 years and above. The primary endpoint was exceeded, with no unexpected safety concerns observed.
February 16, 2021 - GSK announced the Phase 3 RSV candidate program for older adults. This phase 3 study is after the release of positive Phase I/II results on safety, reactogenicity, and immunogenicity.
November 23, 2020 - GlaxoSmithKline plc announced that patient dosing had begun in phase 3 clinical program investigating the safety and efficacy of its RSV candidate vaccine for maternal immunization (GSK3888550A) following the presentation of positive phase 1/2 safety, reactogenicity, and immunogenicity data last month
RSV OA Vaccine Clinical Trials
The GSK RSVPreF3 RSV vaccine has been involved in over ten clinical studies.
The AReSVi-006 (Adult Respiratory Syncytial Virus) phase III trial is a randomized, placebo-controlled, observer-blind, multi-country demonstrating the efficacy of a single dose of GSK's adjuvanted RSVPreF3 OA investigational vaccine in adults aged 60 years and above. Approximately 25,000 participants were enrolled from 17 countries. AReSVi 006 is a phase III trial. Last Update Posted: June 30, 2022.
RESULTS: A total of 24,966 participants received one dose of the RSVPreF3 OA vaccine (12,467 participants) or placebo (12,499). Over a median follow-up of 6.7 months, vaccine efficacy against RT-PCR–confirmed RSV-related lower respiratory tract disease was 82.6% (96.95% confidence interval [CI], 57.9 to 94.1), with 7 cases (1.0 per 1000 participant-years) in the vaccine group and 40 cases (5.8 per 1000 participant-years) in the placebo group. Vaccine efficacy was 94.1% (95% CI, 62.4 to 99.9) against severe RSV-related lower respiratory tract disease (assessed based on clinical signs or by the investigator) and 71.7% (95% CI, 56.2 to 82.3) against RSV-related acute respiratory infection. Vaccine efficacy was similar against the RSV A and B subtypes (for RSV-related lower respiratory tract disease: 84.6% and 80.9%, respectively; for RSV-related acute respiratory infection: 71.9% and 70.6%, respectively). In addition, high vaccine efficacy was observed in various age groups in participants with coexisting conditions. The RSVPreF3 OA vaccine was more reactogenic than the han placebo, but most adverse events for which reports were solicited were transient, with mild-to-moderate severity. The incidences of serious adverse events and potential immune-mediated diseases were similar in the two groups.
