AREXVY™ RSV Vaccine August 2023
GlaxoSmithKline Biologicals (GSK) AREXVY™ recombinant, AS01E adjuvanted, single dose, RSV vaccine contains a recombinant subunit pre-fusion respiratory syncytial virus (RSV) glycoprotein antigen (RSVPreF3) combined with GSK's proprietary ASO1 adjuvant. The antigen plus adjuvant combination helps 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 crucial 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 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-LRTD in adults 60 years of age or older, regardless of RSV subtype and the presence of the underlying coexisting condition. GSK funded the AReSVi-006 ClinicalTrials.gov NCT04886596.
The European Medicines Agency (EMA) recommended marketing authorization in the European Union (EU) on April 26, 2023, for Arexvy for active immunization to protect adults aged 60 years and older against LRTD caused by RSV. The opinion of EMA's Committee for human medicines (CHMP) is based on data from a randomized, placebo-controlled trial in 25,000 adults in 17 countries. The results showed an estimated 83% protection against RSV-confirmed LRTD for at least six months. On May 3, 2023, the U.S. Food and Drug Administration (FDA) approved Arexvy to prevent LRVD caused by RSV in individuals 60 and older in the U.S. (PRESCRIBING INFORMATION, Package Insert). On June 22, 2023, Tony Wood, Chief Scientific Officer, GSK, commented, "We are grateful to the ACIP and CDC for recognizing the potential of Arexvy and look forward to partnering with public health officials, healthcare professionals, and payers to make it available for eligible older adults in the US before this year's RSV season begins."
The European Commission authorized Arexvy on June 7, 2023, as did the U.K.'s Medicines and Healthcare products Regulatory Agency on July 10, 2023, and Canada on August 4, 2023. GlobalData plc issued an AREXVY seven-year sales forecast on July 24, 2023, reaching $2.5 billion in 2029. On July 26, 2023, GSK estimated that nearly 80 million adults in the U.S. could receive an RSV shot for the first time. The RSV vaccine may launch in the U.S. and E.U. in the third quarter of 2023.
GlaxoSmithKline plc (LSE/NYSE: GSK) is located in Brentford, West London, England, and 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
On July 21, 2023, the U.S. CDC's Morbidity and Mortality Weekly Report confirmed the efficacy of 1 dose of the GSK vaccine in preventing symptomatic, laboratory-confirmed RSV-associated LRTD¶ was 82.6% (96.95% CI = 57.9%–94.1%) during the first RSV season and 56.1% (95% CI = 28.2%–74.4%) during the second season (Table 1).** Efficacy of 1 dose over two seasons was 74.5% (97.5% CI = 60.0%–84.5%) in preventing RSV-associated LRTD and 77.5% (95% CI = 57.9%–89.0%) in preventing medically attended RSV-associated LRTD.
The CDC Advisory Committee on Immunization Practices (ACIP) conducted an AREXVY review on June 21, 2023. Leonard Friedland, M.D. Vice President, Scientific Affairs and Public Health, GSK, resented updated data. The ACIP committee voted to recommend Arexvy for preventing RSV disease in adults aged 60 and older with shared clinical decision-making. The committee recommendations mean over 55 million older adults in the US could have access to RSV vaccination for the first time. 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. FDA conducted 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 FDA had accepted a Biologics License Application (BLA) (STN 125775/0) and granted a Priority Review for the RSVPreF3 OA vaccine candidate.
AREXVY Availability 2023
As of August 17, 2023, AREXVY was available in major retail pharmacies in the U.S. The U.S. FDA approved Arexvy on May 3, 2023. Europe approved Arexvy on June 7, 2023, followed by the U.K. and Canada. GSK plc stated announcements on regulatory progress in Australia and Japan are expected in 2023.
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.
Prescribing information was posted on May 3, 2023. 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 safety data following vaccination in multiple studies. The EMA confirmed on April 26, 2023, the most common side effects reported were headache, tiredness, muscle pain, joint pain, and injection site pain.
AREXVY Maternal Vaccine Candidate
AREXVY is not approved for use in persons <60 years of age. In a clinical study that enrolled pregnant individuals who received an investigational unadjuvanted RSV vaccine that contained the same RSVPreF3 antigen as AREXVY, an increase in preterm births was observed compared to pregnant individuals who received placebo (sucrose reconstituted with saline. In the vaccine and placebo groups, 6.81% and 4.95% of preterm births were reported, respectively. 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. As of May 27, 2023, this product was on hold.
GSK plc announced on August 17, 2023, AREXVY cost will be covered by most Medicare and commercial insurance plans in the U.S. under the Inflation Reduction Act, and patients with Medicare Part D will pay no out-of-pocket expenses. As part of the Affordable Care Act, AREXVY may be covered for commercially insured patients at no cost when administered in-network.
AREXVY News 2023
August 17, 2023 - Rob Truckenmiller, Senior Vice President, Head of US Vaccines, GSK, said: “We are excited to announce that AREXVY is now available to older adults in major retail pharmacies across the US ahead of this year’s RSV season."
August 4, 2023 - Henry Roberts, Executive Committee Member, COPD Canada, said: "Even if people with COPD or other chronic conditions have been taking sufficient steps to manage their illness.
June 22, 2023 - The U.S. CDC's ACIP voted 9 to 5 and recommended people 60 and older may receive an RSV vaccine dose using shared clinical decision-making.
June 7, 2023 - Dr. Alberto Papi, Full Professor of Respiratory Medicine and Head at the University of Ferrara said in a press release: "I am proud to have been part of the innovation that has resulted in a vaccine now being available to help protect eligible older adults across Europe from severe RSV disease for the first time."
May 3, 2023 - Peter Marks, M.D., Ph.D., director of the FDA's Center for Biologics Evaluation and Research, stated in a press release, "Today's 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 U.S."
April 26, 2023 - The EMA recommended a marketing authorization in the European Union for Arexvy.
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 positively impact public health with a unanimous vote on its 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 the 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 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 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.