ABRYSVO™ RSVpreF RSV Vaccine March 2023
Pfizer Inc.'s ABRYSVO™ RSVpreF (PF-06928316) bivalent vaccine candidate is based on the crystal structure of prefusion F, a vital form of the viral fusion protein (F) that RSV uses to attack human cells. The vaccine candidate comprises two preF proteins selected to optimize protection against respiratory syncytial virus (RSV) A and B. In addition, Pfizer engineered and tested numerous candidates and identified those that elicited a strong and stable immune response in pre-clinical evaluation, leading to the vaccine candidate Pfizer is evaluating in phase 3 clinical trials.
The ABRYSVO bivalent prefusion F subunit investigational vaccine candidate (RSVpreF) vaccine candidate builds on foundational basic science discoveries, including those made at the U.S. National Institutes of Health (NIH), which detailed the crystal structure of a key viral protein that RSV uses to attack human cells.
For infants, RSVpreF is designed to stimulate the production of serum anti-F immunoglobulin G in the mother, which can then be transferred to the fetus across the placenta and protected for the first six months of life when the risk of hospitalization is highest. For seniors (60 yr.+), RSVpreF vaccination prevents acute respiratory disease and lower respiratory tract disease caused by RSV.
On August 25, 2022, Pfizer announced a pre-planned, interim analysis of RSVpreF efficacy conducted by an independent, external Data Monitoring Committee (DMC) to assess protection against RSV-associated lower respiratory tract illness (LRTI-RSV) defined by two or more symptoms demonstrated vaccine efficacy: 66.7% (96.66% CI: 28.8%, 85.8%). In addition, the phase 3 study found vaccine efficacy of 81.8% was observed against severe medically attended lower respiratory tract illness due to RSV in infants from birth through the first 90 days of life, with high efficacy of 69.4% demonstrated through the first six months of life.
A $27.5 million grant from Bill & Melinda Gates Foundation to Pfizer on September 28, 2022, will support the development of an affordable multidose to deliver the RSV vaccine candidate in lower-income countries via public sector purchasers, including Gavi.
New York-based Pfizer Inc.'s (NYSE: PFE) portfolio includes medicines, vaccines, and many of the world's best-known consumer healthcare products. ABRYSVO™ trademark Application Filed: 2021-09-09.
ABRYSVO Vaccine U.S. CDC Review
The U.S. CDC Advisory Committee on Immunization Practices (ACIP) conducted an ABRYSVO review on February 23, 2023. Pfizer presented to the vaccine advisory committee, including but not limited to an Economic Analysis of RSV Vaccination in Older Adults and Evidence to Recommendations Framework.
ABRYSVO Vaccine U.S. FDA Review 2023
The U.S. FDA scheduled a Vaccines and Related Biological Products Advisory Committee (VRBPAC) ABRYSVO review meeting for (STN 125769/0) on February 28, 2023. The FDA published its Briefing Document, as did Pfizer. The VRBPAC voted that available data is adequate to support the safety and effectiveness of RSVpreF. The Committee voted 7 to 4 on safety and 7 to 4 on effectiveness.
On February 21, 2023, the company announced the FDA had accepted for review a BLA (STN 125769) for RSVpreF for the prevention of medically attended lower respiratory tract illness (MA-LRTI) and severe MA-LRTI caused by RSV in infants from birth up to six months of age by active immunization of pregnant individuals. And the FDA has accepted the BLA for priority review and has set a PDUFA action date of August 2023.
Pfizer confirmed on December 7, 2022, that the U.S. FDA accepted for priority review a Biologics License Application (STN 125769/0) for RSVpreF in individuals 60 years of age and older. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA on the RSVpreF application is in May 2023. RSVpreF previously received Breakthrough Therapy Designation from the FDA for infants from birth up to six months of age by active immunization of pregnant women and for seniors on March 24, 2022.
In November 2018, the U.S. Food and Drug Administration (FDA) granted Fast Track status to RSVpreF. In a Phase 2 Efficacy study, Pfizer reported that the RSV vaccine showed 100% efficacy against mild to moderate RSV illness in adults (N=62). On June 24, 2022, the peer-review journal NEJM published an Original Article based on a phase 2 study findings that concluded: that the RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. In addition, no evident safety concerns were identified.
ABRYSVO Vaccine Europe
The European Medicines Agency (EMA) accepted Pfizer's marketing authorization application EMEA-002795-PIP01-20 under accelerated assessment for its RSV vaccine candidate for both older adults and maternal immunization to help protect infants, with a decision expected in the second half of 2023.
The RSVpreF vaccine is indicated to prevent RSV infections and hospitalizations in infants and older adults, says Pfizer. Globally, there are an estimated 33 million cases of RSV annually in children under five years of age, with about 3 million hospitalized and up to approximately 120,000 dying each year from complications associated with the infection. Nearly half of pediatric hospitalizations and deaths occur in infants less than six months of age. In addition, it is estimated that in the United States, approximately 177,000 older adults are hospitalized annually because of RSV, says the U.S. CDC.
ABRYSVO Coadministered With Influenza Vaccines
Pfizer's Briefing Document, presented on February 28, 2023, offered limited insights into the side effects or effectiveness of ABRYSVO when coadministered with influenza vaccines in Older Adults. The U.S. FDA staff concurred that VE for the 2022-2023 flu season could not be ascertained.
In a phase 2b clinical trial, we randomly assigned pregnant women at 24 through 36 weeks' gestation to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or a placebo. Across the range of assessed gestational ages, infants of immunized women had similar titers in umbilical-cord blood and similar transplacental transfer ratios. STUDY CONCLUSIONS: RSVpreF vaccine-elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns.
A post-hoc efficacy analysis estimated a VE of 84.7% (95% CI 21.6-97.6) against medically attended RSV-associated lower respiratory tract illness and 91.5% (95% CI -5.6 to 99.8) against severe RSV-associated lower respiratory tract illness.
A phase III trial of a single 120 μg dose of RSVpreF without aluminum hydroxide is ongoing. The phase 2b study evaluated one of 2 dose levels of the vaccine, 120 or 240 μg, formulated with or without aluminum hydroxide.
ABRYSVO News 2023
February 28, 2023 - The U.S. FDA VRBPAC committee voted (in favor of proceeding with ABRYSVO's BLA for older adults. Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Vaccine Research and Development, Pfizer, stated in a press release, "We are encouraged by the outcome of today's VRBPAC meeting as it is a testament to the strength of our science and dedication to bringing this important vaccine candidate to the market. We look forward to working with the FDA as it completes the review of our application."
February 21, 2023 - "If approved, RSVpreF would help protect infants at their first breath from the devastating effects of this infectious disease, which though well-known, has been particularly evident throughout this RSV season," said Annaliesa Anderson, Ph.D., Senior Vice President and Chief Scientific Officer, Vaccine Research & Development, Pfizer, in a press release.
December 7, 2022 - Annaliesa Anderson, Ph.D., SVP and Chief Scientific Officer, Vaccine Research & Development, Pfizer, commented in a press release, "The FDA's acceptance of the BLA for our RSV vaccine candidate is an important regulatory milestone in Pfizer's efforts to help protect older adults against RSV and demonstrates additional progress toward what has been an elusive public health goal – reducing the overall burden associated with this infectious disease."
November 1, 2022 - Pfizer announced the RSVpreF investigational vaccine was well-tolerated with no safety concerns for both vaccinated individuals and their newbornsAndnd the results met one of the study protocol's pre-specified regulatory success criteria.
June 23, 2022 - An Editorial by Marie R. Griffin, M.D., M.P.H., Vanderbilt University School of Medicine, was published by the NEJM - A Challenge to Respiratory Syncytial Virus Illness in Adults. This editorial was related to the phase 2 study results presented in an Original Article.
April 28, 2022 - Pfizer's RSV vaccine candidate RSVpreF vaccine-elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns in a phase 2b study.
March 24, 2022 - The U.S. FDA awarded the RSVpreF vaccine candidate its second Breakthrough Designation.
July 30, 2021 - Pfizer announced a challenge study, giving vaccines to 62 adults under 50, who were then intentionally infected with RSV to see if the shot worked, showed "100% observed efficacy against mild to moderate symptomatic infection resulting from RSV."
June 22, 2020 - Pfizer Announces the start of (4) Phase 3 Clinical Trials. One study (NCT04424316) of the respiratory syncytial virus (RSV) vaccine candidate, RSVpreF, in pregnant women to evaluate the safety and efficacy of RSVpreF in infants born to immunized pregnant women as compared to placebo.
May 22, 2018 - Pfizer Inc. announced that it had started a Phase 1/2 trial of its respiratory syncytial virus vaccine candidate in healthy adult volunteers. The highest risk of severe outcomes from RSV occurs in the first months of life.
RSVpreF RSV Clinical Trials
RSV preF is currently being tested in several clinical trials.
In August 2022, Pfizer announced positive top-line results of an interim efficacy analysis for RENOIR. The Phase 3 RENOIR trial of RSVpreF is a global, randomized, double-blind, placebo-controlled study that expects to enroll approximately 30,000 participants 60 years and older. Vaccine efficacy of 85.7% was observed in participants with more severe disease primary endpoint of LRTI-RSV defined by analysis of three or more RSV-associated symptoIn addition, the investigational vaccine was well-tolerated with no safety concerns.
In April 2020, positive top-line results were achieved for a Phase 2b proof-of-concept study of RSVpreF, which evaluated the safety, tolerability, and immunogenicity of RSVpreF in vaccinated pregnant women ages 18 through 49 and their infants. Pfizer will publish outcomes from this clinical trial at a future date.