ABRYSVO™ RSVpreF RSV Vaccine
Pfizer Inc.'s ABRYSVO™ RSVpreF (PF-06928316) bivalent prefusion F subunit vaccine is an approved older adult vaccine based on the crystal structure of prefusion F, a vital form of the viral fusion protein (F) that respiratory syncytial virus (RSV) uses to attack human cells. The vaccine candidate comprises two preF proteins selected to optimize protection against RSV A and B. ABRYSVO 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 critical viral protein that RSV uses to attack human cells.
On April 20, 2023, the NEJM published Original Articles: Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants, and Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. CONCLUSIONS: RSVpreF vaccine prevented RSV-associated LRTD and RSV-associated acute respiratory illness in older adults (≥60 years of age) without evident safety concerns. Pfizer announced in May 2023 it would be initiating multiple clinical trials evaluating RSVpreF in healthy children ages 2-5; children ages 5-18 with underlying medical conditions; adults ages 18-60 at high risk due to underlying medical conditions; and adults ages 18 and older who are immunocompromised and at high-risk for RSV.
ABRYSVO is indicated to prevent RSV infections and hospitalizations in older adults and infants. For infants, ABRYSVO is designed to stimulate the production of serum anti-F immunoglobulin G in the pregnant 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+), ABRYSVO vaccination prevents acute respiratory disease and lower respiratory tract disease (LRTD) caused by RSV. On August 21, 2023, the U.S. FDA approved Abrysvo for use in pregnant women to prevent LRTD and severe LRTD caused by RSV in infants from birth through six months. On September 22, 2023, Abrysvo was approved by the U.S. CDC's vaccine committee for use at 32 through 36 weeks gestational age of pregnancy during RSV season. On August 24, 2023, ABRYSVO became the first and only RSV vaccine approved in the European Union (EU) for older adults and pregnant women.
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. Pfizer's FDA application was granted Priority Review status and Fast Track and Breakthrough Therapy designations. According to GlobalData plc sales forecast published on July 24, 2023, Abrysvo could achieve sales of $1.7 billion in 2029.
ABRYSVO Vaccine U.S. CDC Review
The U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) conducted an ABRYSVO review on September 22, 2023, and February 23, 2023. The ACIP reviewed various presentations.
ABRYSVO Vaccine U.S. FDA Review
The U.S. Food and Drug Administration (FDA) Approved ABRYSVO™ for RSV prevention in Older Adults on May 31, 2023. On August 21, 2023, the FDA extended its approval for pregnant women for use at 32 through 36 weeks gestational age of pregnancy. The FDA conducted a Vaccines and Related Biological Products Advisory Committee (VRBPAC) ABRYSVO review on May 18, 2023. VRBPAC voted 14-0 regarding vaccine effectiveness in preventing severe disease in infants born to women vaccinated during pregnancy and voted 10-4 on immunization safety. In addition, the FDA's Briefing Document and Pfizer's EXECUTIVE SUMMARY were posted online. On February 28, 2023, the FDA conducted a VRBPAC meeting and published its Briefing Document, as did Pfizer. The VRBPAC voted that available data was 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 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. The FDA has accepted the BLA for priority review and has set a PDUFA action date of August 2023. In addition, 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. In November 2018, the FDA granted Fast Track status to RSVpreF.
ABRYSVO Availability 2023
ABRYSVO's U.S. FDA approval(s) suggests availability in late 2023. The European Medicines Agency (EMA) accepted Pfizer's ABRYSVO® marketing authorization application EMEA-002795-PIP01-20 under accelerated assessment for older adults and maternal immunization to help protect infants. On August 24, 2023, the EMA and European Commission issued approval. In February 2023, Pfizer Japan announced an application filed with the Ministry of Health, Labor, and Welfare for RSVPreF as a maternal immunization to help protect infants against RSV. In April 2023, Pfizer Canada announced that Health Canada accepted RSVpreF for review for individuals ages 60 and older and as a maternal immunization to help protect infants against RSV.
ABRYSVO Safety Information
Pfizer reported in August 2023 that ABRYSVO's potential risks include preterm birth. In clinical trials where ABRYSVO was compared to placebo, infants born to pregnant individuals experienced low birth weight (5.1% ABRYSVO versus 4.4% placebo) and jaundice (7.2% ABRYSVO versus 6.7% placebo. In addition, although not commonly reported, a dangerous hypertensive disorder known as pre-eclampsia occurred in 1.8% of pregnant individuals who received Abrysvo compared to 1.4% of pregnant individuals who received a placebo. To avoid the potential risk of preterm birth using ABRYSVO before 32 weeks of gestation, administer ABRYSVO as indicated in pregnant individuals at 32 through 36 weeks of gestational age.
ABRYSVO should not be given to anyone with a history of a severe allergic reaction (e.g., anaphylaxis) to any of its components. Fainting can happen after injectable vaccines, including ABRYSVO. Precautions should be taken to avoid falling and injury due to fainting. Adults with weakened immune systems, including those receiving medicines that suppress the immune system, may have a reduced immune response to ABRYSVO. In adults 60 years of age and older, the most common side effects (≥10%) were pain at the injection site, fatigue, headache, and muscle pain.
The FDA requires Pfizer to conduct postmarketing studies to assess the signal of serious risk of preterm birth and to assess hypertensive disorders of pregnancy, including pre-eclampsia.
For intramuscular use as a single approximately 0.5 mL dose.
ABRYSVO Coadministered With Vaccines
ABRYSVO is approved by the U.S. CDC for coadministration with Dtap, influenza, and COVID-19 vaccines, but not smallpox or yellow fever. Pfizer reported on May 2, 2023, positive top-line results from the Phase 3 study evaluating the safety and immunogenicity of its RSV bivalent vaccine candidate, PF-06928316 or RSVpreF, coadministered with seasonal inactivated influenza vaccine in adults 65 years and older. The study met its primary endpoint, demonstrating non-inferiority for all four flu strains and RSV groups. 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. ABRYSVO Pregnancy
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
September 22, 2023 - Members of the Advisory Committee on Immunization Practices voted 11-1 to recommend maternal RSV vaccine for pregnant people during 32 through 36 weeks gestation, using seasonal administration, to prevent RSV lower respiratory tract infection in infants.
August 21, 2023 - Eric A.F. Simões, M.D., Clinical Professor, Pediatrics-Infectious Diseases, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, said in a press release, "The approval of Pfizer's ABRYSVO is a major triumph as it helps ensure no delay in potential RSV protection during an infant's most vulnerable first six months of life and offers healthcare providers a new opportunity to help prevent severe RSV."
May 31, 2023 - Edward E. Walsh, MD, Professor of Medicine, University of Rochester Medical Center, and principal RENOIR investigator commented in a press release, "Today's FDA approval of ABRYSVO recognizes significant scientific progress, and importantly helps provide older adults potential protection against RSV and an opportunity to improve community health by helping prevent the disease."
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."
November 1, 2022 - Pfizer announced the RSVpreF investigational vaccine was well-tolerated with no safety concerns for vaccinated individuals and their newborns. The results met one of the study protocol's pre-specified regulatory success criteria.
March 24, 2022 - The U.S. FDA awarded the RSVpreF vaccine candidate Breakthrough Designation.
June 22, 2020 - Pfizer Announces the start of Phase 3 Clinical Trials. One study (NCT04424316) of the RSV vaccine candidate, RSVpreF, in pregnant women to evaluate the safety and efficacy of RSVpreF in infants born to immunized pregnant women 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.
RENOIR (NCT05035212) is a global, randomized, double-blind, placebo-controlled study designed to assess the efficacy, immunogenicity, and safety of a single dose of the vaccine in adults 60 years of age and older. The New England Journal of Medicine recently published the efficacy and safety results. RENOIR is ongoing, with efficacy data being collected in the second RSV season of the study.
MATISSE (NCT04424316) is a global, randomized, double-blinded, placebo-controlled Phase 3 study designed to evaluate the efficacy, safety, and immunogenicity of RSVpreF against medically attended lower respiratory tract illness (MA-LRT) and severe MA-LRTI due to RSV in infants born to healthy individuals vaccinated during pregnancy. The New England Journal of Medicine also recently published the efficacy and safety results.
On August 21, 2023, the FDA reported a clinical study that evaluated the effectiveness of Abrysvo in preventing LRTD and severe LRTD caused by RSV in infants born to individuals vaccinated during pregnancy. Among approximately 3,500 pregnant individuals who received Abrysvo, compared to about 3,500 pregnant individuals who received a placebo, Abrysvo reduced the risk of severe LRTD by 81.8% within 90 days after birth and 69.4% within 180 days after delivery. In a subgroup of pregnant individuals who were 32 through 36 weeks gestational age, of whom approximately 1,500 received Abrysvo and 1,500 received placebo, Abrysvo reduced the risk of LRTD by 34.7% and reduced the risk of severe LRTD by 91.1% within 90 days after birth when compared to placebo. Within 180 days after delivery, Abrysvo reduced the risk of LRTD by 57.3% and 76.5% for severe LRTD compared to placebo. The safety of Abrysvo was evaluated in two studies. In one study, approximately 3,600 pregnant individuals received a single dose of Abrysvo, and about 3,600 received a placebo. In the second study, about 100 pregnant individuals received Abrysvo, and approximately 100 received a placebo. The most commonly reported side effects by pregnant individuals who received Abrysvo were pain at the injection site, headache, muscle pain, and nausea.
In addition, although not commonly reported, a dangerous hypertensive disorder known as pre-eclampsia occurred in 1.8% of pregnant individuals who received Abrysvo compared to 1.4% of pregnant individuals who received a placebo. In the safety studies, infants' low birth weight and jaundice occurred more in the pregnant Abrysvo recipients than in pregnant placebo recipients.
The Phase 3 Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults. (RENOIR), at the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received the RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 points per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with the vaccine (12%) than with the placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date.
Pfizer has initiated two additional clinical trials evaluating ABRYSVO. One trial is conducted in children at higher risk for RSV disease, ages 2-<18.8. A second trial is evaluating adults ages 18-60 at higher risk for RSV due to underlying medical conditions, such as asthma, diabetes, and COPD, and adults ages 18 and older who are immunocompromised and at high risk for RSV.8 Pfizer also plans postmarketing studies and surveillance programs to describe the safety of the vaccine further.
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-reviewed 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.
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.