- Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced they have submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for approval of their Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine as a primary series and booster dose(s) for individuals 12 years of age and older.
On January 26, 2023, the U.S. FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted to harmonize the composition of COVID-19 vaccines across booster and primary series doses. If this sBLA is approved, people 12 years or older would be able to receive the companies' Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine for their primary series, rather than completing their primary series with the original vaccine (COMIRNATY® (COVID-19 Vaccine, mRNA)) before having access to the bivalent vaccine. Individuals in this age group who completed their primary series with the original vaccine or will complete it with the bivalent vaccine would still be eligible to receive a booster dose of the bivalent vaccine.
The original BLA for COMIRNATY as the primary series was approved in August 2021 for ages 16 years and older and later extended through an sBLA to include ages 12 through 15 years of age. Currently, the bivalent vaccine is available in the U.S. under Emergency Use Authorization (EUA) as a single booster dose for ages 5 years and older and as the third dose in the three-dose primary series for children 6 months through 4 years of age. As EUA is not meant to be a long-term status, this sBLA is the next step toward full regulatory approval of the bivalent vaccine.
This sBLA submission is supported by clinical, pre-clinical, and manufacturing data demonstrating the safety, tolerability, and immunogenicity of the bivalent vaccine. Among study participants over 55 years of age (n=~300 per group (individuals receiving the bivalent vaccine vs. comparator group receiving the original vaccine)), the bivalent vaccine met criteria for superiority over the original vaccine with respect to Omicron BA.4/BA.5-neutralizing antibodies elicited. Measured at one-month post-vaccination, the geometric mean ratio (GMR) of Omicron BA.4/BA.5-neutralizing antibodies was 2.91 (95% CI: 2.45, 3.44). For study participants aged 18 to 55 (n=~300) who received the bivalent vaccine, GMR was 0.98 (95% CI: 0.83, 1.16), which met criteria for non-inferiority compared to participants over 55 years of age who received the bivalent vaccine. For both age groups, the pattern of results was the same regardless of prior SARS-CoV-2 infection. The safety and tolerability profile of the bivalent vaccine remained similar to that of the original vaccine.1
The bivalent vaccine also induced a stronger neutralizing antibody response against newer Omicron sublineages in participants 55 years of age and older, including BA.4.6, BA.2.75.2, BQ.1.1 and XBB.1, compared to the original vaccine. For XBB.1, neutralizing antibody titers increased 4.8-fold (95% CI: 3.3,6.9) following a booster dose of the companies' bivalent vaccine and 1.5-fold (95% CI: 1.3,1.8) following a booster dose of the companies' original vaccine.1 This subset of individuals included those with and without evidence of prior infection. Similar results have been observe for XBB.1.5, which currently accounts for more than 80% of COVID-19 cases in the U.S.2,3
In the European Union (EU), the Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine was granted full marketing authorization (MA) for administration as a booster dose in individuals 5 years of age and older who have completed a primary vaccination course against COVID-19. The companies also plan to submit applications to the European Medicines Agency (EMA) for a variation of the MA to also include the bivalent vaccine as a primary course of vaccination in individuals 5 years of age and older and a line extension for the bivalent vaccine as a primary course of vaccination and booster for individuals 6 months of age through 4 years.
The Pfizer-BioNTech COVID-19 Vaccines (COMIRNATY) are based on BioNTech's proprietary mRNA technology and were developed by both BioNTech and Pfizer. BioNTech is the Marketing Authorization Holder for BNT162b2 (Original) and BNT162b2 Bivalent (Original/Omicron BA.4/BA.5) in the United States, the European Union, the United Kingdom, Canada and other countries, and the holder of emergency use authorizations or equivalents in the United States (jointly with Pfizer) and other countries.
U.S. INDICATION & AUTHORIZED USE
Pfizer-BioNTech COVID-19 Vaccine, Bivalent, (Original and Omicron BA.4/BA.5)
AUTHORIZED USE
Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5) is FDA authorized under Emergency Use Authorization (EUA) for use in individuals 5 years of age and older as a single booster dose administered at least 2 months after either:
- completion of primary vaccination with any authorized or approved COVID-19 vaccine; or
- receipt of the most recent booster dose with any authorized or approved monovalent* COVID-19 vaccine
*Monovalent refers to any authorized and approved COVID-19 vaccine that contains or encodes the spike protein of only the Original SARS-CoV-2 virus.
COMIRNATY® (COVID-19 Vaccine, mRNA)
INDICATION
COMIRNATY® (COVID-19 Vaccine, mRNA) is an FDA-approved COVID-19 vaccine for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.
AUTHORIZED USE
COMIRNATY® (COVID-19 Vaccine, mRNA) is authorized under Emergency Use Authorization (EUA) to provide:
Primary Series
- a third primary series dose to individuals 12 years of age and older who have certain kinds of immunocompromise
Pfizer-BioNTech COVID-19 Vaccine
AUTHORIZED USES
Pfizer-BioNTech COVID-19 Vaccine is FDA authorized under Emergency Use Authorization (EUA) for use in individuals 5 years of age and older to provide:
Primary Series
- a 2-dose primary series to individuals 5 years of age and older
- a third primary series dose to individuals 5 years of age and older with certain kinds of immunocompromise
Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent
AUTHORIZED USES
Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent are FDA authorized under Emergency Use Authorization (EUA) for use in individuals 6 months to 4 years of age to provide:
Primary Series
- a 3-dose primary series as follows:
- Dose 1: Pfizer-BioNTech COVID-19 Vaccine
- Dose 2: Pfizer-BioNTech COVID-19 Vaccine
- Dose 3: Pfizer-BioNTech COVID-19 Vaccine, Bivalent
EMERGENCY USE AUTHORIZATION
Emergency uses of the vaccines have not been approved or licensed by FDA but have been authorized by FDA under an Emergency Use Authorization (EUA) to prevent Coronavirus Disease 2019 (COVID-19) in individuals aged 6 months and older. The emergency uses are only authorized for the duration of the declaration that circumstances exist justifying the authorization of emergency use of the medical product under Section 564(b)(1) of the FD&C Act unless the declaration is terminated or authorization revoked sooner.
PFIZER-BIONTECH COVID-19 VACCINE, BIVALENT (ORIGINAL AND OMICRON BA.4/BA.5), COMIRNATY® (COVID-19 VACCINE, MRNA), AND PFIZER-BIONTECH COVID-19 VACCINE IMPORTANT SAFETY INFORMATION
Tell your vaccination provider about all of your medical conditions, including if you:
- have any allergies
- have had myocarditis (inflammation of the heart muscle) or pericarditis (inflammation of the lining outside the heart)
- have a fever
- have a bleeding disorder or are on a blood thinner
- are immunocompromised or are on a medicine that affects the immune system
- are pregnant, plan to become pregnant, or are breastfeeding
- have received another COVID-19 vaccine
- have ever fainted in association with an injection
• The vaccine may not protect everyone
• You should not get COMIRNATY (COVID-19 Vaccine, mRNA), the Pfizer-BioNTech COVID-19 Vaccine, or the Pfizer-BioNTech COVID-19 Vaccine, Bivalent if you have had a severe allergic reaction after a previous dose of COMIRNATY or the Pfizer-BioNTech COVID-19 Vaccine or any ingredient in these vaccines
• There is a remote chance that these vaccines could cause a severe allergic reaction. A severe allergic reaction would usually occur within a few minutes to 1 hour after getting a dose of the vaccine. For this reason, your vaccination provider may ask you to stay at the place where you received the vaccine for monitoring after vaccination. If you experience a severe allergic reaction, call 9-1-1 or go to the nearest hospital
Seek medical attention right away if you have any of the following symptoms:
• difficulty breathing, swelling of the face and throat, a fast heartbeat, a bad rash all over the body, dizziness, and weakness
• Myocarditis (inflammation of the heart muscle) and pericarditis (inflammation of the lining outside the heart) have occurred in some people who have received COMIRNATY® (COVID-19 Vaccine, mRNA) or Pfizer-BioNTech COVID-19 Vaccine or Pfizer-BioNTech COVID-19 Vaccine, Bivalent. The observed risk is higher among adolescent males and adult males under 40 years of age than among females and older males, and the observed risk is highest in males 12 through 17 years of age. In most of these people, symptoms began within a few days following receipt of the second dose of vaccine. The chance of having this occur is very low
Side effects that have been reported with these vaccines include:
- Severe allergic reactions
- Non-severe allergic reactions such as rash, itching, hives, or swelling of the face
- Myocarditis (inflammation of the heart muscle)
- Pericarditis (inflammation of the lining outside the heart)
- Injection site pain
- Tiredness
- Headache
- Muscle pain
- Chills
- Joint pain
- Fever
- Injection site swelling
- Injection site redness
- Nausea
- Feeling unwell
- Swollen lymph nodes (lymphadenopathy)
- Decreased appetite
- Diarrhea
- Vomiting
- Arm pain
- Fainting in association with injection of the vaccine
- Unusual and persistent irritability
- Unusual and persistent poor feeding
- Unusual and persistent fatigue or lack of energy
- Unusual and persistent cool, pale skin
- Dizziness
These may not be all the possible side effects of these vaccines. Call the vaccination provider or healthcare provider about bothersome side effects or side effects that do not go away.
- Individuals should always ask their healthcare providers for medical advice about adverse events. Report vaccine side effects to the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) Vaccine Adverse Event Reporting System (VAERS). The VAERS toll-free number is 1‐800‐822‐7967 or report online to www.vaers.hhs.gov/reportevent.html. In addition, individuals can report side effects to Pfizer Inc. at www.pfizersafetyreporting.com or by calling 1-800-438-1985
COMIRNATY® Full Prescribing Information and EUA Fact Sheets for Vaccination Providers and Recipients and Caregivers Fact Sheets:
COMIRNATY® Full Prescribing Information (12 years of age and older), DO NOT DILUTE, Gray Cap
EUA Fact Sheet for Vaccination Providers (12 years of age and older), DO NOT DILUTE, Gray Cap
EUA Fact Sheet for Vaccination Providers (5 through 11 years of age), DILUTE BEFORE USE, Orange Cap
EUA Fact Sheet for Recipients and Caregivers (12 years of age and older)
EUA Recipients and Caregivers Fact Sheet (5 through 11 years of age)
EUA Recipients and Caregivers Fact Sheet (6 months through 4 years of age)
