The FDA shared the briefing document application for licensure of a booster dose for COMIRNATY (COVID-19 Vaccine, mRNA), available here. As of today, only 17% of Americans have raised their sleeve for a booster. COMIRNATY is the only FDA approved COVID-19 Vaccine. It has been widely studied and the safety profile proves it to be the most researched and safest of all COVID-19 vaccines used in the world and more studied and scrutinized than the EUA monoclonal antibody treatment, Regeneron. COMIRNATY is the booster my parents received and the booster Brad and I received. Speak with your doctor about your safety concerns. Here is some more to read to make the most informed choice.
As of today the FDA now recommends COVID-19 booster shots to ALL adults to mitigate the waning of antibody titers against the spike protein in some twice- mRNA vaccinated individuals and the sad reality of rising coronavirus cases in many parts of the world.
The 23-page document includes Section 6.3. for the proposed use of a COMIRNATY booster dose with Section 6.4 sharing the FDA review of clinical data from Study C4591001.
Study C4591001 is described below:
“Design Study C4591001 is ongoing. The study was initially designed to evaluate two vaccine candidates and several dosages in healthy adults in the United States (Phase 1), of which 24 participants (n=12 per age group: 18-55 years and 65-85 years) received a 2-dose primary series of BNT162b2 (30 µg); the study population included healthy men and women and excluded participants at high risk of SARS-CoV-2 infection or with serological evidence of prior or current SARS-CoV-2 infection.
The Phase 2/3 portion of the study is being conducted in the United States, Argentina, Brazil, Germany, South Africa and Turkey. Please see the Summary Basis for Regulatory Action for the approval of a 2-dose primary series of COMIRNATY for study design details. 1 Enrolled Phase 2/3 participants were initially stratified by age (18-55 years and >55 years), with the goal of older adults (>55 years of age) comprising 40% of the total study population. The protocol was later amended to include adolescents 16 and 17 years of age. The study population included participants at higher risk for acquiring COVID-19 and at higher risk of severe COVID19, such as health care workers, participants with autoimmune disease, and participants with chronic but stable medical conditions such as hypertension, asthma, diabetes, and infection with HIV, hepatitis B or hepatitis C. Participants were randomized 1:1 to receive two doses of either BNT162b2 or saline placebo 3 weeks apart. Per protocol, since December 14, 2020, following issuance of the Emergency Use Authorization for the Pfizer-BioNTech COVID-19 Vaccine, Phase 2/3 participants ≥16 years of age in the vaccine and placebo groups were progressively unblinded to their treatment assignment (when eligible for vaccination per local recommendations), and participants originally randomized to placebo were offered vaccination with BNT162b2 under the study protocol with continuing follow-up for safety and COVID-19- related outcomes. In February and March 2021, the protocol was amended to evaluate the safety and immunogenicity of booster dose of BNT162b2 in Phase 1 participants (N=12 per age cohort: 18- 55 years and 65-85 years) and a subset of Phase 2/3 adults (N=300, ages 18-55 years), who completed the 2-dose primary vaccination series with 30 µg BNT162b2. A booster dose of 30 µg BNT162b2 was administered approximately 7 to 9 months after a primary series for Phase 1 participants and approximately 6 months after a primary series for Phase 2/3 participants.
Immunogenicity evaluation
The effectiveness of the booster dose is based on an immunobridging analysis from the Phase 2/3 booster participants comparing 50% neutralizing antibody titers against the reference strain (recombinant USA-WA1/2020) at 1 month after the booster dose to those observed at 1 month post-primary series among subjects without evidence of prior SARS-CoV-2 infection. Immunobridging analyses included hypothesis testing for:
GMTs of SARS-CoV-2 neutralizing antibodies at 1 month after the booster dose vs. those values 1 month after a primary series, using a 1.5-fold non-inferiority margin as the success criterion for the lower bound of the confidence interval around the geometric mean ratio (GMR), and percentage of participants with seroresponse (≥4-fold rise from baseline) at 1 month after the booster dose vs. 1 month after a primary series, using a -10% non-inferiority margin as the success criterion for the lower bound of the confidence interval around the difference between seroresponse rates. In the protocol-specified analysis of seroresponse, the baseline neutralizing antibody titer for determining seroresponse to the booster dose was the pre-Dose 1 titer (same baseline titer as used for determining seroresponse to the primary series). However, FDA also asked Pfizer to conduct a post hoc seroresponse analysis using the pre-booster dose titer as the baseline for determining the booster dose seroresponse (defined as ≥4-fold increase from the pre-booster dose baseline titer). Exploratory analyses of neutralizing antibody titers elicited by the BNT162b2 primary series and a 30 µg BNT162b2 booster dose against the reference strain (Wuhan) of SARS-CoV-2 and the
Beta and Delta variants were performed using samples from the Phase 1 study population. Discussion of these exploratory analyses in this briefing document is focused on the Delta variant, since it is currently the predominant circulating variant in the US. Safety evaluation Phase 1 participants and Phase 2/3 participants recorded reactogenicity assessments and antipyretic/pain medication use from Day 1 through Day 7 after booster in an e-diary. Reactogenicity assessments included solicited injection site reactions (pain, redness, swelling) and systemic AEs (fever, fatigue, headache, chills, vomiting, diarrhea, new or worsened muscle pain, and new or worsened joint pain). Other safety assessments included: AEs occurring within 30 minutes after each dose, non-serious unsolicited AEs from Dose 1 through 1 month after the booster dose, and serious AEs (SAEs) from the booster dose to the data cut-off date of June 17, 2021 (Phase 2/3) or May 13, 2021 (Phase 1). Analysis populations pertaining to the 30 µg BNT162b2 booster dose
Safety: All randomized participants who received a booster dose of 30 µg BNT162b2. Analyses of reactogenicity endpoints were based on a subset of the safety population that included participants with any e-diary data reported after vaccination.
All-available immunogenicity: All participants who received a primary series of 30 µg BNT162b2 at initial randomization, received a booster dose of 30 µg BNT162b2, and had at least 1 valid and determinate immunogenicity result after the booster dose.
Evaluable immunogenicity: All eligible participants who received a primary series of 30 µg BNT162b2 as initially randomized, with Dose 2 received within 19-42 days after Dose 1, received a booster dose of 30 µg BNT162b2, had at least 1 valid and determinate immunogenicity result after the booster dose from a blood collection within 28-42 days after the booster dose, and had no other important protocol deviations as determined by the clinician.
6.4.2. Demographics and disposition
Demographic characteristics of the Phase 1 and Phase 2/3 study participants who received a BNT162b2 (30 µg) booster dose are summarized in Table 2 below. Booster recipients were predominantly White. Phase 1 excluded individuals with comorbidities that confer risk for severe COVID-19 (i.e., obesity, diabetes with or without complications, chronic pulmonary disease, cardiovascular conditions such as hypertension, congestive heart failure, ischemic heart disease, HIV). Approximately 20% of booster recipients in Phase 2/3 had such comorbidities.
Among the 24 Phase 1 study participants randomized to the BNT162b2 primary series, 23 participants received a BNT162b2 (30 µg) booster dose (11 adults ages 18-55 years and 12 adults ages 65-85 years). One participant in the 18-55 year-old cohort declined to receive a BNT162b2 booster dose. All 23 Phase 1 participants who received the booster dose were included in the safety analyses, and the booster dose evaluable immunogenicity population. The disposition of Phase 2/3 study participants who received a BNT162b2 (30 µg) booster dose is summarized in Table 3 below.
