By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The FDA has granted full approval for the Pfizer-BioNTech COVID-19 vaccine, a messenger RNA (mRNA) platform, for use in individuals ≥ age 16 years. It has been available under an emergency use authorization (EUA) since Dec. 11, 2020. The EUA will remain for individuals ages 12 to 15 years and as a third dose in certain immunocompromised patients.1 The agency granted a priority review and fast-track breakthrough designation. The vaccine will be marketed as Comirnaty.
Comirnaty can be administered to individuals ≥ age 16 years to prevent COVID-19.2
The recommended dose is two intramuscular doses (0.3 mL each) administered three weeks apart.2 This solution is available as 0.3 mL single-dose vials.
Comirnaty is the first COVID-19 vaccine to receive full FDA approval.
The commonly reported adverse reactions (reactogenicity) were pain at injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), and fever (17.8%).2 Systemic adverse events (e.g., fever, fatigue, muscle/joint pain) appeared more common with the second dose.2 There is a higher rate of myocarditis and pericarditis, particularly in men younger than age 40 years, with the highest risk in men age 12-17 years (estimated 65-200 cases/million doses administered).3 Most recover without sequelae. The vaccine requires specific storage conditions, preferably in an ultra-low temperature freezer between -90°C to -60°C, although limited excursion outside this range may be permitted.2 The vaccine may be less effective against the B.1.617.2 (delta) variant.
Comirnaty elicits an immune response to the spike glycoprotein of SARS-CoV-2. Efficacy data were based mainly on participants age 16 years and older who were enrolled from July 27, 2020, follow-up through March 13, 2021, representing up to six months of follow-up after dose 2. Viral variants during the study were mainly B.1.1.7 (alpha) and B1.351 (beta). There were approximately 20,000 subjects in each of the vaccine and placebo groups. Vaccine efficacy (VE) was based on first laboratory-confirmed COVID-19 occurrence from seven days after dose 2 in participants without evidence of prior infection. VE rate (%) was 91.1 (95% CI, 88.8-93.1). This was consistent for ages 16 through 64 years and age ≥ 65 years. VE (%) against first severe disease was 95.3 (95% CI, 70.9-99.9).
The delta variant has become the prevalent strain worldwide, and the effectiveness of the current vaccines against this more transmissible variant is unclear, since VE was established during alpha variant dominance. Several observational studies have been conducted. The authors of a U.K. case-controlled study estimated the effectiveness of Comirnaty against the delta and alpha variants.4 A two-dose regimen of Comirnaty showed an adjusted vaccine effectiveness of 88% (95% CI, 85-90.1).
The CDC conducted an analysis of a cohort study of healthcare personnel, first responders, and other essential and frontline workers in eight U.S. locations to assess vaccine effectiveness during the alpha predominate vs. delta predominate periods.5 Among 4,217 participants, 65% received Comirnaty and 33% received the Moderna vaccine (mztns-1273). The CDC estimated the adjusted VE to be 66% during the delta predominate period vs. 91% in the alpha predominate period.
The authors of a preprint Mayo Clinic observational study reported the effectiveness of Comirnaty dropped to 42% while mRNA-1273 dropped to 76% during the month where the delta variant became dominant in Minnesota.6 However, both effectively prevented hospitalization, ICU admission, and death. The most recently reported data to the Advisory Committee on Immunization Practices (ACIP) indicate vaccine effectiveness against hospitalization ranging from 75% to 95%.7 Effectiveness in those ages > 75 years has dropped slightly, but remains > 80%.
Comirnaty is the first COVID-19 vaccine to be approved by the FDA. This step is important because many vaccine-hesitant individuals cited the lack of approval as a reason they were delaying vaccination. Moderna also has applied for full FDA approval for their mRNA vaccine, with approval anticipated before the end of the year. ACIP has issued interim recommendation for use of Comirnaty in individuals age 12-15 years and age > 16 years.8 ACIP also has issued an interim recommendation for a third dose for moderately to severely immunocompromised patients. The recommendation for a booster shot for all vaccinated individuals is pending ACIP review.9 As of Sept. 10, 2021, more than 96 million people in the United States have been fully vaccinated with Comirnaty.10
- U.S. Food & Drug Administration. FDA approves first COVID-19 vaccine. Aug. 23, 2021.
- Pfizer-BioNTech. Comirnaty prescribing information. August 2021.
- U.S. Food & Drug Administration. Summary basis for regulatory action. Aug. 23, 2021.
- Lopez Bernal J, Andrews N, Gower C, et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 (delta) variant. N Engl J Med 2021;385:585-594.
- Fowlkes A, Gaglani M, Groover K, et al. Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection among frontline workers before and during B.1.617.2 (delta) variant predominance — Eight U.S. locations, December 2020-August 2021. MMWR Morb Mortal Wkly Rep 2021;70:1167-1169.
- Puranik A, Lenehan PJ, Silvert E, et al. Comparison of two highly-effective mRNA vaccines for COVID-19 during periods of alpha and delta variant prevalence. medRxiv 2021;2021.08.06.21261707. doi: 10.1101/2021.08.06.21261707. [Preprint].
- Centers for Disease Control and Prevention. Framework for booster doses of COVID-19 vaccines. Aug. 30, 2021.
- Centers for Disease Control and Prevention. Interim clinical considerations for use of COVID-19 vaccines currently approved or authorized in the United States. Page last reviewed Aug. 31, 2021.
- Centers for Disease Control and Prevention. COVID-19 vaccine booster shot. Updated Sept. 1, 2021.
- Centers for Disease Control and Prevention. COVID-19 vaccinations in the United States. Data as of Sept. 10, 2021.