- Jennifer Middleton, MD, MPH
In the last week, two pharmaceutical companies have released preliminary data indicating that their mRNA vaccines against the SARS-CoV-2 virus are efficacious and safe. Critics are arguing that these preliminary data releases only serve to drive up manufacturers' stock prices, but others are gladly grasping at their potential to help end the COVID-19 pandemic. Before these vaccines will be released to the United States (US) public, though, they must be evaluated by the Food and Drug Administration (FDA).
To be approved by the FDA, vaccine manufacturers must prove their product's efficacy and safety through a rigorous, methodological process. First, manufacturers must submit an Investigational New Drug application, detailing the vaccine's proposed mechanism of action and previous animal model study results. Then,
Pre-marketing (pre-licensure) vaccine clinical trials are typically done in three phases, as is the case for any drug or biologic. Initial human studies, referred to as Phase 1, are safety and immunogenicity studies performed in a small number of closely monitored subjects. Phase 2 studies are dose-ranging studies and may enroll hundreds of subjects. Finally, Phase 3 trials typically enroll thousands of individuals and provide the critical documentation of effectiveness and important additional safety data required for licensing.
As of November 12, 2020, the World Health Organization (WHO) was tracking 48 candidate vaccines. Nine of those candidate vaccines are in phase 3 trials, and two of them recently released interim data analyses. The Pfizer/BioNTech vaccine, BNT162b2, is currently in a phase 3 trial with over 43,000 participants; interim analysis suggests it is at least 90% effective. The National Institutes of Health (NIH)/Moderna vaccine, mRNA-1273, also in a phase 3 trial (the "COVE" trial) with over 30,000 participants, announced similar findings in their interim analysis with 94.5% effectiveness.
Vaccine manufacturers can apply for an Emergency Use Authorization (EUA) to bypass the full approval process; the FDA has already issued EUAs during the pandemic for several SARS-CoV-2 diagnostic tests as well as for therapeutics such as baricitinib, remdesivir (in pediatric patients; already FDA-approved in adults), and convalescent plasma. (The FDA revoked the EUAs for hydroxychloroquine and chloroquine in June 2020.) The FDA has posted guidance for vaccine EUA applications and has pledged to make all submitted data for EUAs transparently available to the public.
As Dr. Kenny Lin has previously pointed out on the blog, it's unlikely that a vaccine alone will stem the pandemic's tide; handwashing, social distancing, and face coverings remain essential. You can estimate the risk of an unknowingly COVID-19 infected person at your gathering using this online tool; you'll likely see why the Centers for Disease Control and Prevention (CDC) is recommending we only gather with immediate family for the upcoming Thanksgiving holiday.
We'll continue to regularly update the AFP By Topic on Coronavirus Disease 2019 (COVID-19), and, as 2020 comes to a close, don't forget that the AAFP has a robust offering of CME learning activities about COVID-19.