Moderna COVID-19 Vaccine
VRBPAC Briefing Document
1. Executive Summary
On November 30, 2020, ModernaTX (the Sponsor) submitted an Emergency Use Authorization
(EUA) request to FDA for an investigational COVID-19 vaccine (mRNA-1273) intended to
prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The vaccine is based on the SARS-CoV-2 spike glycoprotein (S) antigen encoded by RNA and
formulated in lipid nanoparticles (LNPs). The proposed use under an EUA is for active
immunization for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of
age and older. The proposed dosing regimen is 2 doses, 100 μg each, administered 1 month
apart.
The EUA request includes safety and efficacy data from an ongoing Phase 3 randomized,
double-blinded and placebo-controlled trial of mRNA-1273 in approximately 30,400 participants.
The primary efficacy endpoint is the reduction of incidence of COVID-19 among participants
without evidence of SARS-CoV-2 infection before the first dose of vaccine in the period after 14
days post-dose 2. In an interim analysis conducted using a data cutoff of November 7, 2020, a
total of 27,817 participants randomized 1:1 to vaccine or placebo with a median 7 weeks of
follow-up post-dose 2 were included in the per-protocol efficacy analysis population of
participants without evidence of SARS-CoV-2 infection prior to vaccination. Efficacy in
preventing confirmed COVID-19 occurring at least 14 days after the second dose of vaccine
was 94.5.0% (95% CI 86.5%, 97.8%) with 5 COVID-19 cases in the vaccine group and 90
COVID-19 cases in the placebo group. Subgroup analyses of the primary efficacy endpoint
showed similar efficacy point estimates across age groups, genders, racial and ethnic groups,
and participants with medical comorbidities associated with high risk of severe COVID-19.
Secondary efficacy analyses suggested benefit of the vaccine in preventing severe COVID-19
(11 protocol-defined severe COVID-19 cases in the placebo group vs. 0 cases in the vaccine
group), in preventing COVID-19 following the first dose, and in preventing COVID-19 in
individuals with prior SARS-CoV-2 infection, although available data for some of these
outcomes did not allow for firm conclusions. Efficacy data from the final scheduled analysis of
the primary efficacy endpoint (data cutoff of November 21, 2020, with a median follow-up of >2
months post-dose 2) demonstrated a VE of 94.1% (95% CI 89.3%, 96.8%), with 11 COVID-19
cases in the vaccine group and 185 COVID-19 cases in the placebo group and was consistent
with results obtained from the interim analysis. The VE in this analysis when stratified by age
group was 95.6% (95% CI: 90.6%, 97.9%) for participants 18 to <65 years of age and 86.4%
(95% CI: 61.4%, 95.5%) for participants ≥65 years of age. A final secondary efficacy analysis
also supported efficacy against protocol-defined severe COVID-19, with 30 cases in the placebo
group vs. 0 cases in the vaccine group.
Safety data from a November 11, 2020 interim analysis of approximately 30,350 participants
≥18 years of age randomized 1:1 to vaccine or placebo with a median of 7 weeks of follow-up
after the second dose supported a favorable safety profile, with no specific safety concerns
identified that would preclude issuance of an EUA. These safety data are the primary basis of
FDA’s safety review. On December 7, 2020, the Sponsor submitted additional follow-up data
from these participants with a cutoff of November 25, 2020, which represents a median of 9
weeks (>2 months) of follow-up post-dose 2. Key safety data from this later submission,
including death, other serious adverse events, and unsolicited adverse events of interest were
independently verified and confirmed not to change the safety conclusions from the interim
safety analysis.
The most common solicited adverse reactions associated with mRNA-1273 were injection site
pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and