Moderna FDA review
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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.
https://www.fda.gov/media/144434/download