“1. Executive Summary: … ). ). 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 …
2. Background
2.3. U.S. Requirements to Support Issuance of an EUA for a Biological Product: … In the event an EUA is issued for this product, it would still be considered unapproved and it would be under further investigation…
2.6 Safety and Effectiveness Information Needed to Support an EUA
Effectiveness data: Issuance of an EUA requires a determination that the known and potential benefits of the vaccine outweigh the known and potential risks. For a preventive COVID-19 vaccine to be potentially administered to millions of individuals, including healthy individuals, data adequate to inform an assessment of the vaccine’s benefits and risks and support issuance of an EUA would include meeting the prespecified success criteria for the study’s primary efficacy endpoint.
5. FDA Review of Clinical Safety and Effectiveness Data ...
5.2 Study mRNA-1273-P301
5.2.1 Design …
Primary Efficacy Endpoint: The primary efficacy endpoint was efficacy of the vaccine to prevent protocol-defined COVID-19 occurring at least 14 days after the second dose in participants with negative SARS-CoV-2 status at baseline…
5.2.6 Safety: … The safety analyses presented in this review are largely derived from the November 11, 2020 dataset that was the basis for the November 30, 2020 EUA request. FDA has not independently verified the complete safety dataset and analyses from the cutoff date of November 25, 2020.
Pregnancies: Study participants of childbearing potential were screened for pregnancy prior to each vaccination, with a positive test resulting in exclusion or discontinuation from study vaccination… Pregnancy outcomes are otherwise unknown at this time.
6. Sponsor’s Plans for Continuing Blinded, Placebo-Controlled Follow-Up: …
ModernaTX is evaluating the opportunity to amend the protocol to proactively reconsent participants who received placebo to be offered mRNA-1273 vaccination and to remain in the trial, enabling ModernaTX to continue to collect the relevant safety and effectiveness data over the entire two years of follow-up while increasing the likelihood of retaining participants on trial.
8. Benefit/Risk Assessment in the Context of Proposed Indication and Use Under EUA
8.2 Unknown Benefits/Data Gaps
Duration of Protection: As the interim and final analyses have a limited length of follow-up, it is not possible to assess sustained efficacy over a period longer than 2 months…
Effectiveness in certain populations at high-risk of severe COVID-19: Although the proportion of participants at high risk of severe COVID-19 is adequate for the overall evaluation of safety in the available follow-up period, the subsets of certain groups such as immunocompromised individuals (e.g., those with HIV/AIDS) are too small to evaluate efficacy outcomes.
Effectiveness in individuals previously infected with SARS-CoV-2: … [T]he study was not designed to assess the benefit in individuals with prior SARS-CoV-2 infection.
Vaccine effectiveness against mortality: A larger number of individuals at high risk of COVID-19 and higher attack rates would be needed to confirm efficacy of the vaccine against mortality.
Vaccine effectiveness against transmission of SARS-CoV-2: Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination… Additional evaluations including data from clinical trials and from vaccine use post-authorization will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.
8.4 Unknown Risks/Data Gaps
Safety in certain subpopulations: There are currently insufficient data to make conclusions about the safety of the vaccine in subpopulations such as children less than 16 years of age, pregnant and lactating individuals, and immunocompromised individuals.
10. Appendix A. Phase 1 and 2 Studies
Study Design: Study mRNA-1273-P201 is an ongoing phase 2a, randomized, observer-blind, placebo-controlled, dose-confirmation study to evaluate the safety, reactogenicity, and immunogenicity of mRNA-1273 in healthy adults 18 years and older.”
"“Vaccine-enhanced disease. Available data do not indicate a risk of vaccine-enhanced disease, and conversely suggest effectiveness against severe disease within the available follow-up period. However, risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure.”"