Extended findings from blinded mRNA-1273 vaccine pivotal trial include efficacy across subgroups, including elderly and with coexisting conditions.
A new report of the blinded, placebo-controlled trial of the mRNA-1273 SARS-CoV-2 vaccine (Moderna) that was pivotal to the US FDA granting Emergency Use Authorization (EUA) provides an additional 3 months of data, with new evidence of efficacy in preventing asymptomatic infection, and consistent efficacy across subgroups including elderly, the immunocompromised, and those with co-existing conditions.
The findings from a median follow-up of 2 months provided to the FDA are now complimented with additional data through term of the observer-blinded trial, which ended 5.3 months after the second dose.The study is continuing as open-label for up to 2 years, with participants in the placebo group given the option to receive the active vaccine.
"The data compiled through the completion of the blinded phase of the COVE trial provide further evidence of the safety and efficacy of mRNA-1273 in preventing symptomatic COVID-19 as well as preventing SARS-CoV-2 infection regardless of symptom and severity in adults, including those 65 years of age or older and those with coexisting conditions, and across various ethnic and racial groups," declared lead author Hana Mohammed El Sahly, MD, Departments of Molecular Virology and Microbiology and Medicine, Baylor College of Medicine, Houston, Texas, and colleagues of the COVE Study Group.
The investigators randomized a total of 30,415 participants between July 27 and October 23, 2020 to receive either active vaccine or placebo injection, and more than 96% received the second injection of the regimen.The final groups in the per-protocol analysis included 14,287 who received the vaccine and 14,164 the placebo.
El Sahly and colleagues report that vaccine efficacy in preventing COVID-19 illness was 93.2% (95% Confidence Interval [CI} 91.0-94.8), with 55 confirmed cases in the active vaccine group (9.6/1000 person-years; CI: 7.2-12.5) compared to 744 among those receiving placebo (136.6/1000 person-years; CI, 127-146.8).The efficacy in preventing severe disease was 98.2% (CI 92.8-99.6), with 2 cases in the vaccine group and 106 in the placebo group.
With the additional 3 months of follow-up, the investigators were able to report that the efficacy in preventing asymptomatic infection starting 14 days after the 2nd injection was 63% (CI, 56.6 to 68.5), with 214 cases in the vaccine group and 498 in the placebo group.
In addition to finding overall efficacy to be similar to that measure at 2 months,El Sahly and colleagues used data from a median follow-up of 148 days to determine that safety and efficacy were consistently high across subgroups, and that efficacy did not wane up to 4 months after the second injections.
"It is notable that the efficacies found in phase 3 trials of COVID-19 vaccines have thus far translated into high effectiveness in the general population, including effectiveness against variants of concern that are associated with reductions in neutralization, such as the B.1.351 (beta) and B.1.617.2 (delta) variants," the investigators observed."Additional data gathered from regions with current and potential surges in transmission of variants of concern are important toward informing strategies for administering additional doses of vaccine."
Although the investigators report that no safety concerns were identified in this phase 3 trial, they acknowledge that it was not sufficiently powered to detect rare events; which have subsequently surfaced during the global distribution of the vaccine.They further indicate that continued vigilance is warranted, including monitoring for anaphylactic reactions and for other potential unexpected reactions, such as myocarditis in adolescents and young adults.