December 17, 2020 - The FDA’s Vaccines and Related Biological Products Advisory Committee has voted 20-0 with 1 abstention to support the benefit-risk profile associated with the coronavirus disease 2019 vaccine mRNA-1273.
The FDA’s Vaccines and Related Biological Products Advisory Committee has voted 20-0 with 1 abstention to support the benefit-risk profile associated with the coronavirus disease 2019 vaccine mRNA-1273.
The proposed use under the Emergency Use Authorization (EUA) request to the regulatory agency for the vaccine developed by the American biotechnology company, Moderna, is for active immunization for the prevention of the virus caused by SARS-CoV-2 in individuals who are aged 18 years and older. The proposed dosage for the vaccine is 2 doses of 100 μg, to be delivered 1 month apart.
"Both the Pfizer and Moderna vaccines are exciting developments in our global battle against the COVID-19 pandemic. Given how these vaccines were developed (without the presence of the full virus) we strongly feel they should likely be safe for almost all individuals, especially cancer patients," Ruben A. Mesa, MD, FACP, executive director of Mays Cancer Center at UT Health San Antonio MD Anderson, told OncLive. "Although the Mays Cancer Center at UT Health San Antonio MD Anderson is advising all patients to check with their doctors and healthcare teams, we envision the vast majority should and will receive [a vaccine] as crucial protection against the virus. It is possible that patients on the most aggressive chemotherapies or very immunocompromised may develop less protection from the virus, it still is worthwhile likely for them to receive."
The EUA was based on safety and efficacy findings from a randomized, double-blinded, placebo-controlled, phase 3 trial that examined mRNA-1273 in about 30,400 individuals. The primary efficacy end point of the trial was reduction in the incidence of COVID-19 in patients without any evidence of SARS-CoV-2 infection prior to the administration of the first vaccine dose in the 2-week period following the second dose.
At a November 7, 2020 data cutoff, 27,817 patients were randomized in a 1:1 fashion to receive either the vaccine or placebo with a median follow-up following dose 2 of 7 weeks. These patients were included in the per-protocol efficacy analysis population of those who did not showcase any evidence of SARS-CoV-2 infection before vaccination.
Results from the trial demonstrated that the vaccine efficacy was 94.5% (95% CI, 86.5%-97.8%) in preventing confirmed COVID-19 infection occurring at least 2 weeks following the second vaccine dose. Five cases of COVID-19 were reported in the vaccine cohort vs 90 cases in the placebo cohort.
Additionally, subgroup analyses of the primary efficacy end point demonstrated comparable efficacy end point estimates spanning age groups, racial and ethnic groups, genders, and those with medical comorbidities linked with a high risk of severe infection. Secondary analyses suggested vaccine benefit in the prevention of severe COVID-19 infection, the prevention of the virus following the first dose, and the prevention of infection in those with previous SARS-CoV-2 infection. However, more data are needed to confirm these outcomes.
Data from the final scheduled analysis of the primary efficacy end point of the trial, which a November 21, 2020 data cutoff and a median follow-up of over 2 months following the second vaccine dose, showed a vaccine efficacy of 94.1% (95% CI, 89.3%-96.8%). Eleven cases of COVID-19 were reported in the vaccine cohort vs 185 cases in the placebo cohort; this was consistent with the interim data reported.
When stratified by age, the vaccine efficacy was 95.6% (95% CI, 90.6%-97.7%) in individuals who were aged 18 to 65 years vs 86.4% (95% CI, 61.4%-95.5%) in those over the age of 65 years.
A final secondary efficacy analysis was also found to support the efficacy of the vaccine against severe infection with COVID-19 as defined by the study protocol. Thirty of these cases were reported in the placebo cohort vs none in the vaccine cohort.
No specific safety concerns were reported in the safety data from the interim analysis of 30,350 individuals aged 18 years or older who underwent randomization. Additional follow-up findings from these individuals were shared, at the data cutoff of November 25, 2020; this accounted for a median of 9 weeks of follow-up following the second dose of the vaccine. These data were independently confirmed and concluded to not differ from the safety conclusions reached at the time of the interim analysis.
The most frequent solicited adverse effects with the vaccine included injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%). Additionally, 0.2% to 9.7% of individuals experienced serious adverse effects (SAEs), and these were more commonly experienced following the second dose of the vaccine vs the first. These effects were also noted to be less common in those over 65 years of age vs younger individuals.
The most common unsolicited adverse effect of clinical interest, determined to be potentially associated with the vaccine, was lymphadenopathy (1.1% vs 0.63% in placebo cohort). This was a solicited toxicity after any dose in 21.4% of individuals in the vaccine cohort who were younger than 65 years and in 12.4% of those who were aged 65 years or older; these rates were 7.5% and 5.8%, respectively, in the placebo cohort.
Additionally, the frequency of serious toxicities was low in both arms, both 1.0% in the vaccine and placebo cohorts. The most frequently reported SAEs in the vaccine cohort included myocardial infarction (0.03%), cholecystitis (0.02%), and nephrolithiasis (0.02%); and these effects were noted to be numerically higher in the investigative arm vs the control arm, but no causal relationship between these toxicities and the vaccine has been suggested.
Vaccines and Related Biological Products Advisory Committee Meeting: December 17, 2020. FDA. Accessed December 17, 2020. https://bit.ly/2WmSVx6.