According to briefing documents released Tuesday ahead of an FDA advisory panel meeting on December 17, agency staff concluded that the efficacy of Moderna's candidate COVID-19 vaccine mRNA-1273 at preventing coronavirus infections 14 days after a second dose was consistent, at 94.1%, with results obtained from the interim analysis of a Phase III study. However, the reviewers noted that the vaccine's effectiveness among people 65 years and older "appears to be lower" than in younger adults 18 to 64, where rates were 86.4% and 95.6%, respectively, and also comes in below the efficacy seen at the interim analysis, which was estimated at 100% based on a total of 15 cases of COVID-19.
The briefing documents come less than a week after the FDA granted emergency-use authorisation to Pfizer and BioNTech's BNT162b2 for use in people aged 16 and older, making it the first COVID-19 vaccine in the US. The first doses of BNT162b2 have already been delivered as part of the country's nationwide rollout. Moderna is seeking emergency-use authorisation for its vaccine, which is mRNA-based like BNT162b2, for people 18 years and older.
According to people familiar with the matter, cited by The New York Times, the FDA intends to grant emergency authorisation for use of mRNA-1273 the day after the advisory committee meeting. In August, the US government placed an initial order for 100 million doses of mRNA-1272 at a cost of $1.5 billion, and last week bought an additional 100 million doses to be delivered in the second quarter of 2021. The US also retains the option to purchase up to 300 million doses of the vaccine as part of its purchase agreement.
According to FDA reviewers, the efficacy of mRNA-1273 was greater than 93% in the group of study participants with or without prior infection, although they said it was difficult to interpret the data for those with positive SARS-CoV-2 status at baseline as this was "limited by the small sample size and case numbers in this subgroup." Meanwhile, "efficacy outcomes across demographic subgroups were consistent with the efficacy seen in the overall study population," agency staff said. In terms of severe disease, there were 30 cases recorded at the time of the interim analysis, including nine hospitalisations, all being in the placebo group. The FDA noted that all 11 cases of severe COVID-19 occurring 14 days after the second dose of mRNA-1273 were in the placebo group, although one may have occurred in a vaccine recipient as well. Agency staff said this particular case did not meet criteria for the protocol-specified case definition.
Meanwhile, FDA reviewers said the vaccine efficacy rate was 80.2% in the modified intent-to-treat population who had received one dose of mRNA-1273 at the time of the interim analysis. However, they cautioned that the findings so far "cannot support a conclusion on the efficacy of a single dose of the vaccine, because the numbers of participants and time of observation are limited."
The FDA highlighted no additional safety concerns with mRNA-1273, with injection-site pain, fatigue and headache being the most common solicited adverse reactions. The documents showed that grade 3 fatigue was reported by 9.6% of people given mRNA-1273, versus 1.3% of placebo recipients. Meanwhile, the rates of grade 3 injection-site reactions were 9.1% in the vaccine group, compared to 0.9% in the placebo group, while headache was reported in 5.5% of those given mRNA-1273, versus 2.2% in the placebo arm. Agency staff said proportions of participants experiencing severe adverse events, death, and withdrawals due to adverse events were "balanced" across the study groups.
However, the reviewers did highlight a "small imbalance" in the number of participants reporting Bell's palsy, with three cases occurring among vaccine recipients, including one deemed a serious adverse event (SAE), and one in the placebo group. The SAE case occurred 32 days after vaccination and was reported as "resolving." The two other instances of Bell's palsy among mRNA-1273 recipients occurred 28 days and 22 days after vaccination, with one case resolved and the other still ongoing at the time of the safety report. "Causality assessment is confounded by predisposing factors in these participants," FDA staff said, but "considering the temporal association and biological plausibility, a potential contribution of the vaccine to the manifestations of these events of facial palsy cannot be ruled out."
In briefing documents for Pfizer and BioNTech's vaccine last week, agency staff said there had been four cases of Bell's palsy among BNT162b2 recipients, but indicated that the frequency of this particular safety finding was "consistent with the expected background rate in the general population."
Meanwhile, Moderna also disclosed new data that was not available at the time of its emergency-use authorisation application, saying the finding potentially supports the efficacy of mRNA-1273 against asymptomatic infection. The company said it collected nasopharyngeal swabs for SARS-CoV-2 prior to the second injection, finding that 14 study volunteers in the vaccine group and 38 in the placebo group had evidence of infection at the second dose, but no COVID-19 symptoms. "There were approximately [two-thirds] fewer swabs that were positive in the vaccine group as compared to the placebo group at the pre-dose 2 time-point, suggesting that some asymptomatic infections start to be prevented after the first dose," Moderna said.
For related analysis, see ViewPoints: mRNA reigns supreme in COVID-19 vaccine race.
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