In briefing documents released Tuesday ahead of an FDA advisory committee meeting on December 10, agency staff said that efficacy data submitted by Pfizer and BioNTech in support of BNT162b2 are “consistent” with recommendations previously detailed in guidance on the emergency-use authorization (EUA) of COVID-19 vaccines. The regulator also noted that safety information on BNT162b2 was “adequate for review and to make conclusions…in the context of the proposed indication and population.”
The companies filed an EUA request to the FDA last month shortly after BNT162b2, which is administered as two doses given 21 days apart, demonstrated an efficacy rate of 95% at the final efficacy analysis of a Phase 3 study in which approximately 36,600 participants were randomized to receive the vaccine or placebo. The analysis was based on 170 cases of COVID-19 and measured seven days after the second dose.
‘Consistently robust’ efficacy
The FDA documents noted that efficacy outcomes were “consistently robust” in the trial, being at least 93%, across demographic subgroups, and 94% in those over the age of 55. Agency reviewers said that among all study participants, regardless of evidence of infection before or during the vaccination, 50 cases of COVID-19 occurred in the BNT162b2 group after one dose of the vaccine compared with 275 cases for placebo, for an estimated efficacy of 82%. However, agency staff suggested more data would be needed to assess the potential of a single-dose of the vaccine, as the efficacy after the first dose and before the second was around 52%. Meanwhile, effectiveness against severe COVID-19 after the first dose was 88.9%, dipping to 75% at least seven days after the second, based on one case recorded in the BNT162b2 group and four for placebo.
The study’s primary endpoint was evaluated in individuals without prior evidence of COVID-19 disease, although FDA reviewers said that available data, “while limited, do suggest that previously infected individuals…could benefit from vaccination.” They noted that “very few cases” of confirmed COVID-19 occurred among participants with evidence of infection prior to vaccination, though more of those that did were in the placebo group than the vaccine arm.
Frequent, mostly mild side effects
The FDA said side effects after vaccination were “frequent and mostly mild-to-moderate” in nature, with injection-site reactions, fatigue and headache being the three most common, while others included muscle pain, chills, joint pain and fever. Severe adverse reactions were more frequent after the second dose, and generally happened less often in adults over 55 than in younger participants, at rates of 2.8% or less and 4.6% or less, respectively.
In regards to adverse events “possibly related” to BNT162b2, FDA reviewers noted that lymphadenopathy was reported in 64 vaccinated subjects, compared to six in the placebo group. These cases lasted about 10 days on average, with 11 events ongoing at the time of the data cut-off, agency staff said. Bell’s palsy was also reported by four vaccine participants, with three of these cases occurring from dose one through one month after dose two, although the FDA noted that this frequency is “consistent with the expected background rate in the general population.” Agency staff found “no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events, including other neurologic, neuro-inflammatory, and thrombotic events, that would suggest a causal relationship to BNT162b2 vaccine.”
The reviewers also said there is “currently insufficient data” to draw conclusions about the safety of the vaccine in people under 16 years of age, pregnant women and immunocompromised individuals. Meanwhile, there were a total of six deaths that occurred in the reporting period, including two in the vaccine group. One vaccinated participant, who had baseline obesity and pre-existing atherosclerosis, died three days after receiving the first dose of BNT162b2, while the other experienced cardiac arrest 60 days after the second dose and died a few days later.
US approval expected ‘imminently’
Jefferies analyst Michael Yee said the FDA documents were “very simple and straightforward, which we think will lead to approval imminently.” Meanwhile, Pfizer CEO Albert Bourla said that although he expects the advisory committee meeting to be “very intense… I think they will vote ‘yes’ given the strength of the data.”
The mRNA-based vaccine received its first EUA last week when regulators in the UK granted a temporary authorization. The European Medicines Agency is also evaluating the vaccine, having started a rolling review of BNT162b2 in early October.