Another step forward for Biontech and Pfizer’s Covid-19 vaccine

The first in-depth look at the data behind the leading Covid-19 vaccine raises few red flags ahead of a US advisory panel later this week.

The UK raised eyebrows last week with its speedy review of BNT162b2, Biontech and Pfizer’s Covid-19 vaccine, but it seems that the US will not be far behind. The FDA’s review of the data behind the submissions, published today, raises few serious concerns, setting the project up for emergency use authorisation in the days following Thursday’s advisory committee.

The briefing documents for the adcom allow the first in-depth look at the safety and efficacy data generated so far. New nuggets of information include impressive effectiveness across a number of subgroups, albeit with the caveat that low numbers prevent firm conclusions from being drawn. And while a couple of safety imbalances deserve to be watched, reviewers look likely to consider BNT162b2’s benefits to outweigh the risks.


Given the speed with which these vaccines have been developed, and the novelty of the mRNA-based technology upon which BNT162b2 is based, safety was always going to be the big focus when more data became available. And the take home message from the FDA's review is pretty encouraging.

Safety data so far “suggest a favourable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA”, according to the documents released today. It is important to remember that this conclusion is based on a median of only two months of follow-up after the second dose, in 38,000 subjects.

The majority of people (84%) had a sore arm, while fatigue (62.9%), headache (55.1%), muscle pain (38.3%), chills (31.9%), joint pain (23.6%) and fever (14.2%) were the other commonly occurring issues.

Severe adverse reactions occurred more commonly in younger participants, at a rate of up to 4.6%, than in those of 55 years of age or older, where the rate was 2.8%. Around 1% of younger patients graded the injection site pain as severe, for example, compared with less than 0.5% of the 55+ group.

The FDA highlighted four cases in the vaccine group of Bell’s palsy – a sudden but temporary weakness in facial muscles – whereas no cases were detected in the placebo arm. Still, the agency noted that these occurred at a frequency expected in the general population, and while there is no clear basis to conclude a causal relationship, further surveillance was recommended.

Another issue was higher rates of abnormally swollen lymph nodes, or lymphadenopathy, which could plausibly be related to vaccination, the FDA said. This was reported in 64 cases in the vaccine group, with six in placebo.

Further serious events with imbalances included appendicitis, heart attack and cerebrovascular incidents, but these occurred at very low rates.


Detailed efficacy data also contained few areas of concern for the regulator. A look at cumulative incidence curves shows that the vaccine appears to kick in 14 days after the first dose, and remains protective for the two months shown here. Duration of effect remains one of the burning questions still to answer.

A breakdown of the results by dose shows that efficacy between dose one and dose two is 52%; as previously disclosed, efficacy rose to 95% seven days after the second dose. Whether one dose might be enough is likely to be a subject of debate for the advisory committee, although the FDA concluded that there was not enough data on a single shot regimen to answer this.

Source: FDA briefing documents

Interestingly, the FDA noted that while the data are limited, the results suggest that previously infected individuals could benefit from vaccination. Around 3% or just over 1,000 participants had evidence of prior infection, among whom only 19 cases of Covid-19 were recorded – nine in the placebo group, and 10 in the vaccine group, though only one of these occurred more than seven days after the full dose. The placebo group attack rate was 1.3% for patients with and without evidence of prior infection.

The FDA also notes that vaccine efficacy was “uniformly high” across subgroups, but that several cohorts contained too few Covid-19 cases to draw firm conclusions. This will no doubt form a major plank of research for the future, to ensure that vulnerable groups are protected.

Whether a vaccine can prevent severe Covid-19 is hugely important, and four such cases occurred in subjects who received both injections (one in the active arm and three in the placebo arm), and 10 after the first dose (one in active and nine in placebo). Again, the FDA notes that the number of severe cases was small, limiting conclusions; however “the case split does suggest protection from severe Covid-19 disease,” the reviewers wrote.

Comments on the conduct of the trial in terms of the balance of demographics and high-risk groups threw up no sticking points for the FDA. All of this will be discussed at greater length on Thursday by the assembled of panel of experts, but only one outcome is expected.

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