Contribute Try STAT+ Today

Scientists at the Food and Drug Administration endorsed the efficacy and safety of the Covid-19 vaccine from Pfizer and BioNTech in detailed documents released Tuesday, setting the stage for an emergency authorization as early as this week.

The documents are a prelude to a Thursday meeting of outside experts, which is likely the final step before the FDA grants an emergency use authorization, or EUA. The FDA reviewers state that the two-dose vaccine was “highly effective” in preventing symptomatic Covid-19, and that the data “suggest a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an EUA.” The data also suggest that the two-dose vaccine may begin preventing some Covid-19 cases after the first dose.

But the document dump — 53 pages of documents from FDA reviewers and another 92 from Pfizer and BioNTech — also provides new information about the side effects of the vaccine (most patients have sore arms and headaches). And it sets up topics for discussion about the vaccine’s efficacy, including what potential rare side effects regulators and the manufacturers should watch for, and how well the vaccine protects against severe Covid-19.

advertisement

At Thursday’s meeting of the Vaccines and Related Biological Products Advisory Committee, the agency will seek the opinions of outside experts who will vote on whether the benefits of the Covid-19 vaccine, BNT162b2, outweigh its risks. Though the FDA does not have to follow the recommendations of these panels, it usually does.

A similar committee will convene on Dec. 17 to consider the emergency use of a similar vaccine developed by Moderna, working with the National Institutes of Health.

advertisement

An EUA is not normally required to meet the same stringent requirements as an approval. But because a vaccine could be given to hundreds of millions of people, the FDA is following its normal, and famously tough, advisory committee process.

Pfizer and BioNTech first announced interim data on Nov. 9 indicating that their vaccine can prevent more than 90% of symptomatic Covid-19 infections. On Nov. 18, the companies released the main analysis of their study in a press release. There were 170 cases of symptomatic Covid-19 in the 44,000-patient study, in which patients were randomly assigned either to receive the vaccine or a placebo. Of these, 162 were in the placebo group, while just eight were in patients who received the vaccine. That means that the vaccine reduced the risk of infection by 95%.

The FDA briefing documents contain a much deeper look at the 170 Covid-19 cases Pfizer reported in November, but no information about cases that have occurred in the study since this original analysis occurred.

It’s worth stepping back to take a look at the data plotted on a graph, which is included in this story. The blue line on the graph represents Covid-19 cases in the vaccine group, the red one Covid-19 cases in the placebo group. The degree to which the vaccine prevents infections, seen this way, is unmistakable.

vrbpac/pfizer
Courtesy Pfizer

The FDA reviewers also argue that analyses suggested the vaccine prevents Covid-19 following the first dose, meaning that even if people miss their second dose they may get some protection from transmission. However, the FDA scientists cautioned the results “cannot support a conclusion on the efficacy of a single dose of the vaccine” because there is not enough data.

One topic of discussion will likely be around how well the Pfizer vaccine prevents severe Covid-19. In Moderna’s study, there were 30 cases of severe disease, none in the vaccine arm. In Pfizer’s, there were 10, with one in the vaccine arm. But both Pfizer and the FDA seem to argue in their briefing documents that perhaps that should not count against this vaccine.

“The vaccine recipient who had severe Covid-19 disease met the severe case definition because oxygen saturation at the Covid-19 illness visit was 93% on room air,” the FDA reviewers wrote. That number is below normal, but just barely. “The subject was not hospitalized, did not seek further medical care, and did not have risk factors for severe disease.”

The briefing documents also provide the best examinations so far at the common and more severe potential side effects from this vaccine. Injection site reactions occurred in 84.1% of recipients, fatigue in 62.9%, headache in 55.1%, chills in 31.9%, and fever in 14.2%. Severe reactions occurred in 2.8% of volunteers over the age of 55 and in 4.6% of those under 55; younger patients often have stronger reactions because they have stronger immune systems.

Serious adverse events, which are worse than severe reactions, occurred at the same low rate (just half a percent) in the vaccine or placebo arms. There were four cases of Bell’s palsy, a temporary weakness or paralysis, in the vaccine arm and none in the placebo arm, and the FDA recommends following vaccine recipients specifically for this side effect. There were also 64 cases of lymphadenopathy, a swelling of the lymph nodes,  in the vaccine group versus six in the placebo group.

Patients in the trial remain unaware of whether they received the vaccine or the placebo. Pfizer plans to offer patients who received the placebo a vaccine if it is covered by an emergency use authorization, but the FDA has urged companies to keep patients blinded and not offer placebo patients the vaccine for as long as possible. The FDA recognizes Pfizer’s plan in its briefing document, but the topic of when placebo patients get the vaccine could be something the committee discusses.

Pfizer and BioNTech have said they will be able to manufacture 50 million doses of their vaccine, enough for 25 million people, by the end of December. The Centers for Disease Control and Prevention expects that 40 million doses of vaccine will be available in the U.S. in 2020, with 25 million coming from Pfizer and 15 million from Moderna if its vaccine is authorized this month.

The U.S. government has agreed to acquire 100 million doses of each vaccine with the option to purchase 900 million more of the two vaccines combined. It’s not clear how quickly the companies can manufacture enough to vaccinate all 330 million Americans, however on Monday a federal official, speaking on background during a briefing, estimated the U.S. expects to be able to vaccinate all willing Americans by the end of the second quarter of 2021.

Pfizer and BioNTech hope to manufacture up to 1.3 billion doses in 2021 to serve the entire world. Moderna said it is on track to produce 500 million to 1 billion doses of its vaccine globally in 2021.

The 44,000-patient clinical trial enrolled a diverse patient population in terms of race and ethnicity, age, and underlying health conditions. About 26% of participants were identified as Latino and 10% as Black, with the study evenly split between men and women. There did not appear to be any difference in the vaccine’s effect based on the gender or race of recipients, nor was there any difference in recipients with conditions like obesity and hypertension that can be predictive of how well patients do when they get Covid-19.

Adam Feuerstein, Damian Garde, and Helen Branswell contributed reporting.

This story was updated to say that injection site reactions occurred in 84.1% of vaccine recipients.

  • There have been two deaths from the Pfizer vaccine. The FDA will approve it anyway. How many people would have to die before the FDA pulls the vaccine from further distribution? The potential for harm by adverse effects as listed by the FDA is more than concerning. Do the benefits outweigh the risks? I’m not at all sure.

  • Personally, I am curious to see what happens between 120- 180 days post treatment, and 180-365 days post treatment. I would also prefer to know, how many of those 44,000 had Covid-19 antibodies in their blood at Dose 1, and how many had Covid-19 antibodies at 120-days; essentially how many people had Covid, but did not report symptoms? The 170 people, in my view is still a small sample size, without knowing the background of those specific people and the larger group. Or does the dose only reduce symptomatic infections, and the people can still spread? What is their viral spread? Many more questions remain.

    • Hats off to Pfizer for fronting its own money (not Govt $) to conduct this groundbreaking trial.

      Trials can be sized to account for variables other than just a positive outcome so I expect further data is coming. Having said that having antibodies won’t get people off the hook for wearing masks and social distancing far into 2021.

      I’m 60 and remember getting the Polio vaccine in the early 1970s. Everyone did it because of a SOCIAL RESPONSIBILITY to their neighbors and Country. The BENEFITS of the Covid vaccine outweighs the RISKS and everyone should pull up their big boy panties and GET THE SHOT.

  • That graph on cumulative infections over time in the two arms is fantastic news. Most of the cases in the vaccine arm occurred in the first 14 days (which is before the 2nd dose, and likely while the immune system was still reacting to the 1st dose). After the 14 days, the two graphs diverge considerably.

    Also, they should just be honest about the side effects. If some number of people are going to have a rough reaction, just be open about it. Don’t let the anti-vaxxers throw more fuel on their fire.

    • Emilio is right. An injection site reaction is usually recorded as “pain or discomfort at the injection site”. Study participants are required to report any and all concerns and they are recorded as such.

      I drove my car for 8 hours yesterday and today I have pain in my left calf. If I was a study participant I’d report that “side effect” at a follow up visit to the study coordinator.

      The Pfizer vaccine benefits outweigh the risck or inconvenience to probably 95% of any population. It’s our moral responsibility to get this shot.

  • “Injection site infections occurred in 84.1% of recipients” – is that right? I’ve never had an infection after a jab of any sort.

Comments are closed.