Covid-19 vaccine: Pfizer and BioNTech will apply for Emergency Use Authorization

Just last week, Pfizer and BioNTech revealed that their experimental Covid-19 vaccine, called BNT162b2, was at least 90 percent effective in an early analysis. On Wednesday, the pharmaceutical and biotech companies reported that their vaccine was even better after it cleared more clinical trial benchmarks for safety and efficacy.

A press release out Wednesday from the two companies reports the results of 170 Covid-19 cases confirmed in their clinical trial pool: Eight in the group that received the vaccine got Covid-19 versus 162 in the placebo group, demonstrating an efficacy of 95 percent.

It follows news this week from a competitor, the vaccine developer Moderna, which reported that its vaccine was 94.5 percent effective in an early analysis.

It’s worth pausing to reflect on where we are: At the one-year anniversary of the first detection in China of the SARS-CoV-2 virus, the pathogen that causes Covid-19, there are now two highly effective vaccine candidates developed at a record pace, both using mRNA, a new vaccine technology that has never before been approved for use in humans.

The announcements are a breathtaking feat of international science, development, collaboration, and public investment. “The study results mark an important step in this historic eight-month journey to bring forward a vaccine capable of helping to end this devastating pandemic,” said Albert Bourla, Pfizer chair and CEO, in a statement.

With 170 detected infections among their 43,661 participants in their phase 3 clinical, Pfizer and BioNTech say they have enough data to apply for an Emergency Use Authorization (EUA) from the Food and Drug Administration, an application they say they will make “within days.”

That means their vaccine could soon start rolling out to people in high-exposure jobs like health workers, possibly before the end of the year.

But there are concerns as well. Pfizer and BioNTech’s latest announcement came, for the second time, in a press release instead of a peer-reviewed paper, although the companies revealed far more about the demographics of their clinical trial than in their first report. BNT162b2 also has some of the most stringent cold storage requirements, demanding temperatures of minus 70 degrees Celsius (minus 94 degrees Fahrenheit) or lower, which may make widespread distribution challenging. The vaccine is also administered in two doses spaced several weeks apart. That adds a huge logistical burden to rolling out the vaccine.

That the clinical trial racked up so many Covid-19 cases among its volunteers so quickly is also a grim reminder of just how fast the disease is spreading right now.

And it will likely take months before any Covid-19 vaccine gets full FDA approval, which would allow the general public to have access to it. Even then, immunizing millions of people in the US against Covid-19 would be an endeavor unprecedented in its speed and scale. So getting through clinical trials is just one step toward ending the pandemic.

Pfizer and BioNTech say their Covid-19 vaccine was safe and effective across a diverse pool of volunteers

Pfizer and BioNTech’s Covid-19 vaccine data so far is still preliminary, but it likely received validation from its Data Safety Monitoring Board (DSMB). This is an independent group of scientists that serves as an intermediary between the pharmaceutical companies and the clinical trial participants to ensure that there is no meddling in the trial. The DSMB meets with the companies at regular intervals to go over their observations of the trial. The fact that Pfizer and BioNTech were able to make this announcement likely means that the committee reported this information to them during an analysis.

“To date, the Data Monitoring Committee for the study has not reported any serious safety concerns related to the vaccine,” the companies reported in their press release. In a separate trial of 8,000 participants, Pfizer and BioNTech reported that the only severe side effects they found that occurred in more than 2 percent of volunteers were fatigue, observed in 3.8 percent of participants, and headache, observed in 2 percent. Surprisingly, the companies found that older adults reported fewer and milder side effects.

Chart showing participant diversity in Pfizer and BioNTech’s Covid-19 vaccine trial.

Pfizer and BioNTech reported that they recruited a diverse pool of volunteers for their Covid-19 vaccine clinical trial.
Pfizer

The trial also recruited a diverse pool of volunteers to see how well the vaccine would work among different populations. About 30 percent of US trial participants came from diverse racial and ethnic backgrounds, and 45 percent were between the ages of 56 and 85. “Efficacy was consistent across age, gender, race and ethnicity demographics,” the companies reported.

The next step for a Covid-19 vaccine: Emergency Use Authorization

During a public health crisis, the FDA can grant an EUA to allow unapproved medical products to treat or prevent serious diseases when there are no adequate alternatives on the market.

The benchmark for an EUA is lower than it is for full approval of licensure. In general, the treatment in question has to have a likely benefit, whereas approval demands evidence of a proven benefit.

However, it’s not just about efficacy. A vaccine has the additional hurdle of a much higher bar for safety than conventional drugs. Since a vaccine has to be distributed to millions of people, including those who are healthy and those who have preexisting conditions, the rate of complications has to be extremely low for both full approval and an EUA.

“The thing people need to keep in mind is the safety data. Do we have enough data on safety at this point that we can go forward with the EUA?” said Jose Romero, chair of the Advisory Committee on Immunization Practices (ACIP), an independent group of health experts that advises the Centers for Disease Control and Prevention on vaccines. “I think the FDA, ACIP, and all of the pharmaceutical companies have said over and over again that safety is paramount as they move forward with full licensure or an EUA for vaccines.”

The burden of approving a Covid-19 vaccine isn’t just on the companies. The FDA also has to be transparent about how it is making decisions. This is especially urgent given that public mistrust of a vaccine stands to be a major hurdle in the effort to contain the Covid-19 pandemic.

Some experts are worried that the FDA damaged its credibility this year with its decisions to grant EUAs to treatments like hydroxychloroquine and convalescent plasma based on weak data, which may have been driven by political pressure from the White House. Some researchers have also criticized the FDA’s full approval of the antiviral drug remdesivir. These decisions have sown doubt about the FDA’s decision-making, and the agency will have to go out of its way to rebuild fragile trust with the public to roll out a vaccine.

How do we decide who gets a Covid-19 vaccine first?

Once an EUA is granted, the Covid-19 vaccine can start to be administered to people outside of the clinical trial. Health workers — doctors, nurses, first responders, medical cleaning staff — are the top priority. “They’re certainly high on the list,” Romero said.

Then the vaccine would be targeted at people who are likely to suffer severe complications from Covid-19, such as people over the age of 65 with other underlying health conditions.

However, there are 18 million health workers in the US alone. There are almost 50 million Americans over the age of 65. More than 10 million Americans are immunocompromised, and more than 100 million US adults have diabetes or prediabetes.

Pfizer and BioNTech said they only expect to have 50 million vaccine doses around the world by the end of the year. And remember this is a two-dose vaccine, so 50 million doses will only protect 25 million people. That means there won’t be enough to go around, even for people at high risk. The companies do expect to have 1.3 billion doses ready in 2021.

ACIP is now putting together its recommendations for how to prioritize people for Covid-19 vaccination. But Romero explained they will also have to consider that there will likely be multiple vaccines on the market shortly. A dozen Covid-19 vaccine candidates are already in phase 3 trials, each with their own unique traits and caveats.

“It’s a little silly to think that all vaccines are going to be ranked the same, because they’ll have different characteristics,” Romero said. “Some vaccines may be better in younger populations; some may be better in older populations.”

The advisory committee will also have to weigh practicality, including the minus 70 degree Celsius storage requirements of the Pfizer-BioNTech vaccine. “Those are going to be very important and impact significantly the logistics of getting these vaccines out and into the arms of recipients,” Romero said. “It’s hard to imagine how you’re going to set up a system to deliver a vaccine that requires storage at minus 70 [Celsius] into the widespread community.”

It’s likely, then, that the BNT162b2 vaccine will be reserved at the outset for health workers who are already working in and around facilities that have the ultra-cold storage systems for this vaccine, or those who are near facilities that are equipped to distribute it. For those in far-flung regions or people who don’t have sophisticated $10,000 freezers nearby, a vaccine with easier storage requirements may be recommended. Moderna’s vaccine, for example, only needs long-term storage at minus 20 degrees Celsius (minus 4 degrees Fahrenheit) and is stable for 30 days between 2°C and 8°C (36°F to 46°F).

Pfizer and BioNTech say they do have a solution for getting their vaccine to places without ultra-cold freezers. “The companies have developed specially designed, temperature-controlled thermal shippers utilizing dry ice to maintain temperature conditions of -70°C±10°C,” according to their press release. “They can be used be as temporary storage units for 15 days by refilling with dry ice. Each shipper contains a GPS-enabled thermal sensor to track the location and temperature of each vaccine shipment across their pre-set routes leveraging Pfizer’s broad distribution network.”

However, even with a green light from the FDA and assembly lines cranking out millions of vaccine vials, developers like Pfizer and BioNTech will still have to keep an eye on the people who received the vaccine to ensure there aren’t any super-rare complications that could arise. “I think it’s important for the public to understand that the process doesn’t end with approval,” Romero said.

For their part, Pfizer and BioNTech said they will continue monitoring their clinical trial participants for two years.

And as these vaccines gradually roll out, people will still have to keep up measures to limit the spread of the virus: wearing masks, maintaining social distance, keeping up good hygiene. Until there is widespread vaccination, Covid-19 will remain dangerous and deadly, and the steps taken to mitigate it now will ensure a smoother and more effective campaign to halt the pandemic.

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