As soon as pharmaceutical company Pfizer issued a press release on the morning of November 9th indicating that their Covid-19 vaccine candidate appears to have an efficacy rate of more than 90 percent, the reaction tended to go in one of two directions: The first was sheer excitement. We had just come out of a weekend where we learned of Joe Biden’s projected election win, and news of a Covid vaccine significantly more effective than initially thought felt like the cherry on top of the Four Seasons Total Landscaping sundae.
On the other end of the spectrum were those who said that there were still too many questions left unanswered, and pointed to the fact that the news came via a Pfizer press release — not a peer-reviewed journal article — and therefore shouldn’t be taken seriously. Others highlighted the logistical challenges of manufacturing, transporting and storing the vaccine at minus-80 degrees Celsius. But what, if anything, does Monday’s announcement from Pfizer actually tell us? Is this a major breakthrough, or merely marketing? Here’s some background and context that should help.
What did we learn from the Pfizer announcement?
To start with, as the Pfizer news release notes in its headline, this is the first interim analysis: not the final results of the study. “It’s kind of like a first peek,” says Dr. Wilbur Chen, the chief of the adult clinical studies section within the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine (UMSOM), adding that the findings in the Pfizer announcement come a little more than halfway through the analysis of the clinical trial’s data. Chen and his colleagues are particularly familiar with the research: In May, the Center for Vaccine Development became one of the four testing U.S. sites that conducted phase-one of the Pfizer Covid vaccine clinical trials, and, more recently, phase-three of the Moderna vaccine trials.
So if the analysis has only reached its midpoint, why is this such big news? Part of the reason, according to Chen, is that so far, the data that have been positive, and researchers hope that it continues to go in that direction. The other part is strikingly similar to what we’ve been going through over the past week. “It’s like with the vote counting: It’s almost done, but not completely done, but there’s a point where you can really get the sense of which way the votes are going,” Chen tells Rolling Stone. “Continuing to count the votes is an important thing to have complete closure. But having that early look gives you the ability to predict where everything is going, and by that time it’s not going to be swaying significantly one way or the other.”
Those pointing to the fact that this information coming from a company press release and not a peer-reviewed journal article are not wrong. Academic peer-review is a crucial step in the research process, and involves other experts in a field evaluating, improving, and validating the data and methodology of a study. The Pfizer release isn’t a peer-reviewed journal article, but it’s also not even the complete analysis of the study’s data — nor does it pretend to be. “Despite it being a release from the manufacturer, there have been many federal agencies and academic organizations involved in doing the study,” Chen says. “So I think that we can trust this early information, but it is early information.”
There is a peer-reviewed journal article in the works, but it’s not required as part of the Food and Drug Administration (FDA) approval process. “The FDA will be reviewing the raw data — they don’t wait for making decisions on licensure or emergency use authorization based on the publication [of a peer-reviewed journal article],” Chen explains. While the resulting article will be an important high-level summary of the trial’s findings, the FDA will use far more detailed data when considering Pfizer’s application.
What don’t we know at this point?
Pfizer may be halfway through analyzing the data from the Covid vaccine clinical trials, but there’s still plenty we don’t yet know, including the final efficacy rate. It’s a little more than 90 percent now, but that’s an estimate, Chen explains.
There are also several other crucial pieces to the vaccine puzzle that won’t be put in place until more time has passed. For example, it is not yet known how long the vaccine will protect someone against the novel coronavirus — whether it’s a few months, a year, or more. “We also won’t know if it helps stop transmission among asymptomatic people,” Chen says. “That’s not really answered in this study, because it was not designed to do that.”
At this stage, it’s also unclear whether the Pfizer Covid vaccine candidate protects against the severity of the infection, which can be mild, moderate, or severe enough to require hospitalization and cause death. But according to Chen, at the very least we do know that the vaccine can prevent mild cases of the symptomatic illness. “So presumably that means that if you can prevent that, then you can prevent subsequent hospitalization and/or death,” he adds.
What does the >90% efficacy rate mean?
The big headline from the Pfizer announcement is that the estimated efficacy rate of their Covid vaccine is more than 90 percent — but what exactly does that mean? While, as Chen pointed out, there are still unknowns, like whether the vaccine can prevent asymptomatic transmission, he says that the high efficacy rate still tells us a lot, because symptomatic cases of Covid — which lead to hospitalizations, deaths, or long-term symptoms — are a major factor in determining the public health value of a vaccine. And though the >90% efficacy rate is an estimate, Chen says that the final figure is likely to be similar. For comparison, the flu vaccine is typically between 40 and 60 percent effective, and two doses of the measles, mumps, and rubella (MMR) vaccine are 97% effective against measles and 88 percent effective against mumps.
According to Dr. Kirsten Lyke, a co-principal investigator on the first phase of the Pfizer Covid vaccine trial and the director of the malaria vaccine and challenge unit at the Center for Vaccine Development at UMSOM, even though the >90% efficacy rate indicated in Pfizer’s interim analysis isn’t yet the full picture, it has exceeded the team’s expectations. “[The early results] are better than anticipated. It’s super thrilling,” she tells Rolling Stone. “Most of us thought — or hoped — [the efficacy rate] would be better than the threshold of 50% that the FDA floated as the benchmark of criteria for submission [for approval], but no one anticipated early results of 90% efficacy. Though we do also want to be cautious, because we don’t yet know its longevity.”
As far as how effective the vaccine could be on future mutations of the virus, Lyke says so far, the mutations that researchers have identified don’t appear to affect the full spike protein of the coronavirus. “I don’t know, over the long-haul, how that’s going to go, but right now in watching what’s going on with mutations, we haven’t seen anything that would derail the vaccine yet.”
What might the timeline for the rollout of the vaccine look like?
It’s still too early to know when, exactly, the Pfizer (or any Covid) vaccine will be widely available to the public, but in a recent interview with CNN, Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, predicted that it could be as soon as April 2021. So while we’re getting close, we’re not quite to the finish line yet. Lyke says that we should have results of Pfizer’s second interim analysis as well as two months of safety data — meaning information on how the participants tolerated the vaccine — within a few months. From there, the data will be sent to the FDA, though, as Lyke points out, additional safety data will continue to be collected from participants over the next two years.
What does this tell us about the other vaccine candidates?
Both the Pfizer and Moderna Covid vaccine candidates use messenger (m) RNA, which is essentially a piece of genetic code that instructs cells to make portions of the coronavirus spike protein. The aim of this vaccine is tricking our bodies into thinking that it’s seeing the virus and producing antibodies to fight Covid-19, when it’s really just reacting to the spike protein. So are the early Pfizer results promising for Moderna and other ongoing trials? “The Moderna [vaccine] is very similar [to the Pfizer vaccine] in terms of its actual construct,” Lyke explains. “So, if it works for Pfizer there’s no reason that it shouldn’t work for Moderna.”
The indication that the vaccine is able to stimulate a good immune response bodes well not only for Moderna, but also for other vaccine candidates, Lyke says, including those from Johnson & Johnson and AstraZeneca. Unlike the mRNA-based Pfizer and Moderna vaccines, the ones Johnson & Johnson and AstraZeneca are testing use engineered versions of an adenovirus, a type of virus that typically causes the common cold. While both companies previously paused their research over safety concerns — which not at all unusual in clinical trials — both are now back up and running,
In terms of safety, Lyke says that with a combined total of nearly 75,000 participants in both the Pfizer and Moderna trials, each of whom received two doses of the vaccine, the fact that there haven’t been any major safety signals is promising. “That’s pretty strong reliability,” she says. “We can stimulate a really good immune response, so it’s looking positive that that’s going to hold true for other types of vaccines.”
But aside from the time it will take to manufacture the number of vaccines necessary to make a significant impact on public health, there are other logistical challenges with Pfizer’s vaccine, stemming from the fact that it must be stored at minus-80 degrees Celsius. “One of the critical pieces of preserving the cold chain, which sounds like it would be easy, but this particular vaccine needs to be in ultra-frigid conditions,” Lyke explains. “I mean every, CVS in America doesn’t have this kind of cold chain, so it’s definitely going to take some ingenuity to make some sort of storage devices that will be shippable to every facility that’s capable of giving vaccines.” But it’s not a matter of starting from scratch: Lyke says that Pfizer has been working on the logistical end of Covid vaccine manufacturing for months. In addition, companies outside of the pharmaceutical industry — including Corning, which is manufacturing glass vials able to withstand the incredibly low temperatures required to store the vaccine — have been ramping up production of the other necessary components of the cold chain.
Ultimately, though, Lyke believes that like the countless other challenges of developing a vaccine during a pandemic at record speed, this is another that can be faced. “It’s not insurmountable,” she says. “We’ve made a vaccine, tested it with 44,000 people, and have results in seven months, so I’m not really all that concerned about it.”