Contribute Try STAT+ Today

Pfizer and partner BioNTech said Monday that their vaccine against Covid-19 was strongly effective, exceeding expectations with results that are likely to be met with cautious excitement — and relief — in the face of the global pandemic.

The vaccine is the first to be tested in the United States to generate late-stage data. The companies said an early analysis of the results showed that individuals who received two injections of the vaccine three weeks apart experienced more than 90% fewer cases of symptomatic Covid-19 than those who received a placebo. For months, researchers have cautioned that a vaccine that might only be 60% or 70% effective. 

The Phase 3 study is ongoing and additional data could affect results.

advertisement

In keeping with guidance from the Food and Drug Administration, the companies will not file for an emergency use authorization to distribute the vaccine until they reach another milestone: when half of the patients in their study have been observed for any safety issues for at least two months following their second dose. Pfizer expects to cross that threshold in the third week of November.

“I’ve been in vaccine development for 35 years,” William Gruber, Pfizer’s senior vice president of vaccine clinical research and development, told STAT. “I’ve seen some really good things. This is extraordinary.” He later added: “This really bodes well for us being able to get a handle on the epidemic and get us out of this situation.”

advertisement

Although it is a bright spot in the battle against the pandemic and a triumph for Pfizer and BioNTech, a German company, key information about the vaccine is not yet available. There is no information yet on whether the vaccine prevents severe cases, the type that can cause hospitalization and death.

Nor is there any information yet on whether it prevents people from carrying the virus that causes Covid-19, SARS-CoV-2, without symptoms. 

Without more information, it’s too early to start predicting how much of an impact the vaccine could make, said Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy.

“I don’t want to dampen any enthusiasm for this vaccine. I just want us to be realistic,” Osterholm said. “For a vaccine to really have maximal impact, it’s going to have to also reduce severe illness and death. And we just don’t know yet.”

Because the vaccine has been studied for only a matter of months, it is impossible to say how long it will protect against infection with the virus. The vaccine does cause side effects, including aches and fevers, according to previously published data. Gruber said that he believed the side effect profile was comparable to standard adult vaccines, but probably worse than Pfizer’s pneumonia vaccine, Prevnar, or a flu shot.

The results have not been peer-reviewed by outside scientists or published in a medical journal, and even Pfizer and BioNTech have been given no other  details about how the vaccine performed by the independent monitors overseeing the study.

Initial supplies of the vaccine, if authorized, will be limited. Pfizer says up to 50 million doses could be available globally. by the end of the year, with 1.3 billion available in 2021. There are also expected to be distribution challenges. The vaccine must be stored at super-cold temperatures, which could make it extremely difficult to deliver to many places. Pfizer has said it is confident those issues can be managed.

Although the estimate of the efficacy of the vaccine could change as the study is completed, it is close to a best-case scenario. That also bodes well for other vaccines in the late stages of testing, including those developed by Moderna, AstraZeneca, and Johnson & Johnson. 

“If that headline really number really holds up, that is huge. That is much better than I was expecting and it will make a huge difference,” said Ashish Jha, the dean of the School of Public Health at Brown University. He cautioned, however, that it is always difficult to evaluate science via press release and that researchers will need to see the full results. He noted that side effects are something to watch, because even if there are no serious long-term complications, people feeling sick for a day or two could lead some to be hesitant to take a vaccine.

“This really bodes well for us being able to get a handle on the epidemic and get us out of this situation.”

William Gruber, Pfizer senior vice president of vaccine clinical research and development

Both Pfizer’s vaccine and Moderna’s use messenger-RNA, or mRNA, technology, which uses genetic material to cause the body to create a protein from the virus; the immune system then recognizes the virus and learns to attack. Other vaccines in the late stages of development use genetically engineered viruses for a similar purpose, or pieces of protein that are directly injected. No mRNA product has ever been approved by regulators.

The story of how the data have been analyzed seems to include no small amount of drama. Pfizer, seeing an opportunity to both help battle a pandemic and demonstrate its research prowess, made decisions that were always likely to make its study the first of a Covid-19 vaccine to produce data — including its decision to have an independent group of researchers, known as a data safety and monitoring board, take an early look at the data in the 44,000-volunteer study before its completion. 

The first analysis was to occur after 32 volunteers — both those who received the vaccine and those on placebo — had contracted Covid-19. If fewer than six volunteers in the group who received the vaccine had developed Covid-19, the companies would make an announcement that the vaccine appeared to be effective. The study would continue until at least 164 cases of Covid-19 — individuals with at least one symptom and a positive test result — had been reported.

Scientists can now design genetic material called mRNA to help us build immunity to certain viruses, including SARS-CoV-2, the coronavirus that causes Covid-19. Find out how mRNA vaccines work in this video. Hyacinth Empinado/STAT

That study design, as well as those of other drug makers, came under fire from experts who worried that, even if it was statistically valid, these interim analyses would not provide enough data when a vaccine could be given to billions of people. 

In their announcement of the results, Pfizer and BioNTech revealed a surprise. The companies said they had decided not to conduct the 32-case analysis “after a discussion with the FDA.” Instead, they planned to conduct the analysis after 62 cases. But by the time the plan had been formalized, there had been 94 cases of Covid-19 in the study. It’s not known how many were in the vaccine arm, but it would have to be nine or fewer.

Gruber said that Pfizer and BioNTech had decided in late October that they wanted to drop the 32-case interim analysis. At that time, the companies decided to stop having their lab confirm cases of Covid-19 in the study, instead leaving samples in storage. The FDA was aware of this decision. Discussions between the agency and the companies concluded, and testing began this past Wednesday. When the samples were tested, there were 94 cases of Covid in the trial. The DSMB met on Sunday.

This means that the statistical strength of the result is likely far stronger than was initially expected. It also means that if Pfizer had held to the original plan, the data would likely have been available in October, as its CEO, Albert Bourla, had initially predicted.

Gruber said that there will not be another interim analysis conducted in the study. He also said that Pfizer’s estimate that it could file for authorization of the vaccine by the third week of November was based on the assumption that the FDA would be willing to accept two-month safety data on half the volunteers in the study as initially planned, when it was to include 30,000 volunteers, not more than 44,000, as is now the case. Those discussions are ongoing.

But Gruber said he now expects that by the time of the planned meeting of the FDA’s vaccine advisory committee in December, the study’s efficacy portion could be completed, having reached 164 cases of Covid-19.

He also emphasized that although there will only be a few months of data from this study, results from earlier studies make him optimistic that immunity from the vaccine will not wane rapidly.

The study has enrolled  43,538 volunteers the companies said, and 38,955 have received their second dose. About 42% of global participants and 30% of U.S. participants have racially and ethnically diverse backgrounds.

Bourla, Pfizer’s CEO, said the results mark “a great day for science and humanity,” in a statement, saying they provide “initial evidence of our vaccine’s ability to prevent Covid-19.” He added: “We look forward to sharing additional efficacy and safety data generated from thousands of participants in the coming weeks.”

Helen Branswell contributed reporting.

  • Uhm, to those thanking the president, I know you’re stubborn so this will go over your head, you remember that he doesn’t believe in science like, at all, right?

  • I do have to wonder about the timing of this announcement. It seems nearly certain to me, especially since some countries were using a kind of ongoing Phase 3 where the research data were available to the government regulatory agencies all along, that Pfizer had preliminary data on efficacy and did not release it.
    Also, the huge numbers of alternative vaccines being developed, and their progress, was kind of blacked out right before the election – granted, those vaccines are being developed in other countries and we can not expect to get all of them as soon as they are produced, but unless we were not allowed to buy them, their existence means the epidemic is going to be pretty much over in six months. It does seems like important news we did not generally see.
    If we had done human challenge testing it is pretty likely we would be mostly vaccinated by now and the epidemic would already be mostly over.

  • How shameful that you did not mention the President of the United States once in this article. He spearheaded the WarpSpeed project to bring this life saving vaccine to market quickly.

    Also, how shameful of you to release this article after the election. Politics. You stink.

    • Pfizer was not in the Warpspeed project. They received no funding from the US Government. However, many other companies are in the program and will produce a successful vaccine. Overall, Warpspeed will be a very successful project.

    • Pfizer was not in the Warpspeed project. They received no funding from the US Government. However, many other companies are in the program and will produce a successful vaccine. Overall, Warpspeed will be a very successful project.

  • Well, well, well…not surprised at all over this news AFTER the election. How convenient!

    • Pfizer was not in the Warpspeed project. They received no funding from the US Government.

  • My feelings on a fast tracked vaccine haven’t changed – though I’m glad it’s not through bill gates foundation… I’ll wait a couple years!

    Congrats Mr president on the successes!

    • How will they know what happens to people if they actually get covid after vaccination? What are the contraindications and the CDC precautions? COVID-19 for some triggers a cytokin storm and for the young and healthy 2 dose regimen seems extra and dangerous. How could they mandate this on people if it does not even block the spread?How many in the study were 18-25 years young healthy?Perhaps it should be only used for those who are high risk, Or be given at a 1 dose regimen for the young followed by an antibody test( remember the vaccine does not block the spread it only makes people less symptomatic) yet many will be forced to get it despite the evidence that many develop very little symptom with the natural virus anyway. Will the government officials and the lawyers and the governors and their families be mandated to get the shot too? For instance why is there no flu shot mandate for government officials?

    • Pfizer didn’t receive money from the federal government for the development of this vaccine in the Warp Speed program. The federal government has a $1.95bn contract for 100 million doses. That’s similar to funding a kickstarter campaign. It gives Pfizer reassurance that there will be a buyer of the product, but they were already in the process of making it.

      To say that president Trump has succcesses (plural?) with Covid is crazy talk. He has been hands off on policy and management since the beginning. He has spread lies and falsehoods (“It will be gone by April”, “We’re rounding the corner”, “Masks have problems too”), and the lack of any cohesive strategy has cost thousands of deaths. Our current situation was avoidable.

Comments are closed.