Pfizer's and BioNTech's COVID-19 Vaccine is Highly Effective, Research Shows

“I’ve been in vaccine development for 35 years,” - William Gruber,
Based on its initial data, pharmaceutical company Pfizer said Nov. 9 that its experimental vaccine was more than 90 percent effective in preventing covid-19. (Reuters)

On Monday, Pfizer and partner BioNTech said their Covid-19 vaccine was highly successful, exceeding expectations with outcomes that are likely to be met with cautious optimism and relief in the face of the global pandemic.

The vaccine is the first to produce late-stage data in the United States to be tested. An early review of the findings found that people who received two vaccine doses three weeks apart experienced more than 90% fewer cases of symptomatic Covid-19 than those who received placebo, the companies said. Researchers have warned for months that a vaccine could be only 60 per cent or 70 per cent effective.

The Phase 3 analysis is ongoing, and the findings may be influenced by additional data.

Companies will not apply for an emergency authorization to administer the vaccine in compliance with the Food and Drug Administration's guidelines until they hit another milestone: when half of the patients in their trial have been monitored for any safety problems for at least two months after their second dose. In the third week of November, Pfizer plans to surpass the mark.

“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.”

While Pfizer and BioNTech, a German corporation, are a bright spot in the fight against the pandemic and a victory, key information about the vaccine is not yet available. There is no information yet about whether the vaccine, the kind that can cause hospitalization and death, prevents serious cases.

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

Michael Osterholm, director of the Center for Infectious Diseases Research and Policy at the University of Minnesota, said that without further details, it is too early to begin predicting how much effect the vaccine will have.

“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.”

Since the vaccine has only been tested for a couple of months, it is difficult to tell how long it can protect against virus infection. According to data previously released, the vaccine does cause side effects, including aches and fevers. Gruber said that he assumed that the side effect profile was similar to that of normal adult vaccines but potentially worse than that of a Pfizer vaccine for pneumonia, Prevnar, or flu shot.

The findings were not peer-reviewed by outside scientists or reported in a medical journal and no further specifics were given to Pfizer and BioNTech on how the vaccine was carried out by the independent research supervisors.

There will be limited initial supplies of the vaccine if approved. Pfizer estimates there could be up to 50 million doses available worldwide. With 1.3 billion usable in 2021, by the end of the year. Distribution problems are also expected to occur. It is important to store the vaccine at super-cold temperatures, which could make a distribution to many locations extremely difficult. Pfizer has said it is optimistic that it is possible to handle these problems.

While as the research is completed, the estimation of the effectiveness of the vaccine could shift, it is similar to a best-case scenario. In the late stages of testing, that also bodes well for other vaccines, including those produced 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.

Both the Pfizer and Moderna vaccines use messenger-RNA, or mRNA, a technology that uses genetic material to induce the body to develop a virus protein; then the immune system recognizes the virus and learns to fight. In the late stages of development, some vaccines use genetically modified viruses or pieces of protein directly injected for a similar purpose. Regulators have never approved any mRNA product.

No small amount of drama seems to involve the story of how the data has been processed. Seeing an opportunity to both help combat a pandemic and demonstrate its scientific ability, Pfizer 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 impartial group of experts, referred to as data protection and monitoring board, take an early look at the data in the 44,000-volunteer study before its completion.

The first study was to occur after Covid-19 had been contracted by 32 volunteers, including those who obtained the vaccine and those on placebo. If Covid-19 was produced by less than six volunteers in the community that received the vaccine, the companies will make an announcement that the vaccine appeared to be successful. The research will continue until at least 164 Covid-19 cases were registered, individuals with at least one symptom and a positive test result.

This design of the report, as well as that of other drug manufacturers, came under fire from experts who were worried that, even if statistically accurate, these interim studies would not provide adequate evidence when billions of people might be given a vaccine.

Pfizer and BioNTech shared a surprise in their announcement of the results. The companies said they had agreed not to perform the 32-case study "after a conversation with the FDA." Instead, after 62 cases, they intended to perform the analysis. But there had been 94 cases of Covid-19 in the sample by the time the proposal had been formalized. How many were in the vaccine arm is not known, but it would have to be nine or less.

In late October, Gruber said Pfizer and BioNTech had agreed they wanted to withdraw the 32-case interim review. The companies agreed at that time to avoid making their laboratory confirm cases of Covid-19 in the report, instead of keeping samples in storage. The FDA knew about this decision. Discussions ended between the organization and the businesses, and this past Wednesday, testing began. There were 94 cases of Covid in the trial when the samples were examined. On Sunday, the DSMB met.

This means that the statistical strength of the outcome is likely to be much greater than originally expected. It also means that if Pfizer had kept to the original schedule, as its CEO, Albert Bourla, had initially expected, the data would likely have been available in October.

Gruber said that the report would not carry out any further interim review. He also claimed that Pfizer's prediction that it should file for vaccine authorization by the third week of November was based on the assumption that, as originally intended, the FDA would be prepared to approve two-month safety data on half of the study volunteers when it was to include 30,000 volunteers, not more than 44,000, as is now the case. These conversations are continuing.

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

He also stressed that while data from this study would only remain for a few months, findings from earlier studies make him hopeful that immunity from the vaccine will not decline rapidly.

43,538 volunteers were enrolled in the study, and 38,955 were given their second dose. Around 42 per cent of global respondents and 30 per cent of U.S. participants have backgrounds that are culturally and ethnically diverse.

In a statement, Bourla, CEO of Pfizer, said the findings mark a great day for science and humanity, saying they provide initial proof of the ability of our vaccine 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.”