Pfizer/BioNTech’s New Vaccine Is Safe and Effective
Results of Phase III trials of the BNT162b2 RNA vaccine are public…
The COVID-19 pandemic has been devastating communities around the world for the greater part of a year now. Tens of millions are affected globally, and millions have been infected here in the U.S. causing three hundred thousand deaths as of mid-December, 2020.
Perhaps the most dramatic news of the year is the extremely rapid development of a novel RNA-based vaccine using the technology of a small Germany biotech company called BioNTech, who partnered with the global pharmaceutical giant, Pfizer.
The U.K. had already approved the drug and started vaccinations, and this week the U.S. Food and Drug Administration (FDA) has finally also given authorization for emergency use. The following is a review of the Phase III clinical study on which the approval decisions were made.
1. The verdict…
The new Pfizer/BioNTech RNA-based vaccine is 95% effective in preventing COVID-19 in patients who were 16 years old or older. The new drug is as safe as other viral vaccines at the two-month period, which is the median duration collected so far.
If you read no further, the main message is that the Pfizer/BioNTech vaccine BNT162b2 is safe and effective based on the gold standard, a randomized, double-blind, placebo-controlled three-phase clinical trial.
This article is my personal assessment and applies only to the Pfizer/BioNTech vaccine. I have not reviewed others (such as Moderna’s vaccine or others, similar or not).
If you are comfortable reading clinical studies, you can read the report in the New England Journal of Medicine (NEJM) here. If not, please read on.
2. The risks…
What follows is my own very brief list of risks, none of which I believe rise above the risk of COVID-19, and none of which out-weigh the benefits of BNT162b2.
- The safety of the vaccine has only been assessed for a median follow-up period of about two months. Normally a Phase III trial will last for years, during which any safety concerns can be documented and investigated. That has not been possible in this accelerated vaccine development.
- A good example is the allergic reaction which was documented within a day after the UK began using the vaccine on its healthcare workers last week.
- Kids younger than 16 have only recently begun testing with this vaccine. This will include adolescents between 12–15 years of age.
- Additional risk groups such as young kids, pregnant women, and people with weakened immune systems have not yet been tested with this vaccine.
That said, this clinical study examined a large population of diverse volunteers, and the safety and efficacy was uniformly very good.
3. The vaccine…
The vaccine which has been approved by the U.K. and now by the U.S. is called rather clinically, BNT162b2. The “BNT” in the drug’s name presumably refers to the company, BioNTech, that developed the drug in record time in partnership with Pfizer. Read more about the company and people of BioNTech here.
BNT162b2 contains a messenger RNA (mRNA) which encodes the SARS-CoV-2 virus’s spike protein. SARS-CoV-2 is the virus causing COVID-19, and the spike protein is the knob-like protrusion surrounding the virus making it look like a crown or corona, thus its other name, coronavirus. The spike protein is the key which the virus uses to enter and infect our cells.
The mRNA vaccine only encodes a single protein, not the entire virus, so there is no possibility of an accidental infection from this vaccine. There are some fascinating viruses called retroviruses that are able to insert themselves into the host’s genome, and thousands of copies of both active and inactive virus are embedded in our DNA. HIV is a well-known example of a retrovirus. The SARS-CoV-2 virus is not a retrovirus. And since this vaccine does not encode an entire virus, there is no way for the mRNA to change our DNA, as some rumors falsely suggest.
Since viruses affect every living thing including humans, all cells carry aggressive enzymes and other means to detect and destroy foreign RNA. BNT162b2 gets around this by modifying the nucleosides, the letters of the genetic code in RNA and DNA, so our cells ignore the vaccine and don’t recognize it as an RNA.
The vaccine’s mRNA is encapsulated in a lipid nano-particle which protects the RNA from degradation, and allows the mRNA to get into our cells more easily.
Earlier this year, BNT162b2 passed a Phase I study (published here), which examined the vaccine’s safety and immunogenicity (ability of the drug to precisely activate the immune system against SARS-CoV-2).
The vaccine has now passed Phase II/III trials which are published in the New England Journal of Medicine, which you can read here.
4. The study…
Pfizer/BioNTech’s Phase I trial showed the preliminary safety of delivering two 30-microgram doses of BNT162b2 to healthy adult men and women in Germany and the U.S. Passing that first trial let the companies progress to this current more rigorous trial.
The phases of a drug clinical trial are explained on the FDA’s website here. The bite-sized summary of clinical trials is:
- Phase I — about a hundred healthy or sick volunteers who are studied for a few months to determine the safety and the appropriate dose of the drug
- Phase II — a couple hundred sick volunteers who are studied for months to a couple years to determine the effectiveness and side effects of the drug
- Phase III — thousands of sick volunteers who are studied for up to four years to determine the effectiveness and to learn about adverse reactions to the drug
The Phase II/III trials further tested the BNT162b2 vaccine’s safety (with many more people, and over longer time periods), and most importantly the vaccine’s efficacy. The latest trial used the same two 30-microgram doses, injected into the shoulder muscle, three-weeks apart. The BNT162b2 vaccine was compared to a placebo (just a saline solution with no active drugs).
A total of 43,448 people took part in the clinical trial and were injected with either the vaccine or the placebo. A web-based app randomly assigned each patient to receive either the drug or the placebo. Neither the patients nor the staff who administered the injections knew who got what injection — we say they were blind to the study. This overall study design is called a randomized, double-blind, placebo-controlled clinical study — the gold standard.
A placebo shows that the vaccine is indeed better than doing nothing. A good scientific clinical study always compares the drug to a placebo, called a control.
Blinding the study means there is no way for either the volunteers or the study staff to intentionally or unintentionally bias the study (such as putting healthier people in the vaccine group and putting sicker people in the placebo group, falsely making the vaccine look better than it is).
Randomizing is essential to make sure our two groups, the vaccine group and the placebo group, are as similar as possible. That we are comparing “apples to apples”.
And finally, a large sample size ensures that the results of the clinical study are real and not just from pure chance, from getting lucky and flipping heads five times in a row.
Patients electronically recorded any local or systemic “adverse events”, or if the patient needed to use medication to treat fever or pain within 7 days of each dose. This was the main safety data.
The natural yardstick for measuring the vaccine’s effectiveness is to simply count the number of COVID-19 cases in the study. Then compare the people given the vaccine to those given the placebo and determine which group had more cases of the disease.
People who ended up showing a standardized set of COVID-19 symptoms, or who were tested and confirmed by RT-PCR, were counted as cases. Another important metric was how severe the case was, especially since it is severe COVID-19 which is overwhelming the medical system thus exacerbating the fatalities associated with the disease.
5. The results…
Overall, there were 8 cases of COVID-19 in the BNT162b2 vaccine group, and 162 cases in the placebo group. There were over 18 thousand people in each group. These numbers lead to their calculated vaccine efficacy value of 95%. This percent measures how much the vaccine reduces of rate the disease compared to being unvaccinated.
One of the most important aspects of this study is the large number of participants, and their diversity. The age range spanned from 16 to over 75, equally split between male and female, and included white, black, Hispanic and other races, from three countries. Some of the groups had small numbers (e.g., those over age 75), yet despite this diversity, the vaccine’s efficacy remained consistent across the board.
This data, and more, is summarized in Table 3 of the paper published in NEJM as shown below:
The safety data shows that people with the vaccine had a higher incidence of pain at the injection site, fever, fatigue, headache, chills, muscle and joint pain, than those given the placebo. The total numbers of these incidences were low. The highest was pain at the injection site, reported by 298 people out of the over 18 thousand in the vaccine group, compared to 43 people in the similar-sized placebo group.
The complete summary of the safety data is shown in the figure below from the same paper:
Perhaps the most interesting and powerful visual of the effectiveness of the BNT162b2 vaccine is the detailed plot of COVID-19 cases as they accumulated in each group. If you count each case of the disease after the first dose of the vaccine or placebo, and graph them with the cumulative numbers piling up on the vertical axis, compared to the number of days after the first dose on the x-axis. You can see clearly that the placebo group rapidly gained COVID-19 cases, and that the vaccine group gained a detectable amount of protection as few as twelve days after the first injection.
6. Other comments…
I plan to take the Pfizer/BioNTech vaccine BNT162b2 after reviewing this data.
This is despite the current political climate and a president willing to falsely hype hydroxychloroquine and other dubious measures as a cure for COVID-19.
I am not part of a high-risk group, and I am willing to wait until front-line healthcare workers, older and sicker people, people of color, and other high-risk groups have had a chance to get vaccinated. I hope they all do indeed get vaccinated and quickly.
I have expressed reservations about another company, Moderna, especially about their top executive ranks and their profiteering and toadying behavior towards the current administration. Nonetheless, I know Moderna also has very good people in senior management and I am sure they have many dedicated and outstanding workers in the ranks. I currently do not have an opinion on their vaccine, but I do not feel comfortable with Moderna’s vaccines and others until I see similar data as what Pfizer and BioNTech has released publicly here.
Feel free to comment and give feedback — and especially important are any corrections to errors you spot.