Pfizer and BioNTech Conclude Phase 3 Study of Covid-19 Vaccine Candidate
investors.biontech.de
investors.biontech.de
Do those vaccines work on all mutations or are they like the common flu vaccines that must be adapted every year?
Oddly enough, the G614 mutation is moderately more vulnerable to neutralization.
Once enough people are no longer susceptible/vaccinated, there may be considerably more selective pressure for the virus to mutate in ways that antibodies to past variants don't work. Whether we'll get variants that are virulent and bypass immunity is TBD. The spike protein is functional; changes to it that bypass immunity likely reduce function.
As an example of why, the comment you are responding to mentioned the spike being functional (it is used by the virus for cell entry) and it is also targeted by our antibodies. So, for the virus to evade antibodies, it would have to change the spike enough so that antibodies don't detect it anymore. But, by changing it would likely lose some of its current efficacy.
I think consensus is we don't know for sure, but there's reason to be hopeful. SARS-CoV-2 probably won't evolve as fast as the flu, which undergoes a "sexual-like" evolution process called "re-assortment." On the other hand, CoV-2 has "re-combination," which gives similar results, and it does have zoonotic hosts.
Note there is some correlation between virulence and severity. For something with a longer incubation time, increased viral load tends to mean both increased virulence and transmissibility. This relationship is far from universal, though.
Why? Has it had a ton of time to evolve?
https://www.medrxiv.org/content/10.1101/2020.07.22.20159905v...
They just finished the first study on the regular virus yesterday!
To quote his summary:
> Bottom line: the coronavirus can’t undergo the wholesale changes that we see with the influenza viruses. And the mutations we’re seeing so far appear to still be under the umbrella of the antibody protection we’ll be raising with vaccination, which argues that it’s difficult to escape it.
He said something like that most of the work in testing is for the "carrier" or something like that(in Spanish). Once your vaccine works with that you could modify the vaccine very fast with little consequences.
Hew also told me that you can share "carriers" for different illnesses and he had tried to convince politicians for decades trying to create "generic carriers" in order to be prepared for something like this.
But when you can change payloads of a pre-validated generic carrier at will you are roughly on the same level of biotechnological advancedness as the mRNA companies anyways, both are lightyears ahead of ancient techniques like breeding weaker viruses in animals or neutering them somehow before injection. A lot of vaccine skepticism seems to be based on the performance of those old ways, it would probably be quite wise to avoid a vaccine that was come up by old trial&error methods in less than a decade.
~20,567 in each arm
162/20,567 cases in the placebo arm (~0.79%)
8/20,567 cases in the vaccine arm (~0.04%)
Absolute risk reduction of ~0.75% (over the time period of the study, which is difficult to tell).
Number-needed-to-Treat (NNT): 134 vaccinations to prevent 1 symptomatic case over the study duration.
Keep in mind, this is over some time period. Annualized, these numbers would almost certainly increase. We don’t know how many days/weeks/months it took to reach 162 / 8 cases respectively (something between ~5-6 months and ~5 days)
It's a hard problem, and even though the clock is ticking, we also need to get it right the first time.
Things we still don't know:
- Does the vaccine also stop you from contracting the virus asymptomatically and spreading it? People enrolled in the trial were only told to get tested if they showed symptoms.
- How long does the immunity from the vaccine last? We won't know this for some time.
"The Phase 3 clinical trial of BNT162b2 began on July 27 and has enrolled 43,661 participants to date, 41,135 of whom have received a second dose of the vaccine candidate as of November 13, 2020."
So there is no single date one can reasonably use 41,135 or ~20,567 for the efficacy calculations. As the observations continue (expected up to 2 years) there could be much more useful data there.
I also guess the people who haven't received both doses but got sick before are separately counted.
The only useful numbers at the moment we have are 8 and 162 (and 1 and 9 for the severe cases). And that we can assume that from all thousands vaccinated these 170 in total got sick by chance, and that the thousands were carefully enough selected to represent bigger population, and using that we can expect that the efficacy won't too dramatically change as more data come in, the same way as the polls can use smaller samples to conclude something about bigger population, if the sampling is careful enough. But some changes are expected.
It appears it's still too early to know if those who are vaccinated could protect those who aren't, or if the vaccine protects only those who received it (1) -- but anyway we know that still not all of those who will be vaccinated will be protected from having a severe case: there was up to now one severe case in the vaccinated group, versus 9 severe cases in the placebo group, 11%.
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1) https://www.medscape.com/viewarticle/941030
"In an ideal world, a vaccine would prevent infection entirely and, it follows, also prevent disease and severe disease. But this may be hard to achieve for a respiratory virus vaccine. Animal challenge data suggest that vaccinated animals may still be infected even if they don't experience symptoms. A vaccine that is able to reduce the severity of disease, even if it cannot prevent infection entirely, would obviously still have enormous public health value. Therefore, this is what trials target as their primary aim."
Keep in mind the definition of a case here is having symptoms, so we don’t know if the vaccine prevents lightly symptomatic or asymptomatic cases, which may or may not result in transmission.
Its current prevalence is irrelevant because if we live how we want to live it will be everywhere (assuming no vaccine).
Over the course of a longer period of time and with cases on the rise as they are now, I'd expect the risk reduction to be much higher.
Edit: Also, these numbers are somewhat skewed by the fact that not all 40k people got the vaccine/placebo at once, but over a period of time.
That’s not good though... really could but a kink in establishing herd immunity until everyone is actually vaccinated.
b) It's likely that it is protecting against those. But hard to specifically prove that it's protecting against each and every symptom. I think the hope is that if you don't develop lung issues, you are unlikely to develop long term damage.
Maybe I'm misunderstanding the data here. It seems like we've only directly proven that the vaccine has been effective at reducing the normal symptoms (coughs, fevers) to the point where candidates don't seem to be prompted enough to go get tested anymore. It doesn't directly prove those candidates didn't get covid.
Still, I'll use this vaccine if I can't get Moderna in time. The safety profile looks great.
What does that mean? Don't both vaccines work exactly the same? Both are mRNA vaccines.
I can't say anything about these vaccines, but there is such a thing as a non-sterilizing immunity, that would prevent you from developing COVID-19 but still be infected and able to spread SARS-CoV-2.
What does this mean?
As I understand it, all vaccines ever do is provide you with a prepared immune system for when you do get infected.
But presumably incidence is low because of safety restrictions (lockdowns, masks etc.) which are untenable long-term. Whereas if we can vaccinate O(everyone), we can, maybe, stop the restrictions?
https://news.ycombinator.com/item?id=25111284
In short, we still don't know which measures would have to be kept even when a lot of people are vaccinated. It will be much better known in some time, but it's still not known at this moment. It depends on sterile immunizing properties of the vaccine, which are still unknown.
Edit: re the Moderna protocol mentioned in sanxiyn's comment below: even if they will measure sterilizing immunity (as one of their "Secondary" objectives), as far as I know, they still haven't published something on that topic (1) From them we still have only data on the level comparable to those from Pfizer/BioNTech:
90 cases in placebo, 5 in vaccinated, 11 severe cases, all in placebo group. Where "cases" could simply be defined "those who were recognized of having Covid-19" (as the illness). (Also see my other comment here for more general references about the primary objectives of all Phase 3 trials).
Here's what Moderna only writes about their secondary objectives in the only release: "Key secondary endpoints include prevention of severe COVID-19 disease and prevention of infection by SARS-CoV-2. The trial will continue to accrue additional data relevant to safety and efficacy even after an EUA is submitted." Meaning, eventually, we should be able to know more.
I didn't know that Pfizer doesn't even have that kind analysis written in their protocol, thanks. I'd hope they can add that in some later phase.
1) https://investors.modernatx.com/news-releases/news-release-d...
https://www.modernatx.com/sites/default/files/mRNA-1273-P301...
But preventing 0.75% of the population from getting it out of the 0.79% who got it implies 94.9% (0.0075/0.0079) of those who _would_ have gotten it were prevented from getting it. That's the relative ratio.
I agree with the poster that the relative number seems more interesting. There are lots of things going on right now (masks, social distancing, etc.) to prevent people from getting COVID. The fact that only 0.79% of the placebo group got it implies a lot about _other_ mitigation factors, and puts a limiting force on how many can be saved by the vaccine (a number less than or equal to 0.79%). Like OP, I wonder if there's any case where the -0.75% number is interesting in and of itself. In fact, if we weren't social distancing, presumably the prevalence of COVID would be much higher and thus the absolute ratio of people prevented from getting COVID would be higher too.
The 95% effectiveness number should (theoretically) be the same no matter what other measures you're taking. It would reduce 0.79% of population from getting it to 0.04% getting it, and would reduce 10% of the population from getting it to 0.5% of the population getting it. I'm totally ignoring that lots of people getting the vaccine will lead to less people getting sick and less people spreading it (herd immunity), but you get the point.
(No actual math done here, I'm ballparking it based on looking at error ranges with sample size 100 at work; my main point is that I don't think the ~20k enrolled in each group affects this particular error range, so even though "94.9%" is stated precisely the actual data isn't nearly so precise)
I hope this doesn't come across as snarky, but this seems like it could have a larger impact in the US than elsewhere, since we've (collectively) been doing such an abysmal job of doing masks + distancing.
Intuitively, I would expect the confidence to be pretty low - after all, if tomorrow 2 more people in the vaccine group happen to get sick, the relative risk reduction will go from 20x to 15x.
Is there anything wrong with this reasoning?
That said, if we assume that there are in total 170 cases (which is true at this point in time but will change), and that there are 162 cases in the control group and 8 cases in the vaccine group, we can construct a posterior of the VE. Here's an older posterior (done with data from the press releases in the first IA a few days ago) http://blog.fellstat.com/?p=468 that graphs this posterior. There is some uncertainty, but as you can see results are still promising. That said we just don't know how case counts will change, and while it will be fascinating to watch the results change over time, these sorts of tests are just about getting enough data to mark a vaccine as effective, not about trying to extrapolate any larger effect.
Additionally, if the virus has an R greater than 1, preventing one person from being infected has a larger impact on total infected population.
Thus, even if it does not completely prevent spread, if just a part, or even a smallish part, is prevented, that also helps others.
(Same thing in mask discussion. Lots of people dismiss masks because they may not completely prevent an infection; that is stupid, because masks still decrease the probability of infection (and more importantly, spreading to others).
Once the vaccine rolls out, people will return to previous habits and without the vaccine a large percentage of the population would be infected, so these numbers look completely different (i.e. absolute risk reduction of at least 45% from 50% to 0-5%, and NNT of something like 3-to-1 to 10-to-1).
SCNR
It's about eliminating excessive fear. And fear kills economic activity.
“If our potential vaccine receives an EUA, we would propose amending the study protocol to create a process so that interested, eligible participants who received the placebo could ‘cross-over’ to the vaccine arm of the study,”
i don't see how that rate implies anything about the severity of the infection
In a worse world it could have been the case that e.g. the vaccine was 90% effective at preventing infections but still had the same number of severe infections because it did nothing to help the most vulnerable patients.
You're probably reading U.S. media sources.
Wouldn't surprise me at all if BionTech have similar partnerships with large pharma companies in other countries, where the media there similarly claim it for their national champion.
> BionTech created it and Pfizer is handling logistics, approval, and distribution
AIUI, Pfizer is also handling US and some EU manufacturing.
I work on a medical consumer device. Would be madness to market this ourself. A big company has the resources for distribution and marketing.
https://www.statnews.com/2020/11/17/pfizer-may-be-within-day...
Also remember that by vaccinating the highest risk patients first we can make big impacts in the death toll without necessarily stopping the spread of cases.
If society continues to coddle anti-vaxers, it reinforces a positive incentive for selfish behavior, which in turn creates a negative drag on overall well-being. At a certain point, society shouldn't allow the selfish acts of small group of individuals undermine the well-being of society at large.
Obviously, there would need to be ample warning and a concerted effort to educate everyone on consequences. Once these requirements are met in this hypothetical, I believe the moral thing to do is to stop wearing masks and stop social distancing.
That said, this is an idealized hypothetical. In reality, there will be many people who can't get vaccinated for reasons that are not selfish. In this case, there is still a moral dilemma, but I'm unsure on how I'd approach it. Surely, asking 200 million people to wear masks for another year to save 1 life isn't worth it. The question is where to draw the line.
EDIT: I am getting serious downvotes for this comment! Whoops! I do not mean to suggest people should not take the vaccine, only that the optics of news presses look bad. I say this as someone who takes the Flu vaccine every year and elected for the HPV vaccine a few years ago
For much the same reasons as you don't want people adding additional baseless speculation to passing observations of you that you may be a pedophile in passing conversation.
You could have gotten your point across better without insinuating negative intent, i.e. "As someone unfamiliar with the reporting process, can someone more familiar with the process explain how Pfizer's effectiveness number went from 90% just recently to 95% today? Thanks in advance."
This comes across much differently than "this seems like these numbers -- which I confess I do not understand -- seem manufactured by the drug companies to look good."
Not a crime, but strictly speaking, thats how theories are formed. You test them or otherwise find evidence that contradicts them.
I think, "originally" is not the right term. "Pfizer’s Early Data Shows Vaccine Is More Than 90% Effective".
Now more data is in, and it is indeed more than 90% effective, more like 95%.
They already have sold the vaccine, and it won't be sold over the counter. I don't see any gain in telling to have 93%, 95% or 98% efficacy, if you don't have it.
From this comment, which summarized the statistics of the phase 3 trial: https://news.ycombinator.com/item?id=25136588
- The percentage of people in control that had confirmed COVID-19 cases was ~0.79%
- The percentage of people in treatment that had confirmed COVID-19 cases was ~0.04%
- This represents a risk ratio of 0.04/0.79 = ~0.05.
A risk ratio of 1.0 means that there was no reduction in risk, i.e. the treatment had no effect. A risk ratio less than 1.0 means that the treatment reduced the risk (or was correlated with this), and above 1.0 means that the treatment increased the risk (or was correlated with this).
Since the risk ratio of treatment was 0.05, there was a 0.95 reduction in risk, which is where the 95% number comes from.
The 90% efficacy is reported based on the second readout data, which was all the data they had at the time. The 95% efficacy is reported based on the final readout data, which was only more recently available.
Note that the media has not done a great job of indicating that the initial Pfizer (and Moderna, for that matter) results were based on interim analysis.
I am surprised so many people are suddenly in full "believe the science" mode, especially when big pharma companies weren't exactly the most ethical players on the market in the past.
Sure, we should be skeptical of the government line on the pandemic, but why should we be skeptical of a product that comes from a company whose product must work for them to make money?
I think instead of letting our previous biases in one arena influence our current decision making in another, we should look at the evidence, make an independent decision, and then loop back on that when the evidence changes. Government bad != private company creates product that doesn't work
And what's with the trust in the market to fix things? The 737-MAX crashes did not affect Boeing share price or Boeing management in any meaningful way, neither are safety problems with the new covid vaccines going to affect Pfizer or Moderna.
> I am surprised so many people are suddenly in full "believe the science" mode
Two reasons:
1. We want our lives back. Covid sucks and people are getting tired of the precautions. Many of us are still being careful to protect others, but "covid fatigue" is very real. A vaccine promises tangible light at the end of this tunnel.
2. While many of the efficacy trials are shorter than normal, there's no reason to believe that these vaccines are dangerous. mRNA ones, in particular, basically can't give patients the virus itself, unlike many other kinds of vaccines.
Yes, the vaccines may be riskier than we're accustomed to. GBS is a 1 per million side effect in most vaccines, with some proportion of these people having permanent side effects. I wouldn't be surprised if we find that these vaccines are more like 1 in 25k. But that's better than the odds even young people face from COVID-19.
Thinking about it from a societal perspective, I'm willing to take a small risk from getting the vaccine to avoid inadvertently getting and spreading the virus to more vulnerable people like my grandparents.
From an overall risk/reward perspective, I would include the risk of subsequently infecting your parents, grandparents or other vulnerable/high-risk family/friends with severe disease as a 'potential long term side effect' of covid in a young/low-risk individual.
(1) My company switched to work from home two or three years ago, I've just recently subscribed to Walmart+ so I've got free grocery delivery for a year, I've gotten into the habit of making my own meals which is healthier and cheaper than how I ate pre-COVID so I'm going to stick with that even after COVID is gone, and my socializing was almost all online before COVID.
It is no problem for me to keep mostly quarantined for another year.
(2) The few times in the next year I will have to interact closely with other people will probably be with people who have taken it (e.g., doctors and dentists).
(3) While it is true that mRNA vaccines cannot give you the thing they are vaccinating against, it is still possible they will have other side effects. As far as I know there is no way to determine the long term risk of a medicine other than just waiting to see.
(4) I live in a county that has not been hit hard.
(5) It looks like there are at least two vaccines that are going to get quick approval, and I believe there are more deeply into their phase 3 tests.
Putting this all together, it seems I personally have a pretty low chance of getting COVID, and if I do get it a pretty low chance of spreading it while I'm still asymptotic, so can afford to wait and see if any of the vaccines have longer term issues or if one of them is clearly better than the others.
I'll be the first in the queue personally. Lets get back outside, even I'm bored of these walls now.
Excellent! That is exactly what I want. The more people who take it because they are either at high risk, or because avoiding exposure seriously harms their lifestyle, the more data there will be for me when I decide to take it.
As far as side effects go, the kind of things that take years to show up are usually things that you'd only see in a medicine that you have to take regularly.
The latest research suggests that we probably get long term COVID immunity. Those few cases of people getting it twice were probably people who got a small viral load the first time and didn't develop strong immunity.
All the COVID vaccines look like they will be take once (or take twice over a short period) and that's it, so we almost certainly won't see anything like people developing cancer from it 5 years later. Those things take times to build up, like say we had with Actos and bladder cancer, with each time you take it adding to the risk.
If there are long term bad effects from the COVID vaccines, the underlying damage will happen within a couple weeks or so of taking them, and then should start being detectable in the health statistics of people who took it versus people who did not within a year.
Thus, at the latest we should know about any long term effects by the time my Walmart+ subscription is up for renewal, which is perfect timing.
Good points regarding the build up, thanks for the response
I just trust the scientific process. Yes, the conclusions currently drawn from the evidence can be wrong. I'm not disappointed if it is. If scientists gain new insights, it just means the proces is working.
That said, I believe the legal repercussions of lying about these studies will be too high to stomach, so I do trust the companies to be truthful here. That doesn't mean that it is irrational to choose not to trust them.
Again though, the fact that it is inevitable that we will eventually find out is why I personally believe the data today - I trust the company to not sacrifice long-term credibility for short-term gains.
Also science can be corruptible as well. It was once scientific fact that non-whites were inferior to whites. The "father of gynecology" experimented on black women because it was scientific knowledge that black women don't feel pain.
https://www.independent.co.uk/news/world/americas/james-mari...
It was once "science" to cure sick people with leeches. It was once science to give "misbehaving" women hysterectomies or lobotomies. One of the most famous ones being rosemary kennedy.
> If scientists gain new insights, it just means the proces is working.
I guess the victims of mengele and U-731 appreciate your confidence in the "process".
For someone so critical of religion, you have an almost blind and zealous and unquestioning faith in the "scientific process".
When money, corporations and politics are involved, you should be skeptical. Even if it is "science". And pfizer and these companies aren't in the business of science, they are in the business of making money.
"Trusting something" !== "An almost blind and zealous and unquestioning faith"
Trusting the scientific process doesn't mean you shouldn't be skeptical. It means the opposite. If a company lies, we will find out eventually. You can look at the evidence. There will be independent data eventually. You don't need "faith".
Why you needed to involve Mengele to make an argument is beyond me. Invoking Godwin's law will never help you win a discussion.
If we're wrong we can be disappointed about it later