Hi everyone. I'm sharing our most recent 16 minutes episode here because it covers vaccines a topic that we've covered here since January of last year in our early and ongoing pandemic coverage as part of our mission to continue bringing you everything you need to know about this crisis and how Tech and in this case bio changes our future you can find our past coverage at a six and z.com coronavirus and a six and c.com vaccines, but in the discussion that follows the team digs into vaccine efficacy.
Agassi and Frameworks given the third emergency use authorization approved vaccine more details in the intro that follows. Welcome to this week's episode of our news analysis shows 16 minutes, um, zorin and our topic today is the ongoing buzz and the mixed news around the Johnson and Johnson vaccine, which was the third vaccine for covid Approved under emergency use authorization by the FDA just a few weeks ago. And which Johnson & Johnson reported in its press release as the first single shot vaccine and as having 85%
The in preventing severe disease across regions studied meanwhile stat headlines reported 66% efficacy overall and 72 percent in the u.s. In preventing moderate to severe disease with their headlines saying it is quote a weapon, but not a knockout punch and then we have various experts saying everything from quote disappointing to pointing out the dangers of comparing this vaccine to other vaccines such as Pfizer's and modern has both of which we've talked about on this show. You can find all our ongoing vaccines coverage at a 16 z.com.
Vaccines but in this episode since 16 minutes is about teasing apart. What type and what's real in the news and where we are in the long Arc of innovation. We asked the a 16z bio team for their Frameworks General partner Jorge Conde joins us. He's been in all of our vaccine episodes in he also previously LED strategy and product for pharmaceuticals company along with bio editorial partner Lauren Richardson who was previously an editor at plos biology and hosts our sister show Journal Club on Bayou eats world. She also holds a PhD in Pharmacology, so
Question is very much in the headlines. Let's tease apart. What type in what's real about J&J slower efficacy rates do the clinical trial endpoints account for those or is there something else we should be thinking about here about why the results are
different the J&J trials were being conducted when the virus was more widely spread when arguably there were more variants circulating through the population and some of the early evidence suggests that these vaccines have different rates of efficacy against different variants of the source code be to virus when the
Vaccines were designed they were designed around one dominant variant and that dominant variant was circulating much more widely earlier on Independent MC. Whereas new variants emerged new variants become an increasingly larger percent of the virus population. So if any given vaccine has differential efficacy against different variants and the mix of those variants in the population changes over time, that could have an impact on the
Leva can see that you see in terms of the vaccines performance.
Yeah, the variance and the distribution of variance is also linked to the populations that these vaccines were tested in the moderna vaccine was tested only in the United States. The Pfizer Beyond Tech was a worldwide study a hundred fifty two sites worldwide, but still dominantly test in the United States, whereas the Johnson and Johnson vaccine was tested 40% in the United States 40% in Latin America and 15%
Sent in South Africa and there is this critical variant that was first observed in South Africa. So the Johnson and Johnson vaccine was being tested against these other variants and you're also dealing with things like differences in host immune systems from these different populations. One thing that's really important to think about when you're comparing the Moderne and Pfizer vaccines to the Johnson Johnson vaccine is that it is very difficult to directly compare their efficacy because the
These were set up to have a different end point and when you're designing a clinical trial the endpoint is how you decide. What success is Moderne Pfizer were looking at could they prevent any symptomatic covid infections after two doses Johnson & Johnson is looking at whether it could prevent moderate to severe covid after one dose. So that difference you can almost think about it as like they actually set themselves a higher bar.
Let's talk some more about what these studies are targeting because that has a big effect on the stats which have received so much attention. What was the Benchmark these drug companies were going for and how does that Target potentially affect how we should look at these
numbers when the US government set out the Benchmark for what they were looking for in an effective covid vaccine. They were targeting two things. Number one. They were targeting preventing symptomatic illness and the hurdle rate that they had set was a 50% reduction in the prevention of symptomatic illness now.
We should take that phrase symptomatic illness and tease it apart because that is not the same thing as severe illness. That's not the same thing as hospitalization and that of course is not the same thing as death. And the reason in part why symptomatic illness was set as The Benchmark was really for Speed to one of the things that you can easily measure is someone symptomatic or not. And that is likely going to happen at a higher rate than someone getting hospitalized and unfortunately at a higher rate than someone dying from
the covid disease and so that became sort of The Benchmark to hit is symptomatic illness that you could make the argument that there's another Benchmark that you could have set this out which is infection, right? You know what number of people were infected what percentage of cases is infection prevented in a vaccinated group versus an unvaccinated group and the argument against doing that was that of course, you'd have to go out and test everyone and figure out who was infected and who wasn't and that in of itself could have been another limiting factor into getting you know data back.
Quickly so we can make an assessment as to the quality of these vaccines.
Okay. So given what you're both saying this Need for Speed and that this is not an Apples to Apples comparison. How should we look at the JJ numbers in the context of the other EU ASR emergency use authorization like help me tease it apart since it's still kind of hard to evaluate giving all the mixed news and Buzz out
there by that measure a 50% reduction in symptomatic illness all of the vaccines that have received emergency use authorization. Thus far have far exceeded that Benchmark. So Jay and Jay was in the low to mid 70s.
Moderna and visor were much higher. They were in the mid-90s. So they all far exceeded the original sort of threshold Benchmark that was set up for emergency use authorization.
There's been a lot of talk about what we have this hundred percent protection against death and hospitalization and all three of the vaccines are a hundred percent against death and hospitalization. Some of those statistics have been revised slightly downward as more data has come in. So what does all this mean and what can people take from this as they kind of think? Well, hey, I want the 95% one in that 72 percent. It's natural for people.
Ain't that right? So in any typical year of flu vaccine probably are anywhere between 40 to 60 percent effective. So the fact that we're in the 70s and 80s and 90s. We've already cleared a very high bar and mind you we did all of that within one year. So that in of itself is a remarkable thing. So I'd say a couple of things when it comes to that I would take the first vaccine that's offered to me. If a point in time comes when all three vaccines are available in all three vaccines are an option and you can pick and
Choose between and among them then the question becomes. What is it that you're optimizing for? If the main concern is trying to ensure that you don't suffer from severe disease or risk death from the data we have today all three vaccines while not perfect seem to be effective. If your concern is around preventing symptomatic disease, you're absolutely right that the data we have today suggests that the Pfizer and moderna vaccines are more.
Deaf, even though we don't have an exact apples-to-apples comparison. They seem to be more effective based on the limited data. We have at preventing symptomatic disease that said they also seem to have slightly more Adverse Events associated with them. When I say Adverse Events, it's fatigue or feeling crummy or pain Etc. And then convenience is an important factor as well. So, you know getting one shot versus needing to schedule two shots in a follow-up and making sure you go back.
Back at the right time within the right window and that you're compliant in that regard is another important consideration. So when people have the choice to choose specific vaccine, there are going to be many factors that go into that decision. Not just the headline number that we've been discussing right
now. What else do we need to know here to make sense of these headlines about the efficacy of J&J or any vaccines efficacy during an outbreak or a pandemic like what are we not hearing enough about it's important not to think of a clinical trial as the end.
A clinical trial is really just the beginning especially as covid is continuing to mutate as it moves through populations and possibly becomes endemic you meaning that we have covid-19 and versions of it constantly circulating in our populations. So this is the preliminary answers we have to how effective these vaccines are. They are not the final answer. What's the significance of the je vaccine in terms of the way it's stored and the fact that it's one shot instead of to
the change a vaccine is a
Dna-based vaccine DNA is double-stranded. It is sort of much more robust than mRNA which is single stranded and so you can store it in a much less restrictive environment in terms of temperature and moderna and Pfizer vaccines have to be stored at such extraordinarily low temperatures. At least. That's what the initial data was. That means that only the most sort of advanced refrigerator technology can be used which means it's limited to certain centers which means it becomes much less accessible. And so the fact that the je vaccine
A single dose means more people will be protected for a given Supply and the fact that it can be stored with standard Cold Storage techniques means it can be much more broadly distributed which means it'll be more broadly accessible. And by the way, it's also much less expensive changes providing this at cost and so on the cost per dose is also lower
yet. Despite all this. I think there's still a point of view out there that says look the sounds like hype to me. I keep hearing they're the same but I sort of like the higher efficacy rate. Thank you very much. So why is this Viewpoint persisting if indeed they're all really good vaccine.
Scenes, let's separate the hype from the real there
and fortunately in terms of the height folks have felt compelled because of the public health interest in making sure that everyone is vaccinated to just say that all three vaccines are the same and they're not the same but they are all effective certainly by any standard that we set for ourselves when starting the process to find a covid vaccine in the first place and I think that both for individuals and certainly for society more broadly. I think that is what could have the most beneficial
You're saying good for society and just kind of General sense of getting folks vaccinated in reaching some sense of herd immunity that
are active virus is circulating broadly the greatest risk you have is being infected by the virus. And so the best protection you can half of that is being broadly protected as opposed to trying to wait for the quote unquote best one.
Okay. So let's get to the big picture here. What is this a for not just the next few weeks as vaccines continue to reach more Americans, but even for the future of how we think about vaccinations for covid in the longer term
the
Reality is tsarskoe V2 is not going away. It's going to be with us. Probably going to be endemic like influenza like the flu and we're already seeing efforts by the vaccine producers like moderna that have announced that they are already developing an updated version of the vaccine for new emerging dangerous variance. And so you will get boosters. There will be others that are made available over time and that's why expediency and time.
So important here because this isn't the last effects in you're going to take it's really just the beginning of protecting yourself and the population.
Okay, we've gone through the news that we've teased apart what's happened? What's real? We've looked at the data now, let's get to the bottom line.
I think the takeaway for me is that in the midst of a raging Global pandemic scientists government's industry came together to produce these extraordinary vaccines at incredible unprecedented
speed.
We are just really beginning to understand how these vaccines work how they work in the real world how they work with diverse populations and against different variants or hey Lauren. Thank you so much for being with us today. My pleasure. Thank you.
