What Should Investors Know About AstraZeneca's Coronavirus Vaccine?

In this video from Motley Fool Live recorded on Nov. 23, Corinne Cardina, chief of Motley Fool's healthcare and cannabis bureau, and Brian Orelli, Fool.com contributor, discuss how AstraZeneca's (AZN -0.25%) coronavirus vaccine, AZD1222, works. They also talk about the recently released data showing that using a lower dose for the first vaccination seems to result in better protection than starting with the full dose. Finally, there's also a discussion about what investors should expect next from the company.

Corinne Cardina: The company is in partnership with the University of Oxford, and they have a vaccine candidate and they just released interim analysis, their Phase III clinical trials, and it showed that their vaccine candidate has an average efficacy of 70% in protecting against the coronavirus. We'll talk more about the specifics of this 70% number in a moment, but I'd like to talk about how this vaccine works, just to set the stage. It takes the mechanism of a non-replicating viral vector using DNA sequence for the coronavirus spike protein delivered via chimpanzee viral vector. Brian, can you explain how this vaccine works? Is this a traditional approach compared to the novel mRNA candidates from Pfizer (PFE -0.12%) and Moderna (MRNA -1.39%)? Can you explain this for us laymen?

Brian Orelli: Yeah. It's definitely not traditional. Traditional would be sticking a coronavirus that we've made so it doesn't replicate as a vaccine, or purifying a protein out of the coronavirus and then sticking that in. This is using, as you said, a viral vector. It's using another virus to inject the DNA into the patient cells. Then the patient cells use that DNA just like they use their own DNA, and make a protein, in this case, a protein for the coronavirus. So instead of just sticking the protein directly in, you stick DNA that then makes the protein within the cell. The main reason why you would do this is because it's faster. Once you know the sequence of the protein that you want to stick in, it's relatively simple to design. The viral vectors are all the same. You use the same viral vector, you're just sticking in different DNA that you want to express. Then you express that, the coronavirus protein.

Cardina: Excellent. This vaccine candidate was assessed over two dosing regimens. It turns out that one dosing regimen was 90% effective. This was actually one where the first dose, this is a two-dose vaccine, the first dose is a half dose. Then you wait a month, get a full dose. The other one showed 62% efficacy. When the participant received the full dose, waited a month, got a second dose. The exciting news here is that if you need less of the vaccine dose, they can distribute more of the vaccine. That is good news. Brian, when the larger data set is available, this was sent out in a press release this morning, what are you going to be looking for in the larger dataset?

Orelli: I'd really like to see the breakdown of how you get 90% or 62% is you look at the number of patients that got the vaccine and then got COVID-19 versus the placebo group that got COVID-19. Obviously, there's going to be more people in the placebo group than in the vaccine group. But what are the raw numbers there in terms of the breakdown? The 90% group, I think was only about a quarter of the total population of vaccinated people. We're talking about pretty small numbers and so I'm a little worried that 90% could be erroneous based on the fact that just if one more person in the vaccine group got coronavirus, maybe it drops down to 80 or 70%. Then we're talking about that much difference. It's a little surprising that the smaller dose would give you a better efficacy. I heard one of the executives from AstraZeneca this morning, talked about how he thought that the working hypothesis is that maybe the smaller dose primes the immune system better. Then you get a better reaction till the second dose than if you gave a full dose the first time. But I think we need more data to really know whether that 90% is really accurate.

Cardina: Absolutely. What is going to be next for AstraZeneca? Are they ready to file for an emergency user authorization from the FDA?

Orelli: Yeah. None of this data is actually from the US trial. It's from Brazil and the UK and maybe some other places, but sounds like they're going to use that data to file the EU. They also need safety data and there didn't seem to be any safety data that I saw in the press release and I don't know how close they are to having that data. You need, I think, 60 days of safety data on half of the population of the clinical trial before the FDA would even look at your emergency use authorization.

Cardina: Yeah, great context there. I have a question about the endpoint. The endpoint is the goal of what is being tested in the trial. The primary endpoint for AstraZeneca's trial is preventing COVID-19 disease, so my question is, is there a difference that investors and everyone needs to be aware of between preventing COVID-19 disease and preventing asymptomatic transmission? In theory, could you get vaccinated, get infected with COVID-19, never get sick, and still spread it? These vaccines don't protect you from becoming infected; is that right?

Brian Orelli: I don't think we really know the answer to that question. I think it's likely that your antibodies are going to bind it up pretty quickly and so you're probably not going to be spreading it whether you want to measure actual disease or just testing positive, but being asymptomatic. I think the Pfizer endpoint require that somebody had at least one symptom, I think, of COVID-19. You had to test positive, but you also had to have at least one symptom, so they are testing the disease too.