Like every other vaccine that we’ve seen the clinical data on, this one also seems to completely prevent deaths from the coronavirus. I might be mistaken, but so far I don’t think we’ve seen a single SARS-Cov-2 fatality in the treatment group of any of the Phase III trials. As for severe disease, this one had a strong effect as well, but it might take a bit to kick in completely. 14 days after the single dose, there were 29 people hospitalized with coronavirus in the placebo group and only 2 in the treatment group, but if you look at the 28-day mark there were zero hospitalizations at all.
This makes one think that the full protective effect might be coming on a bit more slowly than the Pfizer/BioNTech and Moderna vaccines, but making cross-trial comparisons like that is risky. The coronavirus landscape has changed since the earlier vaccines, and you can see some of that in the way that the J&J data break out their South African trial. Overall vaccine efficacy was 72% in the US versus 58% in South Africa, where there’s been a lot more B.1.351 variant circulating. But they also have data from Brazil, where the P.2 variant there doesn’t seem to have made much of a difference, and the B.1.1.7 variant first noted in the UK doesn’t seem to be a problem, either.
What about protection against asymptomatic infection? Of the roughly 10,000 people in the treatment arm of the trial, 2892 of them were tested with or without symptoms for signs of coronavirus infection. The FDA’s take on the data (see numbered page 35 of this document) is that there is weak-to-no evidence of such protection out to day 29, and around 60 to 70% efficacy in the post day-29 data. Like the other trials, it seems very likely that all of this will also reduce transmission of the virus, although the study isn’t designed to track that specifically. We’re getting reports from Israel and the UK, though, that would seem to confirm this. I would be very surprised if the levels of efficacy we’ve been seeing didn’t have a strong effect on transmission, but you have to get the numbers to be sure, and I’m glad that those are starting to show up.
There’s a lengthy discussion of subgroups in the treatment groups (starting on numbered page 27 of this document), but what I get out of that is that there aren’t any huge differences. I’ve seen a couple of mentions this morning of lower efficacy against severe disease in >60 year old patients (see that document’s Table 16 on page 32), but the FDA document points out that this may be an artifact of only including cases that were confirmed at the trial’s central location by the time of the data cutoff. Looking at the overall numbers, the older patients look much more similar to the other cohorts, at around 75% VE against severe disease.
Now, about overall efficacy. It’s easy to look at the figures and say “Hey, that’s fine, but it’s not up to what Moderna and Pfizer/BioNTech showed”. That still might be true, but we don’t know what those latter two would have shown if they’d been run at the same time as the J&J trial. It’s also tempting to look at the J&J adenovirus vaccine and the Oxford/AZ adenovirus vaccine and decide that adenovirus vectors are a step behind the mRNA technology, but for the same reasons, we can’t be sure that’s right. Note that the Gamaleya Institute vaccine in Russia posted better numbers, for one thing. And the differences between the three adenovirus vector vaccines themselves are pretty significant: J&J’s data are for one shot of an Ad26 vector (a two-shot trial is still running), and their sequence has the stabilizing protein mutations in the Spike. Oxford/AZ is a different adenovirus (from the chimpanzee population), and their sequence is wild-type Spike without the stabilization. And then Gamaleya is a two-shot regiment, one with Ad5 and the other with Ad26, with the Spike mutations. (Both mRNA vaccines have the stabilizing mutations as well, for the record).
So while we can’t avoid trying to compare all these, we also have to realize that between the fundamental differences and the differences in the timing and locations of the trials, that our comparisons have a substantial chance of being off to some degree. What have we done in the past when we have had such comparisons to make? Good question! But we’ve never had a situation like this, where a whole list of different vaccines, many from completely different platforms, have been rolled out so quickly against the same evolving pathogen. So it’s not like there’s a standard playbook for all this. If we never see this sort of thing again, by the way, that’ll be just fine with me, considering what conditions cause it to happen.
So this vaccine looks certain to get Emergency Use Authorization in the US, and by the time we get on into April it should start making a difference in the vaccinated-population numbers. Production has been slower than J&J were estimating at first, although it now looks a bit better than their more pessimistic estimates. As detailed here, adenovirus vector production is yet another art form, and anything with a big cell culture step in the middle of it has the potential to act up (and for reasons that can be quite difficult to figure out).
But the big message is the same: right now, variants and all, we’re winning. The vaccines work, there is a whole list of them, and their production is increasing while we watch. The countries that have gotten off to faster starts vaccinating their populations are already seeing the effects, and no bad safety signals are yet complicating things. Nor are we seeing evidence so far of antibody-dependent enhancement (worse infections recurring in people who have already been vaccinated). If we can keep this pressure up and keep ramping up vaccine supplies and their rollout around the world, we are going to beat this virus. Good riddance to it.
