First, as many have been mentioning, it’s tempting but quite difficult to compare the vaccines (and vaccine candidates) head-to-head by looking at their phase III data. I would only feel safe doing this when large differences show up (like 60% efficacy versus >90% efficacy), and only then after a good hard look at the trial populations, the possible variant forms of the virus therein, and so on. We have to remember that this pandemic is not a set of trials versus relatively static targets like atherosclerosis or small-cell lung cancer. The SARS-Cov-2 virus has only recently jumped into the human population. Like most any virus, it is throwing off mutations all the time, but viruses that have been in the human population for much longer have often settled into some broad energy minima by now. The current coronavirus hasn’t had a chance to do that yet.
So the variants we’re seeing can indeed change the face of the pandemic (look at how the B.1.1.7 one took off in the UK, or B.1.351 did in South Africa). Not all of these are going to make a difference to the vaccines or to their trial data, but some of them (like B.1.351) certainly can. All this is to say that if we ran another Phase III with the Pfizer/BioNTech or Moderna vaccines in the same populations that (for example) J&J and Novavax have been seeing recently, that their numbers could be different than they were in their original trials and more similar to the latter ones. I’m still reserving judgement on the Oxford/AZ vaccine – those trials were run earlier, but the data on them is (famously) piecemeal and from some directions not very impressive.
That’s one point. A second one to remember is that all of these trials are designed to read out when they hit a certain number of cases, and their timing is thus dependent on how many people are getting infected. If the coronavirus is ripping through a given population, that’s very bad for them – but actually speeds up such a trial if that’s where it’s taking place.
Consider, then, the current cases of Novavax and J&J, both of whom still have ongoing US trials (the latter is for a two-dose schedule, as opposed to the one-dose trial that has completed). One of the very interesting things that’s been happening so far this year is a steep drop in coronavirus cases in almost every region of the US. I really don’t think anyone saw this coming (I didn’t), but it looks like there was a peak in the first week of January. Many other countries have seen something similar, and there’s been a lot of speculation about what’s going on. I won’t add any of my own, except to say that I’d bet that it’s not any one single factor, but several adding up simultaneously. (It’s also worth noting that in the last week or so this drop seems to have slowed, so now everyone gets to wonder if things are going to start going up again!)
At any rate, this has all surely slowed the pace of these clinical trials. I thought about this while reading some comments made by Novavax’s CEO Stanley Erck, as reported by Anjalee Khemlani. They have apparently been involved in talks with the FDA about getting their vaccine approved on the basis of their UK/South Africa data, without waiting for the US trial to conclude. And Erck has said that if the FDA doesn’t act on these data sets that it could delay approval in the US for months. The NIH-funded trial of the Novavax candidate just got underway in December, and with that start date and the variable case numbers, I can see what he means. I would think that the available data are enough for an EUA myself, and I’m very much in favor of getting another effective vaccine out there, particularly one whose production is likely to ramp up quickly.
I say this because I think we need to continue to get out in front of the variants. Despite a lot of scary headlines, I don’t think that we’ve seen any that really break through the immunity conferred by the current vaccines, but there is, as always, no guarantee that the next one won’t. Here’s a new preprint that looks at T-cell responses to the B.1.1.7, B.1.351, P.1, and CAL.20C variants, and it’s very reassuring: the T-cells raised by the current vaccines can handle these variants just like they can the earlier strains. So as long as that situation obtains, we have to get as many people vaccinated as possible, both to protect the recipients, and to slow down the generation of further variants themselves by cutting transmission.
I stand by the statements that I made at the end of this recent post. I think that we really are winning against the pandemic now, and we can do an even better and faster job of that. But we can also do an even worse and slower job, too, never forget, and it’s vital that we don’t let up now.
