You may recall that these vaccine trials are set up to get to a defined number of coronavirus cases overall, at which time the various monitoring committees lock the door and unblind the data to have a look at how things are going. Pfizer’s original plan (as mentioned in that post) was the most aggressive of them all – they were planning to take their first look once they hit 32 cases. But one of the things we learned from this morning’s press release is that the company and the FDA changed that, dropping the 32-case read in favor of a 62-case read. By the time they finished those negotiations, though, the number of cases had reached 94, so we actually have a much more statistically robust look than we would have otherwise. And the split between placebo-group patients and vaccine-arm patients is consistent with greater than 90% efficacy. That number will come into better focus, but I hope that we can continue to take 90% as the lower bound.
The final analysis of the trial is set for a 164-case level, and that should be reached sooner than we might have thought. The higher number of cases in this current readout is surely because the coronavirus pandemic is itself at the “uncontrolled spread” stage in much of the Northern hemisphere. Remember the worries about whether companies would have to move their trials around to find places where the disease was still spreading? Seems like a long time ago, and as things have worked out you can (unfortunately) run your vaccine trial pretty much anywhere you like.
More details: these numbers are from 7 days after the second dose of the vaccine (28 days after the first dose overall). Going forward, they plan to collect data at 14 days after the second dose to make the statistics more comparable to the other ongoing vaccine trials. Pfizer/BioNTech say that the protection looks like it should last at least a year – no numbers on that yet, but it can only be based on neutralizing antibody titers and/or T-cell levels and their change over time. The only way to get better numbers on that is to wait and collect better numbers; there is absolutely no way to tell without waiting to see. But if we’re already out to about a year’s protection, that’s very good to hear. And this is the time to mention that nothing has (so far) been set off on the safety side, “no serious concerns”. But the only way to collect longer-term safety data is to keep watching over that longer term as well. I suspect that we’re still going to see plenty of fevers and very sore arms after injection (with this and the other vaccines), and I say bring them on, then.
What does this mean for the pandemic vaccine effort in general? The first big take-away is that coronavirus vaccines can work. I have already said many times (here and in interviews) that I thought that this would be the case, but now we finally have proof. The worst “oh-God-no-vaccine” case is now disposed of. And since all of the vaccines are targeting the same Spike protein, it is highly likely that they are all going to work. There may well be differences between them, in safety, level of efficacy across different patient groups, and duration, but since all of them have shown robust antibody responses in Phase I trials, I think we can now connect those dots and say that we can expect positive data from all of them.
Having the Pfizer/BioNTech candidate read out first has some other implications. One that may (or may not!) get lost in the excitement is that Pfizer explicitly and publicly did not take US government funding for this effort. In fact, they said at the time that working in the “Operation Warp Speed” framework would likely slow them down, and it looks like they can make a case for that! Not all the victory laps that people are going to try to take for this will be justified (and wasn’t that ever the case, right?)
But the other thing to keep in mind is that this candidate has (so it appears) by far the most challenging distribution of all of them. The Pfizer/BioNTech candidate, last we heard, needs -80C storage, and that is not available down at your local pharmacy. Pfizer has been rounding up as many ultracold freezers (and as much dry ice production) as they can, but there seems little doubt that this is going to be a tough one. I know that the press release talks about getting 1.3 billion doses of this vaccine during 2021, but actually getting 1.3 billion doses out there is going to take an extraordinary effort, because you’re getting into some regions where such relatively high-tech storage and handling becomes far more difficult. Population density is as big a factor as electricity and transport infrastructure. With demanding storage requirements, the more people that are within a short distance of a Big Really Cold Freezer, the better. And the more trucks (etc.) that you have to send down isolated roads to find the spread-out patients, the worse. That’s always the case, but if you’re rushing against dry-ice-pack deadlines the situation is more fraught.
What are the regulatory consequences (as discussed here)? The press release says that the companies expect to reach the required safety data (two months after dosing) in the third week of November, and that they plan to file for an Emergency Use Authorization (EUA) after that. The complex rollout of this vaccine itself (see below) may mean that such an EUA, if granted, will not have as much of an immediate effect on the other trials, but this is still an open question, and there seems to be a good deal of debate at the FDA itself about how to handle things. I would assume that any EUA would be directed at the very highest-need populations; we’re not going to see a country-wide effort to vaccinate the population until sometime in 2021.
Remember as well that the efficacy levels we’re seeing this morning are after the second dose. If everyone magically got the vaccine this morning, we still wouldn’t all be able to breath easy for nearly a month. And we are not all getting it this morning, for sure. It’s obvious that the pandemic is ripping through a long list of countries right now – cases are rising steeply, hospitalizations right behind, and although we’re better at treating the patients than we were, deaths are inevitably going up as well. This is all going to get worse before it gets better – but the good news here is that it really is going to get better. Keeping your head down, wearing masks and keeping your distance is more valuable than ever, because there’s an actual finish line in sight that you have to reach. Hang on for the vaccine – for the vaccines – because they really are coming.
We’re going to beat this. We’re starting to beat it right now. An extraordinary, unprecedented burst of biomedical research – huge amounts of brainpower, effort, money and resources – has come through for the world.
