[jyl]

AstraZeneca press released interim data from UK and Brazil phase 3 trials. The data is a little weird, because they used two dosing regimens which produced very different efficacy. Two full doses (full dose to prime, then another full dose to boost) had efficacy 62%. Half dose then full dose had efficacy 90%, but this was in a small subgroup of just 2,741 subjects.

They did not release detailed data or statistical measures, so we don't know how robust those numbers are. The data is based on 131 events (infections) in the first 11,400 trial subjects. The event numbers in the half/full dose group would have been very small (2?). AZN didn't disclose the statistical strength of the claimed 90% efficacy in the half/full dose group - or the 62% efficacy in the full/full group.

Some subjects were in the UK trial, which had some patients on full/full dosing and some on half/full dosing. In the UK trial, subjects were PCR tested weekly, which means they'd be more likely to detect asymptomatic or near-asymptomatic cases. Others were in the Brazil trial, which had all patients on full/full dosing. In the Brazil trial, subjects were tested for infection if they reported symptoms, which means they probably would not detect asymptomatic cases. These different protocols further muddy the waters.

The US phase 3 trial is continuing. It uses the full/full dosing and tests for infection if the subject has symptoms, similar to the Brazil trial. AZN says it is talking to the FDA about changing the US trial to include some half/full dosing.

So all that is pretty confusing and a lot of questions remain. But, here's the good:
- AZN's vaccine is stable for 6+ months in a normal refrigerator
- other than the one case of reported transverse myelitis (about which little has been disclosed), the adverse reactions seem modest
- they expect to make 3 billion doses in 2021
- they have licensed the vaccine to Serum India and other drugmakers who can make more (my est: 1-2 billion doses)
- they have committed to sell the vaccine at cost ($2.50-4.00) during the pandemic (so, for 2021 at least) before potentially raising the price to commercial levels.

There is a good deal of speculation that the reason for the worse efficacy of the full/full dosing is that the subjects acquire immunity to the vector virus (a chimpanzee adenovirus) after the first dose, and that immune response reduces the effect of the second dose. One of the Chinese companies used a human adenovirus as their vector and saw a lot of problem with pre-existing immunity to that vector, in phase 1 or 2 trials I recall they saw antibodies to the SARS2 virus generated in only 50% of trial subjects. China has pushed that vaccine to ph 3 trials anyway. AZN was trying to avoid that problem by using the chimpanzee adenovirus, there's a question if they fully succeeded. Note also that IF the vaccine needs to be re-administered annually, AZN may be out of luck - they may not get the "recurring" business.

It would have been better to see a very high efficacy and less confusing "data" (remember, so far merely a press release). Still, it seems very likely this vaccine will be approved and used and help a lot in controlling the pandemic. It also seems fairly likely that countries who are rich enough to afford the PFE or MRNA vaccines, and got their orders in quickly enough, will want to use more of those and rely less on AZN's vaccine.

I remember, very early in all this, I asked which vaccine people would choose to get if they had a choice. This was many months ago, when only spotty phase 1 data was available. Only one person answered , that was RWebb who said without hesitation that he'd definitely choose one of the mRNA vaccines. I guess that's the actual expertise showing through . . .

We should start talking about the vaccine logistical plans and how to get higher on the vaccine priority list. I'm not saying that I would want to jump the line ahead of grandma, but I'd prefer not to get my shot after the "good stuff" has all run out . . .