Eager to redeem its Covid-19 vaccine, AstraZeneca touts 82.4% efficacy for 12-week dosing schedule — but will the FDA buy it?
AstraZeneca and Oxford say they now have clinical evidence that dosing their adenovirus-based Covid-19 vaccine 12 weeks apart — a regimen approved by the UK, perplexing many — can actually render the shots more effective.
The data will be key to AstraZeneca’s attempt to pull itself back to the upper ranks of the vaccine hierarchy, where it’s struggled as skeptics poke holes in its efficacy while production delays trigger heated disputes with the EU. But it remains to be seen what impact, if any, the analysis will have on the FDA’s thinking and decisions regarding the vaccine.
The new results draw from the same Phase III study, conducted in the UK, Brazil and South Africa, whose interim data cemented the first authorizations of the vaccine, but include 332 cases of Covid-19 (compared to 131 at the initial cut).
Investigators wrote in a preprint on the Lancet:
In our study, vaccine efficacy was higher, after the second dose, in those with a longer prime-boost interval, reaching 82.4% in those with a dosing interval of 12 weeks or more. Point estimates of efficacy were lower with shorter dosing intervals, though it should be noted that there is some uncertainty as confidence intervals overlap. Higher binding and neutralising antibody titres were observed in sera at the longer prime-boost interval, suggesting that, assuming there is a relationship between the humoral immune response and efficacy, these may be true findings and not artefacts of the data.
In total, 1293 participants (out of 17,177 included for this analysis) were given two full doses of the vaccine 12 weeks apart.
If true, it confirms earlier suggestions by AstraZeneca execs — backed by some scientists — that the 12-week interval is the “winning formula” for getting efficacy near the levels of the Pfizer/BioNTech or Moderna vaccines.
While there’s still some distance between 82.4% and 95% (as reported by the mRNA players), the difference is notably smaller than when investigators observed a 62% efficacy for two full-dose regimen, administered 4 weeks apart.
Will it matter outside of the UK and the EU, where the authorities already recommend the longer dose schedule?
Biopharma R&D chief Mene Pangalos admitted in a media briefing Wednesday morning that the US Phase III trial, which he believes the company needs to complete before seeking an emergency use authorization from the FDA, only tests the 4-week dose interval. The label and recommended implementation is a whole other matter.
“Obviously we do want the FDA and regulators to be informed by our data on inter-dose intervals from our other global studies,” he added.
Interestingly, investigators proposed that the longer dosing schedule may be somewhat responsible for the early subgroup analysis that found a low dose followed by a high dose — given to around 8,000 volunteers by error — was much more effective, boosting efficacy to 90%.
“This finding is confirmed in the current analysis, but with further data available, we show that the enhanced immunogenicity and efficacy with this regimen may be partly driven by the longer dosing interval that was a feature of this group, further supporting the observation of a relationship between dose interval and efficacy in the SD/SD group discussed above and supported by emergency use authorisation,” they wrote, adding: “The SD/SD regimen is preferred operationally as it is more straightforward to deliver a vaccine with one dosage, and because there are more immunogenicity and efficacy data to support its use.”
AstraZeneca has previously said it would conduct a new trial to test that regimen, but they have now dropped that plan to focus on the longer interval and next-generation candidates.
“Our ambition is to be ready for the next round of immunizations that may be necessary as we go into next winter,” he said. “That’s what we’re aiming for.”
Add that to the newly reported number that the AstraZeneca vaccine is 76% effective after just one shot, and it’s also a boon for countries that are scrambling to put vaccines in arms, giving them more time to sort out the first doses for more people before having to worry about the second dose.
The company added that new data confirmed that its vaccine could prevent hospitalizations or severe cases, reaching 100% protection if you start counting 10 days after the first dose. In the same period, the control group saw 22 such events.
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