When the British-Swedish drugmaker AstraZeneca announced on Monday that its experimental coronavirus vaccine is 70% effective on average, the world exhaled a collective sigh of relief and stocks rallied. Another vaccine with promising results had arrived.
But a lack of clarity surrounding several aspects of the data from the AstraZeneca vaccine trials have raised some eyebrows in the scientific community, potentially setting back the timing for the vaccine to be authorized in Europe and the US.
AstraZeneca said on Monday that study participants in the UK had been given two different courses of the vaccine.
The drugmaker, which developed the vaccine with the University of Oxford, did not however, at the time, explain why they used two different dosing regimens or why the size of one group was significantly smaller than the other.
In one group, 2,741 participants received a half-dose of the vaccine and then a full dose at least a month later. This group was 90% protected against Covid-19.
In the second group, 8,895 participants received a full dose followed by another full dose at least a month later. This group was only 62% protected.
That’s why AstraZeneca says their vaccine is 70% effective, on average.
But some scientists are questioning why the company would report on a pooled result of two different trials, as it deviates from standard reporting on clinical trials.
And in the days following that announcement, another point of confusion has emerged.
On Tuesday, Mene Pangalos, AstraZeneca’s Executive Vice President who heads up non-oncology research and development, first explained to Reuters that a lab error was the reason why some volunteers had received a smaller dose – the dose that proved to be 90% effective. “The reason we had the half dose is serendipity,” Pangalos said, adding that researchers had “underpredicted the dose of the vaccine by half.”
In a statement on Wednesday, Oxford’s communications manager for vaccines told CNN that “dose selection for any new vaccine is a complicated area, and in exploring methods of dose selection, we discovered one gave a lower dose than expected.”
Oxford elaborated further on Thursday, saying in a statement to CNN that a “difference in the manufacturing process” had led to the error.
That manufacturing problem has since been corrected, the statement said, noting that the UK regulator overseeing the trial had agreed to include “both approaches” in Phase 3.
While AstraZeneca and Oxford face criticism about transparency – given that they did not mention the error in their press release announcing the results nor on a press call on Monday – the company believes the world should focus on the trial’s positive results.
Speaking to the Wall Street Journal on Wednesday, Menelas Pangalos AstraZeneca’s Executive Vice-President said, “The mistake is actually irrelevant.
“Whichever way you cut the data – even if you only believe the full-dose, full-dose data… We still have efficacy that meets the thresholds for approval with a vaccine that’s over 60% effective,” Pangalos said, according to the WSJ.
AstraZeneca and Oxford have yet to put forward a candidate for interview, as requested by CNN.
The US Food and Drug Administration requires a threshold of at least 50% efficacy. It is not clear if the FDA will authorize emergency use however.
AstraZeneca has not yet tested its half-strength dose in the US either. But on Thursday, a spokesperson for the company told CNN their aim was to include the half-strength dose regimen into their US trials, which currently has around 10,000 participants.
The spokesperson said that the company hopes to recruit around 40,000 volunteers in total – some of whom would receive the half-dose vaccine. They added that they were in “ongoing discussions” with the FDA for approval, adding that nothing formal had been announced.
On Monday, Dr. Paul Offit, a member of the FDA’s Vaccines and Related Biological Products Advisory Committee – which will review Covid-19 vaccines before they are put on the market – said the lack of data that led them to their conclusions made it “hard to know the significance of their findings.”
When two other major drugmakers, Pfizer and Moderna, released their efficacy results earlier this month, they did include the data that led to their results.
AstraZeneca presented an analysis of 23,000 participants in its Phase 3 trial.
It said some participants received the Covid-19 vaccine, while others received a different vaccine for an unrelated virus, or placebo injections.