An experimental coronavirus vaccine developed by AstraZeneca and the University of Oxford protected against COVID-19 in two late-stage, placebo-controlled trials of roughly 23,000 participants in the U.K. and Brazil, the development partners said Monday.
An interim analysis after 131 volunteers developed COVID-19 found that, on average, vaccination was 70% effective in preventing the disease. A lower-dose regimen, with a half-dose given first followed by a full dose one month later, was 90% effective, while two full doses appeared 62% effective.
The preliminary results are encouraging and suggest a third experimental coronavirus vaccine works, after positive data from the team of Pfizer and BioNTech, and Moderna earlier this month. AstraZeneca and Oxford's shot uses a different technology than the other two — a signal other vaccines approaches could be effective, too — and is viewed as easier to distribute around the world.
Yet the differing results between dosing regimens are likely to raise questions about how AstraZeneca and Oxford's vaccine triggers the immune system. And the data will be compared to the higher-than-expected efficacy shown by Pfizer and BioNTech and by Moderna, both of which said their vaccines were roughly 95% effective in preventing COVID-19.
AstraZeneca and Oxford's results come from a "pooled" analysis of data from two studies: the COV002 trial, which enrolled 12,390 volunteers in the U.K., and the COV003 study of 10,300 participants in Brazil. The 90% efficacy figure cited by the companies is based on data from a smaller group of 2,741 volunteers who received the lower-dose regimen, while the 62% number is from 8,895 participants who were given the higher-dose regimen.
In each regimen, two shots were given at least one month apart, and protection was measured starting 14 days after the second shot.
Both data points are positive, surpassing, for instance, a 50% minimum threshold for efficacy set by the Food and Drug Administration. But AstraZeneca and Oxford did not share how they averaged the numbers nor how many cases of COVID-19 were observed in either group. Geoffrey Porges, an analyst at SVB Leerink, criticized the 90% estimate as embellished, noting the smaller sample size.
No one who received the vaccine developed severe COVID-19 or was hospitalized, indicating protection against the disease's worst effects. Investigators also noted fewer vaccinated participants developed asymptomatic COVID-19, a finding that, while not conclusive, suggests the shot could help slow the spread of the coronavirus as well.
No severe safety events were confirmed, either, according to AstraZeneca and Oxford, which said they will submit their results to regulators around the world. The partners did not disclose specific data on side effects.
An effective lower-dose regimen would be easier to produce and widely distribute, a potential advantage as demand for an effective vaccine is expected to widely outstrip supply in the coming months.
AstraZeneca expects it can manufacture, along with partners, about 3 billion doses in 2021 — more than either Moderna and the Pfizer, BioNTech team have forecast. Some 900 million of those doses are contracted to be supplied to the U.S., U.K., EU and Japan.
AstraZeneca and Oxford's vaccine also has an important advantage that could aid global distribution. The shot can be stored and transported at normal refrigerator conditions, about 2 to 8 degrees Celsius, or 36 to 46 degrees Fahrenheit. Moderna's and Pfizer and BioNTech's candidates, by comparison, must be transported at ultra-cold temperatures and don't last as long once thawed.
Data are still being collected by AstraZeneca and Oxford, and a larger study in the U.S. is still recruiting volunteers. The initial results, however, appear to fall somewhat below the high bar set by Moderna and the Pfizer, BioNTech team.
Comparing across trials can be difficult, especially early on. Peter Welford, an analyst at Jefferies, noted that Moderna and Pfizer only confirmed suspected cases of COVID-19 after a volunteer reported symptoms, while AstraZeneca and Oxford had stricter criteria, performing mandatory weekly tests on participants to detect coronavirus infection.
AstraZeneca and Oxford also used a meningococcal vaccine as a comparator, rather than a saline injection.
Drugmakers do, however, typically expect their medicines to work better at higher doses, making the differing results reported by AstraZeneca and Oxford somewhat perplexing. The two are using the higher-dose regimen in their big U.S. trial, which is set to enroll 40,000 participants.
Several vaccine experts told the U.K.'s Science Media Centre the difference in protection could be due to the body's immune response to the uninfectious virus used to deliver AstraZeneca and Oxford's vaccine.
"It may seem confusing that a higher initial dose gives a less favorable response, but this may just be due to a residual response in some patients to the disabled 'vehicle' chimpanzee adenovirus used to deliver the vaccine 'payload,' easily fixed by using the adjusted dose," said Stephen Griffin, an associate professor at the University of Leeds in a statement to the Science Media Centre.
The payload delivered by the chimpanzee virus is genetic instructions designed to train the body's immune system to recognize and neutralize the coronavirus. AstraZeneca and Oxford's approach is similar to that taken by Johnson & Johnson, which also has a shot in late-stage testing.
The vaccines from Moderna and partners Pfizer and BioNTech, by contrast, use messenger RNA delivered encased in a tiny bubble of fat.
AstraZeneca and Oxford reported their vaccine was well tolerated across both dosing regimens and that no serious safety events have been confirmed. Testing of the vaccine was paused in September after a participant developed an unexplained illness, but investigators couldn't link that case to vaccination and study resumed.
AstraZeneca said it is preparing submissions to regulators around the world "that have a framework in place for conditional or early approval" and will seek clearance from the World Health Organization to provide the shot to low-income countries.
AstraZeneca, unlike Moderna and Pfizer, has pledged not to profit from sales of its vaccine during the pandemic (although the "pandemic" time period is defined by the drugmaker). Government contracts secured so far suggest a per-dose price of $3 to $4, versus $18 to $20 for Pfizer's shot and $25 to $37 apiece for Moderna's, according to Jefferies' Holford.
Editor's note: This article has been updated to include additional information from the University of Oxford, as well as additional comment.