AstraZeneca Defends Dosing Error in Covid-19 Vaccine Trial
November 25 2020 - 10:16PM
Dow Jones News
By Joseph Walker and Jenny Strasburg
A top executive at AstraZeneca PLC pushed back on Wednesday
against criticism that the company failed to disclose enough data
from a clinical trial of its Covid-19 vaccine earlier this week,
and acknowledged skepticism about the vaccine's 90% effectiveness
in a group of patients who were accidentally given a lower dose
than intended.
"I'm not going to pretend it's not an interesting result,
because it is -- but I definitely don't understand it and I don't
think any of us do," said Mene Pangalos, AstraZeneca's executive
vice president for biopharmaceuticals research and development. "It
was surprising to us."
The U.K. company said on Monday that the vaccine it is
codeveloping with the University of Oxford was on average about 90%
effective in preventing Covid-19 when volunteers were given a
half-dose shot followed by a full dose a month or more later, but
only 62% effective when two full doses were given. The data pooled
trial results from the U.K. and Brazil.
U.S. regulators have set the bar for authorizing vaccines at 50%
effectiveness, but vaccines in development by Moderna Inc., and
partners Pfizer Inc. and Germany's BioNTech SE have set the
benchmark even higher with study results showing greater than 90%
effectiveness. Those vaccines use a new gene-based technology that,
despite its impressive clinical results thus far, requires the
shots to be stored at subzero temperatures. AstraZeneca's vaccine
can be stored in a more standard refrigerator, which could make it
attractive to low- and middle-income nations.
In the days since the results were announced, independent
scientists and U.S. government officials said the data is further
proof that vaccines can prevent Covid-19, but they also cautioned
that the 90% effectiveness rate might not hold up under further
analysis.
AstraZeneca on Monday said in interviews with news media that
the half-dose regimen was the result of a manufacturing error,
which neither the company nor Oxford initially mentioned in their
press releases announcing the results.
The dosing error was identified after a trial investigator
noticed that volunteers weren't having as much of an inflammatory
response to the shot, prompting the researchers to analyze their
vaccine supply and find that they had miscalculated the dose, Dr.
Pangalos said.
AstraZeneca and Oxford informed regulators in the U.K., U.S.,
and European Union and amended the study design to include the
half-dose group in their analysis.
"The mistake is actually irrelevant," said Dr. Pangalos.
"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."
Oxford researchers said on Monday that the lower dose may have
been more effective because it more accurately reflects the natural
immune response to viruses, but that they would have to investigate
the findings further to know for sure.
Other factors could also be at play. The half-dose was only
given to volunteers 55 and younger, whereas the full-dose group
also included older patients, said Dr. Moncef Slaoui, chief
scientific adviser to the U.S. government's Operation Warp Speed
initiative, on a call with reporters on Tuesday, the first
disclosure of the lack of older participants in the half-dose
group. It is also possible that the difference between the groups
was a statistical fluke and the result of chance, he said.
"There are a number of variables that we need to understand,"
said Dr. Slaoui. "It's unlikely but it's still possible that it's a
random difference."
AstraZeneca plans to test the half-dose regimen in a large,
ongoing U.S. study expected to enroll more than 30,000 volunteers,
Dr. Pangalos said. The study has enrolled more than 11,000
volunteers and could have results soon given the progression of the
pandemic, Dr. Slaoui said.
Dr. Pangalos said there is a theoretical rationale for why a
lower first dose might work, but that he wouldn't speculate until
the researchers investigate the data further. "I'm not going to
hand wave with the immunologists," he said. "Until I see some data
that gives me some science behind it, I'm going to say 'I don't
know.'"
Some scientists have criticized AstraZeneca for not revealing
key data from the trial results, such as how the number of
infections that occurred across patient groups and broken down by
age and severity of disease -- though the company did say that no
patients receiving the vaccine developed severe disease or required
hospitalization.
"AstraZeneca provided very little real information for one to
independently assess how their vaccine trials are doing," said
Shane Crotty, a vaccine and infectious diseases researcher at La
Jolla Institute for Immunology. "It's quite reasonable for people
to be skeptical."
Dr. Pangalos said the researchers only received the data last
weekend and are working to quickly release the full data in a
peer-reviewed journal. "The right way of publishing and documenting
the results is in a scientific journal, and these data will all be
published within the next week or so," he said.
Write to Joseph Walker at joseph.walker@wsj.com and Jenny
Strasburg at jenny.strasburg@wsj.com
(END) Dow Jones Newswires
November 25, 2020 22:01 ET (03:01 GMT)
Copyright (c) 2020 Dow Jones & Company, Inc.
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