[But European countries have had
little recourse as Britain used its AstraZeneca doses to deliver a
lightning-fast vaccine drive, bashing back a December surge and promising a far
more normal summer. It has done so with a major dose of flag-waving after a
broader pandemic response that was filled with missteps.]
By Michael Birnbaum, Carolyn Y.
Johnson and Laurie McGinley
Instead, the inoculation, a
collaboration between University of Oxford researchers and one of the world’s
biggest drug companies, has been plagued with missteps as other vaccine
rollouts gain speed. First, there was confusing basic science. Then missed
delivery targets. Now, a confidence-sapping pause in Europe that followed
reports of rare blood clots among a handful of the vaccinated.
If the stakes hadn’t been so high,
the AstraZeneca saga might have felt like a soap opera, with soaring moments of
scientific brilliance undercut by embarrassing mistakes. The Oxford team that
developed the vaccine was bold — but also appeared arrogant to many scientists
on both sides of the Atlantic.
Had the rollout of the AstraZeneca
vaccine been handled differently, it might have been available far more widely
by now, blunting a new wave of death and disease that is threatening lives
around the world. Countries that have administered it widely, such as Britain,
credit AstraZeneca with helping drive a dramatic drop in hospitalizations and
deaths. But public confidence in the company’s vaccine has taken a major hit,
slowing its acceptance and delaying the battle against the pandemic.
Nowhere have the consequences been
clearer than in Europe, which bet heavily on AstraZeneca vaccine doses but has
received just a third of what was promised. Now, many countries are shutting
down yet again as the more contagious coronavirus variant first spotted in
Britain races across the continent. Hungary broke records for deaths and cases
Friday. France imposed a strict new shutdown in much of the country. Germany’s
cases were up 50 percent last week. And opinion polls suggest public
willingness to get an AstraZeneca vaccine is dropping.
“AstraZeneca has unfortunately
underproduced and underdelivered,” European Commission President Ursula von der
Leyen told reporters last week. “And this painfully, of course, reduced the
speed of the vaccination campaign.”
AstraZeneca declined to comment on
the record for this article, but pointed to a statement after European Union
regulators reaffirmed the vaccine’s safety last week following review of the
reports of blood clots.
The benefits “continue to far
outweigh the risks,” the company said in the statement. “Analysis of
AstraZeneca’s safety database on tens of millions of records for [the vaccine]
did not show that these events occurred any more commonly than would be
expected in millions of people.”
Bumpy science
The AstraZeneca vaccine surfed a
wave of hype last spring. A front-page article in the New York Times declared
that the Oxford vaccine was “sprinting fastest” and had leaped ahead of everyone
else. Oxford scientist Sarah Gilbert said at the time she was 80 percent confident the vaccine
would succeed — before a single person had received a shot in a clinical trial.
“From the very beginning, the
Oxford group was having one press release after another, bragging how wonderful
everything was,” said Hildegund C.J. Ertl, a scientist who works on the same
vaccine technology at the Wistar Institute in Philadelphia and has collaborated
with the Oxford scientists. “Talking about how wonderful something is before
you’ve shown it is completely counterproductive. It was a big PR disaster.”
Adrian Hill, a key member of the
Oxford team that developed the vaccine, argued that the early communication on
the shot was accurate — and partly a response to Anthony S. Fauci, director of
the National Institute of Allergy and Infectious Diseases, who predicted a
coronavirus vaccine could be ready in 12 to 18 months.
“We disagreed. We said we’d shoot
for September, and it’ll be this year. If that’s boastful, I’m sorry, but that
was right,” Hill said in an interview. “We were frankly saying this could be
done much faster.”
The scientists framed their work as
a global solution — not just a shot for rich nations. AstraZeneca said it would
not seek a profit on doses it made. It priced them at about $4 a shot — as
little as a fifth of that of some of its competitors. The doses could be stored
in ordinary refrigerators, unlike those from Pfizer-BioNTech and Moderna,
making them easier to administer in developing countries with vulnerable health
systems.
In May, months before rival vaccine makers Moderna or Pfizer-BioNTech launched large
clinical trials, Oxford and AstraZeneca announced they would test their vaccine
in 10,000 people in Britain.
Shortly after, the United States
announced it would spend up to $1.2 billion for 300 million doses
from the company that would begin to be available in October — the biggest
initial U.S. order for a vaccine. But before shots could be administered in the
United States, the AstraZeneca vaccine would need to be tested in a
30,000-person trial, a choice scientists made to ensure that multiple American
vaccine trials would be roughly comparable — and large and diverse enough to
adequately measure the safety and efficacy of the vaccines in many groups of people, including older adults
and groups hit hardest by the pandemic. The trial wouldn’t begin until the end of August.
Even as Oxford’s trials raced
forward, they hit snags. Rare neurological symptoms occurred in three people,
two of whom received doses of the study vaccine, causing trials to be suspended
worldwide to explore whether those might have been caused by the vaccine. There
was no evidence of a connection, but the pause went on for weeks in the United
States, setting the trial back.
Then some participants in the
British trial unexpectedly received a first dose only half as strong as
initially planned, and the explanations about why it happened were confusing,
contradictory and slow to emerge. The problem appeared linked to an Italian
subcontractor that used a different technique to measure the vaccine’s active
ingredient.
Hill said researchers received
regulators’ approval to give a new dose to trial recipients, and insisted that
there was no mistake.
After the dosing error was
revealed, the AstraZeneca team gave different explanations. Andrew Pollard, one
of the lead Oxford research scientists, told The Washington Post last month:
“It’s framed as an error, but actually it’s a scientific observation.”
That dosage issue later became a
point of confusion when the company released trial results to the world in
November. In the half-dose group, the efficacy of the vaccine shot up to
90 percent, compared with 62 percent in volunteers who received the
full two-dose regimen.
The Oxford scientists were frank
that they couldn’t explain why the unconventional dosing group had superior
protection and said they were exploring explanations.
Ultimately, it became clear that instead
of a four-week gap between shots, some participants in the half-dose group had
received shots as much as three months apart, which could have explained the
difference.
“We need to understand what’s
behind it scientifically,” Moncef Slaoui, then the chief science adviser to
Operation Warp Speed, said at a briefing.
U.S. scientists have expressed
frustration about trying to understand how well the vaccine works and how to
best use it given the existing data and confusing communication.
“The bottom line is the
communication has not been good. And I don’t know whom to attribute that to,
but clearly companies, especially vaccine development companies, have to have
clear communication practices,” said Stanley Plotkin, inventor of the rubella
vaccine. “And so there’s been misunderstanding, difficulty, even from the point
of view of science, to understand what’s going on.”
Perhaps most important, some
scientists say, the AstraZeneca team decided not to emphasize recruitment of
older people for their initial clinical trials in the United Kingdom, and so no
robust conclusion could be made about how well the vaccine protected people
older than 65 — the group most at risk of serious illness.
“AstraZeneca has had some bad press,
most of it undeserved, but some of it deserved,” said Paul Hunter, a professor
of medicine at the University of East Anglia in Britain.
The company has defended its
trials, saying its scientists were being cautious. But human studies by
Pfizer-BioNTech and Moderna included plenty of older volunteers. The absence of
data led some European countries to recommend against giving doses of the
vaccine to older citizens.
Hill said if he could do things
over, he wouldn’t change much — with the exception of potentially looking at
the data even earlier, so that a vaccine could have been shown effective in
August. He questioned why the AstraZeneca vaccine had to be subjected to
further trials before being authorized in the United States.
“People are dying out there,” Hill
said. “Why are they so hopelessly slow?”
European frustration
Europe bought into AstraZeneca’s
promises that its vaccine would be a swift, effective solution, making it the
centerpiece of a collective purchasing strategy negotiated on behalf of the
E.U.’s 450 million residents. The European Commission bet heavily on AstraZeneca:
300 million doses in a mid-August contract, more than other vaccines.
European officials expected
AstraZeneca’s vaccine to be ready first. But as fall edged into winter — and a
deadly second wave washed away complacency — that started looking like a bad
bet.
AstraZeneca was approved in the
European Union at the end of January, six weeks later than rivals, at a time
when a more contagious variant of the coronavirus was spreading across the
continent and every day mattered. Compounding the already-delayed rollout,
AstraZeneca chief executive Pascal Soriot had an unwelcome surprise for the
Europeans: The bloc was supposed to receive 90 million doses by the end of
March but would get only 30 million. Later, the company said its
second-quarter delivery would fall short, too.
Europe erupted. There had been
little warning — and in Britain, which approved the AstraZeneca vaccine a month
earlier than the European Union, there had been no supply issues. E.U. leaders
asked why.
“Everybody is getting kind of a
bit, you know, aggravated or emotional about those things,” Soriot told Italy’s
La Repubblica newspaper in an interview published Jan. 26. “It’s not a
commitment we have to Europe. It’s a best effort.”
Von der Leyen, who as European
Commission president had presided over the vaccine negotiations, imposed new
rules that drug manufacturers needed to ask for permission before exporting
E.U.-made vaccines outside of the bloc’s territory. Italy threatened to sue
AstraZeneca for breach of contract. Latvian Foreign Minister Edgars Rinkevics
vowed to “get nasty” in a late-January interview with The Post.
But European countries have had
little recourse as Britain used its AstraZeneca doses to deliver a
lightning-fast vaccine drive, bashing back a December surge and promising a far
more normal summer. It has done so with a major dose of flag-waving after a
broader pandemic response that was filled with missteps.
On a visit to a lab, “I could tell
from the excitement of the scientists that this was promising and that the
Oxford-AstraZeneca vaccine looked as though it would work,” British Prime
Minister Boris Johnson wrote last week in an editorial in the Times of London.
He was vaccinated Friday.
Even as Europe fought to get access
to the AstraZeneca vaccine, leaders were undermining public confidence in the
shot — a contradictory process that culminated with the pause in vaccinations
last week.
In Denmark, Germany, Norway and
elsewhere, regulators spotted reports of serious or fatal blood clots among
young people who had been given doses of the AstraZeneca vaccine. They were just
a handful — in Germany, seven people at the beginning of the week, out of
1.6 million people given doses of the vaccine in a month.
But regulators said it was
statistically significant and halted vaccinations to investigate. Once Germany
stopped, most other countries did the same, even though E.U. regulators and the
World Health Organization begged them to keep going as they investigated.
In France, only residents younger
than 65 were initially eligible for the vaccine, because the data for the
elderly was so sparse. Then it expanded eligibility to include people up to 74.
After Germany briefly suspended AstraZeneca’s use last week, France suddenly
followed suit. On Friday, it gave a green light to use the vaccine again — but
only for those 55 and older, because the blood clots were spotted mostly in
younger people.
Through it all, the top E.U.
regulator has been consistent: The shot is safe for everybody.
But the lurching back-and-forth has
damaged public perceptions. Even before the uncertainty about the blood clots,
teachers and medical workers unions in multiple countries had demanded Pfizer
vaccine doses instead of AstraZeneca ones.
Vaccinations resumed Friday after
Europe’s top regulator declared a day earlier that the advantages outweigh the
risks.
Experts warned the public image of
the vaccine would take a permanent hit. According to a survey poll by the Elabe
Institute, a polling firm, published
last week, almost 60 percent of the French said they do not trust the
AstraZeneca vaccine, compared with 25 percent who said the same about the
Pfizer shot. Polls in other countries show similar drops in confidence.
Global consequences
Amid the turmoil, some countries
are abandoning their AstraZeneca purchases. New Zealand this month decided not
to use its AstraZeneca order, opting to vaccinate exclusively with Pfizer’s
vaccine and donate other manufacturers’ doses to countries that don’t have
their own access. South Africa sold its AstraZeneca doses after researchers
concluded it provides only “minimal protection” against mild to moderate
covid-19 cases caused by the variant discovered in the country.
Other countries are still seeking
out AstraZeneca doses: Australia and Canada are trying to buy more. And the
United States sent some of its stockpile to Canada and Mexico last week, amid
growing questions about the future of the doses in U.S. vaccination plans.
In the United States, an
accelerating inoculation campaign is being fueled by three vaccines in
increasingly plentiful supply: Pfizer-BioNTech, Moderna and Johnson &
Johnson, raising questions about the need for another option. AstraZeneca’s
fate depends on a 30,000-person, late-stage clinical trial being conducted at
multiple sites in the United States.
The data is expected any day, after
which the company is expected to apply to the Food and Drug Administration for
emergency use authorization. The agency could clear the vaccine in late April
or May.
At least, that’s the plan. But it
remains uncertain.
The FDA will be sure to scour the
data for signs of the rare complications reported in Europe. If the results
confirm the shot is safe — as the top European regulator asserts — then a
bigger hurdle for the vaccine may be its efficacy.
If the U.S. study data shows the
two-shot AstraZeneca product is less effective than the one-dose Johnson &
Johnson vaccine, that raises an obvious question: Should the AstraZeneca
vaccine be cleared, given the United States already has three effective
vaccines?
Biden administration officials
already are debating that question and the best course for public health in the
United States and around the world.
The two-dose Pfizer and Moderna
vaccines have efficacy of about 95 percent, according to clinical trial
data. The Johnson & Johnson one-shot vaccine is 66 percent effective.
The 62 percent efficacy rate for AstraZeneca is for the protocol now being
used in the U.S. trial — two doses a month apart.
Within the FDA, there was some
discomfort about Johnson & Johnson’s lower overall efficacy compared with
Pfizer and Moderna, even though the shot cleared the 50 percent bar required
for coronavirus vaccine authorizations. But those concerns were far outweighed
by the appeal of a single-dose regimen, which offers tremendous savings of time
and resources, and the vaccine’s high effectiveness against serious illness and
death.
If the AstraZeneca vaccine shows
similar protection against severe illness, U.S. regulators may be inclined to
wave it through, even if they are disappointed in its overall efficacy, some
experts suggested.
Some said the United States does
not need the AstraZeneca vaccine, no matter what its efficacy. President Biden
has said there will be enough vaccine doses from Pfizer-BioNTech, Moderna and
Johnson & Johnson by the end of May to inoculate all U.S. adults.
“I don’t see any role for the
AstraZeneca vaccine in the U.S.,” said Eric Topol, founder and director of Scripps
Research Translational Institute. He hopes the U.S. study data will be good,
that the FDA will authorize the vaccine and that the administration then will
donate it to Covax, a global vaccine initiative linked to the WHO.
Elsewhere, the calculation involving
AstraZeneca is far different. And in the European Union, where cases are up
30 percent in the past two weeks, policymakers say there is a desperate
need for vaccinations.
“This is a safe and effective
vaccine,” European Medicines Agency Director Emer Cooke told reporters as she
cleared AstraZeneca for use. “If it were me, I would be vaccinated tomorrow.”
Birnbaum reported from Riga, Latvia;
Johnson from Boulder, Colo.; and McGinley from Washington. William Booth in
London, Quentin Ariès in Brussels, and Loveday Morris and Rick Noack in Berlin
contributed to this report.