How AstraZeneca and Oxford blew their big moment: A messy week that overshadowed what should have been a scientific victory

  • AstraZeneca and the University of Oxford said that their coronavirus vaccine succeeded in a trial.
  • But some of the information they disclosed in press releases raised questions.
  • The scrutiny centered on a lack of information in two areas: how well did the vaccine work? And how safe was it?
  • AstraZeneca is planning to further investigate the alternative half-dose-full-dose dosing regimen, as it asks some regulators to sign off on it.
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Early on Monday, AstraZeneca and the University of Oxford announced preliminary results from a trial of their coronavirus vaccine.

It should have been a moment of triumph.

They said the vaccine was 70% effective, on average, at preventing COVID-19, the disease caused by the new coronavirus that's swept the world. That surpassed standards that some regulators have set for approval, though it lags behind results from two other experimental vaccines.

But some of the information, disclosed in press releases, raised questions. The researchers provided little information about how they arrived at that efficacy figure, which combined data from different trials. Scientists also questioned how the company described the safety of the vaccines.

"The transparency and the quality of communications are probably almost as important as the results," said Dr. Jesse Goodman, a former top scientist at the US Food and Drug Administration who's now a professor at Georgetown University.

'Ups and downs'

"If scientific experts are confused by what's out there, I'm also concerned that the sort of ups and downs and changes in communication from day-to-day could be confusing to the public and undermine their confidence," he added.

AstraZeneca's results followed announcements from Pfizer and Moderna that their coronavirus vaccines had succeeded in late-stage studies. Both companies said in press releases that their shots were about 95% effective at preventing COVID-19.

All three vaccine frontrunners are still experimental. None of the programs has published late-stage results in a medical journal, and regulators in the US, UK, and Europe have not authorized any of the shots to be used.

But Moderna and Pfizer have put out more information on how their trials were being run along the way, and the press releases they've put out so far were perhaps more informative. Plus, each one is running a single large trial, a less complicated design than the Oxford-AstraZeneca research.

Read more: How the pharma giant Pfizer teamed up with a little-known biotech to develop an effective coronavirus vaccine in record time

To be clear, if they get the green light from regulators in the coming weeks, all three vaccines could prove to be useful tools against a pandemic that's killed more than a million people and slammed the global economy. And the world will need several different vaccines to immunize a significant portion of the global population, because each company is limited in how many it can produce.

'A mixed bag'

Still, among outside experts, the lack of information from Oxford and AstraZeneca on their vaccine drew skepticism almost immediately.

JPMorgan analysts called the disclosures "a mixed bag." John LaMattina, a former Pfizer executive, called the results "odd," and said they would delay the use of the vaccine. Geoffrey Porges, a biotechnology analyst at SVB Leerink who trained as a physician, leveled harsher criticism.

"We regard the data disclosure as premature and insufficient, and is likely to attract a raft of criticism," he wrote. He said he doubted that the vaccine would ever gain US approval.

The questions centered on a lack of information in two areas: how well did the vaccine work? And how safe was it?

On safety, the AstraZeneca release raised questions by saying that no safety problems had been "confirmed." AstraZeneca also didn't release new information on the side effects of the shot, though researchers had previously published some data from about 560 participants in the UK trial in the medical journal The Lancet.

There had been at least one publicly-known safety problem along the way. In September, all trials were put on hold following an unexplained illness in one of the UK participants. By the end of October, all trials were underway again, but AstraZeneca's Monday statement didn't provide more information on the episode.

On efficacy, outside experts puzzled over why the vaccine was 62% effective in one group, and 90% in another, an unexpected finding. AstraZeneca said it averaged those figures to arrive at the vaccine's overall effectiveness of 70%.  

The vaccine was 90% effective in a group of people in one of the trials who got an unusual regimen by accident: half a dose of the shot, followed by a full dose a month later. Others got two full doses of the shot.

Moncef Slaoui, chief adviser to Operation Warp Speed.AP Photo/Evan Vucci

A drip of disclosures raises questions

Without a peer-reviewed scientific paper laying out how the data was analyzed, it's unclear how they've crunched the numbers, Goodman said

"You can't do studies and then pick and choose results or groups from different studies," Goodman said. "You sort of need to live with the whole of all the data."

Soon, a disclosure about the group that got the half-dose-full-dose regimen raised eyebrows further. A top AstraZeneca exec told Reuters that the half-dose-full-dose regimen was actually given to participants by accident. The company hadn't disclosed that information in its press release.

The drip of information continued.

On Tuesday, Moncef Slaoui, the scientific head of the US vaccine effort known as Operation Warp Speed, added a couple details that confirmed concerns about the Oxford-AstraZeneca data. 

In a briefing to reporters, he revealed that there was a key difference between the group that got the half-dose-full-dose regimen and others in the trial: they were younger, no older than age 55. Vaccines sometimes don't work as well in older people.

'We need to understand what's behind it scientifically'

Slaoui also cautioned that it was possible, but unlikely, that the efficacy difference between the groups could be chalked up to random chance, because it happened in a relatively small subset of the trial, and because of other variables at play, such as the age difference.

"We need to understand what's behind it scientifically," he said.

The week's drip of information concerned Dr. Paul Offit, a top vaccine researcher at the University of Pennsylvania.

"Maybe there's promising data with this vaccine, but you have to be honest with people," he said in a Friday interview. He also said he's worried about how alack of clarity could affect trust in other vaccines, as well as in AstraZeneca's.

By Thursday, AstraZeneca had beat something of a retreat. Pascal Soriot, the company's CEO, told Bloomberg News that the company would further investigate the half-dose-full-dose regimen. He said he still expected to press forward with requests for regulatory approval in the UK and European Union. 

US authorization will have to wait for a trial currently underway in that country, Bloomberg reported. Morgan Stanley analysts said they expect that trial to deliver results later this year or early in 2021.

'There's something interesting here'

In the long run, the mistake made by workers testing the AstraZeneca-Oxford vaccine could prove fortuitous if it reveals a better way to give the immunization, said Deborah Fuller, a microbiologist at the University of Washington who works on treatments and vaccines for viruses. But there's a need to investigate it more fully and understand the reasons behind it, she said.

"Let's put the mistake aside and look at the data because there's something interesting here," she said.

We should get that data soon. AstraZeneca has said it plans to publish more detailed information in a scientific journal, opening its data up to public scrutiny from outside scientists.

Even if the AstraZeneca-Oxford shot turns out to be 62% to 70% effective, it could still be an important tool in the fight against the coronavirus. Chiefly, that's because AstraZeneca has promised to pump out far more of the shot than Pfizer or Moderna, at a significantly cheaper price, as little as $3 to $4 a shot, which could make it available to more of the world's population. 

"The vaccine's simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available, supplying hundreds of millions of doses on approval," Soriot said in a statement.

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