AstraZeneca vaccine raises questions on shot that works better in small doses

Complexity leads to uncertainty in race for vaccine to end pandemic

AstraZeneca’s president of biopharmaceuticals  Ruud Dobber: 'Let’s be a bit more patient and see how the FDA will react'. Picture: University of Oxford

The news reached Sarah Gilbert on Saturday evening that the Covid-19 vaccine she’s developed with AstraZeneca appeared to work. But the University of Oxford professor had expected a key number: Was it more than 90% effective, as others have been — or less?

Instead, when her colleague Andrew Pollard called with the results, he wanted to show her slides rather than simple figures. “I didn’t really understand why we would have to go through slides,” she recalled. “But then it became clear — because it’s rather more complicated in our trial.” 

That complexity has led uncertainty to swirl around one of the front-runners along with Pfizer-BioNTech and Moderna in the race for a shot to end the pandemic. Questions about the most effective dose of the vaccine, its safety record, and the partners’ approach to testing it have cast doubt on whether the US Food and Drug Administration (FDA) will clear it.

Results

Early Monday, AstraZeneca and Oxford reported results after 131 trial participants in the UK and Brazil contracted Covid-19. The average efficacy of 70% prevention sounded good, within the expectations of analysts and above a 50% standard, the FDA had set for Covid vaccines.

The study also found 16 severe cases, all of them among people who didn’t get AstraZeneca’s shot, according to Moncef Slaoui, the former GlaxoSmithKline researcher who heads up the US’s Operation Warp Speed programme. It was good news for Astra’s vaccine programme that had been halted for six weeks in the US while regulators reviewed a serious adverse event that the company never gave details on. Oxford will report details of those adverse events in its efficacy study that it will submit for review in the coming weeks. AstraZeneca shares rose slightly on Tuesday in London after falling 3.8% the previous day. The puzzling part about Astra’s results was that bigger doses were less efficacious. 

Positive data from another vaccine of substantial efficacy with potential advantages in storage, transportation, and affordability will be welcome, said Jesse Goodman, a former head of the FDA’s vaccines office who was later the agency’s chief scientist. “What’s not clear yet is, is this effect a chance observation or does it reflect something that the higher dose may adversely affect immune response,” he said in an interview. “We need more details to begin to understand it.” 

Geoffrey Porges, an analyst with SVB Leerink, was among the most critical voices, calling the data “premature and insufficient”. 

“Let’s be a bit more patient and see how the FDA will react before making such harsh statements,” said Ruud Dobber, AstraZeneca’s president of biopharmaceuticals in an interview with Bloomberg TV.