Fortune or foresight? AstraZeneca and Oxford stories clash over COVID-19 vaccine

LONDON (Reuters) – AstraZeneca and the University of Oxford have given conflicting accounts of how they discovered the most effective dosing schedule for their COVID-19 vaccine, a rare example of public dissent between major collaborating institutions to a pivotal project.

The deviation, first reported by Reuters, centers on the regimen given to a smaller group of volunteers in late-stage trials of half a dose followed by a full dose. This deviated from the initial plan of two full doses, administered to the majority of participants.

The half-dose regimen was found to be 90% effective, compared to the 62% success rate in the main two-full-dose study, based on interim data.

AstraZeneca’s research chief told Reuters 10 days ago, when provisional data from the trials were released, the half-dose was inadvertently given as the first injection to some trial participants and emerged like a fluke – a “fluke” – that scientists have exploited expertly.

This account was refuted by a leading scientist at the University of Oxford, who told Reuters on Monday that the half-dose vaccine was given on purpose after extensive consultations.

Uncertainty as to how the dosing regimen came about raises questions about the robustness of the data, according to some experts who said it could slow the process of getting regulatory approval for the shot and hurt the results. public confidence.

“These different accounts are disturbing,” Eleanor Riley, professor of immunology and infectious diseases at the University of Edinburgh, told Reuters.

“Trust is paramount when it comes to vaccines and we must not do anything that could in any way compromise it.”

There’s also the potential impact on AstraZeneca, whose shares underperformed rival vaccine developers who also reported positive results, in part due to scientists’ concerns about the relatively small sample size of the sub. -Half-dose group which led to an efficacy of 90% discovered.

AstraZeneca declined to comment on the conflicting accounts.

A spokesperson for the University of Oxford said a press briefing would be held once the detailed results of the interim trial were peer reviewed and published in a scientific journal.

“This will be a good time to discuss the intricate intricacies of the global trial design,” he said.

OXFORD SCIENTIST: “ IT IS NOT TRUE ”

More than 20 countries, including many poorer countries, have ordered the vaccine, which costs less than some competing vaccines and is easier to distribute.

Data from the trial was released on November 23, when developers hailed “a vaccine for the world.” Hours later, Mene Pangalos, head of non-oncology research and development at AstraZeneca, told Reuters that the half-dose schedule was a case of wrong dosing given to some volunteers.

It came to light, he said, after side effects in some participants were surprisingly mild.

“The reason we got the half dose is a fluke,” he says.

However, Professor Adrian Hill, director of the Jenner Institute at the University of Oxford, which co-developed COVID-19 with AstraZeneca and led trials in the UK, told Reuters in a telephone interview on Monday. that it was a conscious decision by the researchers to administer a lower dose.

“There had been some confusion suggesting that we didn’t know we were giving half a dose when we gave it – that’s really not true,” he said.

“What we knew was that we were using a different lot of a vaccine from a different manufacturer. We were aware of the measures in this regard and had had discussions with regulators on how to move forward.

“The dosage that we started with this new batch was half a dosage compared to what we had used previously,” he added, without giving details on the different manufacturers.

Scientists from AstraZeneca and the University of Oxford said they had consulted with health regulators and had been given the green light to continue with the half-dose among a limited group of volunteers in Britain, and to follow up with the full-dose booster at the scheduled time. .

The UK Medicines and Health Products Regulatory Agency (MHRA) has said its continued review of the vaccine is ongoing and any vaccine must undergo robust clinical trials according to international standards.

“No vaccine would be authorized for supply in the UK if expected standards of safety, quality and efficacy are not met,” a spokesperson said. She did not comment on when the regulator was consulted about the half-dose regimen.

The European Medicines Agency did not respond to repeated requests for comment.

“ MUST BE QUICKLY CLARIFIED ”

For Oxford vaccinologists, the confusion is a far cry from the euphoria of last week when provisional data seemed to justify nearly three decades of work.

But conflicting versions of events are the latest twist in vaccine data, which has caught the attention of scientists and investors since its publication.

“Whether or not they are correct, and whether or not they affect the validity of the data released last week, they need to be clarified quickly,” Riley of the University of Edinburgh said of the conflicting accounts.

While U.S. regulators have said a minimum 50% efficacy for a COVID-19 vaccine should be considered for approval, Moderna and Pfizer-BioNTech have set the bar high, reporting efficacy data above 90% for their injections.

Independent scientists have expressed concern that the AstraZeneca-Oxford half-dose group – with just over 2,700 participants – was too small to give a robust efficacy result.

That’s a fraction of the tens of thousands of trial participants that resulted in the high-potency data for Pfizer-BioNTech and Moderna vaccines.

“All we have to do is publish limited data,” Peter Openshaw, professor of experimental medicine at Imperial College London, said last week. “We have to wait for the full data and see how regulators see the results,” he said, adding that the American and European watchdogs “could possibly have a different opinion” of each other.

AstraZeneca has lost nearly 7 billion pounds ($ 9.35 billion) in value since the results of the interim trial amid these concerns.

He said he hopes more testing data collected over time in this group will consolidate the interim conclusions. It is also considering a new global trial based on the dosing regimen for clarity.

Oxford and AstraZeneca say they have submitted their reading to regulators around the world for marketing clearance. They say the dosing pattern is also being discussed with regulators.

The university said last Friday that it supported the idea of ​​additional and ongoing trials, but added that the interim analysis had already “shown the vaccine to be very effective in a global study of 24,000.”