British consent for the AstraZeneca vaccine raises more questions

British health officials gave the green light to the shooting of AstraZeneca and Oxford Covid-19 on Wednesday, but also rejected one of their central claims: that a half-dose followed by a standard dose offered more protection against infection.

The re-evaluation of the best dosing regimen for the vaccine was an unexpected move by the British drug regulator based on its own analysis of as yet unpublished data and raised new questions about the effectiveness of a vaccine that has not yet been released. has approved in other countries. .

Although cheaper and easier to distribute than rival shots, the Oxford / AstraZeneca vaccine has been plagued by uncertainties about its most effective dose since data released last month showed a half-dose followed by a single dose. complete it had a 90% success rate while two shots were 62% effective.

Oxford researchers said the most successful result was an “intriguing result” that deserved further testing.

A Reuters investigation, however, found that the existence of the low-dose / standard-dose arm was the result of a power calculation error by Oxford researchers, which called into question the robustness of the result.

Munir Pirmohamed, chairman of a British advisory group on Covid-19 vaccines, validated those doubts on Wednesday by saying the 90% efficacy rate was not kept under analysis.

Instead, Pirmohamed said a higher success rate may be due to a larger gap between the administration of the first and second shots.

“The low dose / standard dose regimen, although it has been cited as having 90% efficacy, is confused with the fact that the interval between the first and second dose was quite long,” he said. Pirmohamed at a press conference.

“And we believe this result may be related to this interval, rather than the dose itself,” he said.

Wei Shen Lim, president of the Covid-19 vaccine in the UK, said a single dose of Oxford / AstraZeneca vaccine was around 70% effective from 21 days until a second dose was given.

Pirmohamed said leaving the three-month gap instead of a one-month gap between doses could raise the success rate of the AstraZeneca / Oxford vaccine to 80%.

After British health officials revealed new details about the vaccine’s effectiveness, an AstraZeneca spokesman said: “It is up to regulators to authorize how the vaccine should be used.”

“Factors that will have been considered include the comparable immunogenic response after two doses with either regimen, as well as protection against serious illness (100%),” he said.

“We believe we have the best vaccination strategy approved by the MHRA.”

Faced with a record increase in infections caused by a highly contagious variant of the virus, Britain prioritises getting a first dose of vaccine to as many people as possible before giving two. Delaying the distribution of second shots would help stretch the supply.

The UK Medicines and Health Products Regulatory Agency (MHRA) recommended an interval of 4 to 12 weeks between doses of the AstraZeneca / Oxford vaccine and also updated its guidelines for a second dose of the shot. Pfizer-BioNTech, saying it could be administered within 12 weeks, instead of the originally recommended 21 days.

Hundreds of thousands of Britons have already received their first dose of the Pfizer vaccine after the UK became the first country to approve its implementation, with the second doses starting this week.

Pfizer seemed cautious at the prospect of changing the timing of its second dose, noting that it had not been evaluated in different dosing schedules.

“There is no data to show that protection after the first dose is maintained after 21 days,” he said in a statement, adding that the implementation of alternative programs should be closely monitored.

“While decisions about alternative dosing regimes are up to health authorities, Pfizer believes it is critical … to ensure each recipient has the maximum possible protection, which means vaccination with two doses of the vaccine.”

AstraZeneca CEO Pascal Soriot was quoted in the British Sunday Times as saying his company had a “winning formula” to rival the around 95% efficacy rates shown by vaccines developed by Pfizer and Modern. He said he could not say more data pending publication.

Speaking to Sky News, Oxford vaccine developer Sarah Gilbert said there had been transparency in the process.

“The MHRA has said it will publish its evaluation report. There are different groups within the trial, we have had different intervals between doses and different dose levels, as you say, and that makes the analysis a bit complicated, ”he said. dit.

“The MHRA has done its own analysis and is very confident in licensing the vaccine for emergency use.”

Oxford did not respond to a request for comment after the MHRA briefing.

Regulators in other countries have taken a more cautious approach than the UK and the different efficacy rates cited by the MHRA, as well as its new recommendations on the timing of second doses, led scientists to call for the details on which its approval was based were published.

“We need to know more because many points about these decisions are still unclear. MHRA and JCVI pledged to provide more information urgently,” said Saad Shakir, director of the Drug Safety Research Unit near Southampton. .

Jeremy Farrar, director of the Wellcome health research foundation, said a new trial may be needed to give clearer data on the best time for a second dose.

“We will also need to continue to track and improve our understanding of how long protection lasts and whether they can prevent transmission,” he said.

“This would be best achieved by a randomized trial on the timing of the second dose.”