A vaccine labeled in a test tube is seen in front of the AstraZeneca logo in this illustration taken on September 9, 2020.
Given Ruvic | Reuters
British health officials gave the go-ahead for AstraZeneca and Oxford Covid-19 vaccines on Wednesday, but also rejected one of their central claims: that half a dose followed by a standard dose offers more protection against infection.
The reassessment of the best dosage regimen for the vaccine was an unexpected move by Britain’s drug regulator based on its own analysis of unpublished data and raised new questions about the effectiveness of a vaccine that has not yet been approved in others countries.
Although cheaper and easier to distribute than rival vaccines, the Oxford / AstraZeneca vaccine has been plagued by uncertainties about its most effective dosage since data published last month showed that a half dose followed by a full dose had a 90% success, while two full shots were 62% effective.
Oxford researchers said the most successful outcome was an “intriguing outcome” 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, casting doubt on the robustness of the result.
Munir Pirmohamed, chairman of a British Covid-19 vaccine advisory group, validated those doubts on Wednesday, saying the 90% effectiveness rate did not remain during the analysis.
Instead, Pirmohamed said that a higher success rate may be due to a longer interval between administering the first and second doses.
“The low dose / standard dose regimen, although it has been cited as being 90% effective, is confused by the fact that the interval between the first and the second dose was quite long,” Pirmohamed said at a news conference.
“And we feel that this result may be related to that interval, and not to the dose itself,” he said.
UK vaccine coordinator Covid-19, Wei Shen Lim, said that a single dose of the Oxford / AstraZeneca vaccine was about 70% effective over 21 days until a second dose was administered.
Pirmohamed said that leaving the interval of three months instead of a month between doses could raise the success rate of the AstraZeneca / Oxford vaccine to 80%.
After British health officials released the 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 they will have taken into account 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.”
A ‘winning formula’
In the face of a record increase in infections caused by a highly contagious variant of the virus, Britain is prioritizing giving the first dose of a vaccine to as many people as possible instead of giving the second doses. Delaying the distribution of second shots would help to stretch the supply.
The British Medicines and Health Products Regulatory Agency (MHRA) recommended a 4-12 week interval between doses of the AstraZeneca / Oxford vaccine and also updated its guidelines for a second dose of the Pfizer-BioNTech injection saying it could be administered over 12 weeks instead of the 21 days originally recommended.
Hundreds of thousands of Britons have already received their first dose of the Pfizer vaccine after the United Kingdom was the first country to approve its launch, with the second dose expected this week.
Pfizer seemed cautious about the prospect of changing its second dose schedule, noting that it had not been evaluated under different dosing schedules.
“There is no data to show that protection after the first dose is maintained after 21 days,” said the newspaper, adding that the implementation of alternative schemes should be monitored closely.
“While decisions about alternative dosage regimens rest with the health authorities, Pfizer believes it is critical … to ensure that each recipient receives as much protection as possible, which means immunization with two doses of the vaccine.”
AstraZeneca’s CEO, Pascal Soriot, was quoted in the British Sunday Times newspaper as saying his company had a “winning formula” to rival the 95% efficacy rates shown by vaccines developed by Pfizer and Moderna. He said he could not say anything more pending the publication of new data.
Speaking to Sky News, Oxford vaccine developer Sarah Gilbert said there was transparency in the process.
“The MHRA said it will publish its evaluation report. There are different groups within the trial, we had different intervals between doses and different dosage levels, as you said, and that makes the analysis somewhat complicated,” she said.
“The MHRA has done its own analysis and they are very confident to license 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 Britain and the different efficacy rates cited by the MHRA, as well as its new recommendations on the timing of second doses, have prompted scientists to ask for the details that support their approval to be disclosed.
“More needs to be known because many points about these decisions remain unclear. MHRA and JCVI have promised 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 provide 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 the 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.”