The Oxford/AstraZeneca Covid vaccine has efficacy of 90% in a small group who got a half-dose first, but only 62% in the majority, full trial data newly published in the Lancet has confirmed.
The results may create a quandary for regulatory bodies, which will have to decide on how the vaccine should be used if they approve it.
Oxford University and its partner, AstraZeneca, are seeking regulatory approval for their much-anticipated vaccine on the basis that it has 70% efficacy after pooling the results from trials in the UK and Brazil.
But it is the individual regulatory bodies in the UK, Europe and the US that will have to decide which dosing regimen is appropriate if they give it the go-ahead.
“Our job as scientists is to generate the data and make that publicly available for people to scrutinise and scientists to scrutinise and also now for the regulators and policymakers to scrutinise. These decisions are not for us to make,” said Prof Andrew Pollard of Oxford University, chief investigator on the trials.
It is possible the Medicines and Healthcare Products Regulatory Authority (MHRA) in the UK, the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in the US will come to different conclusions.
Prof Sarah Gilbert of Oxford University’s Jenner Institute, who led the research, told the Guardian that people in both dose groups were protected in the trials from severe illness after just one jab.
“I have no qualms about using the high dose/high dose regimen, which is what the majority of people in the trial have had,” she said.
“It’s really important to note that within 21 days of the first vaccination, nobody was admitted to hospital with Covid or had severe Covid and that’s just after one dose – that’s after any one dose in these trials – no admissions to hospital, and that’s a really major result for public health benefits.”
Both the Pfizer/BioNTech and the Moderna vaccines have reported 95% efficacy in their trials, but Gilbert said it was important to see how well the vaccines did after six months or a year. “It’s great to see high level of efficacy but that’s not the final answer on any of the vaccines really because it’s something that we need to accumulate data on over time,” she said.
There is no evidence yet on the durability of protection from the other two vaccines, both made with novel mRNA technology, whereas Oxford used an adenovirus vector – a technology that has been shown to provoke a long-term response, she said. “We shouldn’t get too hung up on comparing these early numbers.”
The FDA is unlikely to approve the vaccine as quickly as the UK and Europe. It has also expressed concerns about the limited ethnicity data in the trials and the absence of older people at highest risk, as most participants were under 55. A large trial in which 20% are older people and there is greater ethnic representation is being conducted in the US.
“We will be submitting the data to the FDA, but our best assumption is that we will need the study readout from the US before we are likely to get approval in the US,” said Mene Pangalos, executive vice-president of biopharmaceuticals R&D at AstraZeneca.
Oxford AstraZeneca’s is seen as the most globally important vaccine because it is easy to manufacture and distribute at fridge temperature, and the cost is low. AstraZeneca has undertaken to manufacture 3bn doses and is part of Covax, the UN programme to distribute vaccines to all countries in the world.
Speaking as the first people in the UK were given the first vaccine to be approved, that of Pfizer/BioNTech, the chief executive officer of AstraZeneca, Pascal Soriot, said it was important to have several versions. “In fact, if you add the capacity, at least the announced capacity, of Pfizer, Moderna and ours, there is still not enough to vaccinate sufficient number of people around the world,” said Soriot.
“We need all vaccines. So that’s really an important point to keep in mind when people start comparing data across various studies. We need all this capacity, we need all these vaccines, to help dealing with the pandemic as quickly as we can.”
The AstraZeneca vaccine is expected to be the mainstay of the UK vaccination programme. The UK has ordered 100m doses; 4m are already in the country.
The researchers say they agreed with the regulator in advance to pool the results from the different dosing trials after one small sub-group was inadvertently given a low starting dose. The expectation had been that two full doses would work best.
The efficacy data is based on 11,636 volunteers across the UK and Brazil. There were just 2,741 people in the sub-group who received a low first dose, half of whom received the vaccine and half a placebo. But efficacy in that group was 90% compared with 62% among the rest.
But the researchers say it makes sense to pool the results. “There is sufficient consistency to justify the proposal for pooled analysis of data, which will provide greater precision for both efficacy and safety outcomes than can be achieved in individual studies and provides a broader understanding of the use of the vaccine in different populations,” they write.