The Covid-19 vaccine being developed by the University of Oxford and AstraZeneca appears to have moderate efficacy in preventing symptomatic illness, and may significantly reduce hospitalization from the disease, data from four clinical trials of the vaccine reveal.
The highly anticipated publication of the data, released Tuesday in The Lancet, also point to some signals that deserve further exploration — the possibility of protection after a single dose and the suggestion that at least one dosing regimen may have led to a decrease the number of asymptomatic infections.
“This warrants — it’s screaming for — more work in this area,” vaccine researcher Saad Omer, director of Yale University’s Institute of Global Health, said of the hint the vaccine may reduce asymptomatic infections. “You can’t ignore the results but you have to be judicious about moving forward.”
The Lancet paper was released on a busy day for Covid-19 vaccine news: The United Kingdom began vaccinating with Pfizer’s vaccine and the Food and Drug Administration posted Pfizer’s data online in advance of an advisory committee meeting Thursday looking at whether that vaccine should be given emergency use authorization in the United States.
“This is evolving science. You are seeing sausages being made — in front of the world’s eyes,” Omer said.
Topline data on the AstraZeneca vaccine from a Phase 3 trial were released in November. Tuesday’s results — the first Phase 3 clinical data for a Covid vaccine to be published in a scientific journal — pool data from trials of various phases and includes safety data on more than 20,000 participants.
The results confirm that two standard doses of the vaccine were 62% effective in preventing symptomatic Covid-19 disease in some trials. But when efficacy data from the trials were combined — including trials in which volunteers received a low dose followed by a standard dose of vaccine — the vaccine was deemed to be 70% efficacious.
Among only volunteers who received a low dose followed by a standard dose of vaccine, the vaccine had 90% efficacy.
It’s still not clear why efficacy in this group — which did not include anyone over the age of 55 — was so high. Some experts even wonder if it is the result of the play of chance, and not a true difference.
“I think there remain questions about whether the result in the low-dose standard dose is a real robust biological result,” said Natalie Dean, a biostatistician at the University of Florida. “Will it hold up?”
Some scientists have suggested the seemingly incongruous result may be due to the initial lower dose actually priming the immune system in a more effective way than a standard dose would — which, if true, would allow more people to be vaccinated more quickly, if the vaccine is approved for use.
Omer said the signal needs to be explored further, in consultation with regulatory agencies. “I think you cannot ignore the 90% efficacy signal from a scientific perspective,” he said, suggesting a new Phase 3 trial or even a Phase 2b trial could answer the question of whether this vaccine regimen actually works better.
Nahid Bhadelia, medical director of the special pathogens unit at Boston Medical Center, agreed.
“There’s a marginal cost of waiting, but there is a marginal cost of vaccinating people with what turns out to be a less efficacious strategy. What if low-dose, standard-dose is the way to go?” she asked.
AstraZeneca is still deliberating whether to conduct another trial to explore using this dosing regimen, Mene Pangalos, AstraZeneca’s executive vice president for biopharmaceuticals R & D, said Tuesday during a press briefing.
Some of the trials included in this pooled analysis collected weekly nasal swabs from participants to try to determine if the vaccine reduced asymptomatic infections, which would not come to light otherwise. This makes it unique among the Covid-19 vaccine trials.
The early findings suggested the low dose, full dose regimen may have reduced the number of asymptomatic cases. Reducing the number of unknowingly infected people in a population could cut back on transmission of the SARS-CoV-2 virus, which causes Covid-19. But lead author Andrew Pollard, director of the Oxford vaccine group, suggested more data are needed to see if this effect is real.
“At the moment this isn’t strong enough to make definite claims. But it does certainly suggest there is the potential for something important in there,” Pollard said.
Pangalos said AstraZeneca is submitting its data on a rolling basis to regulatory agencies in multiple countries around the world and expects that the data generated so far will be sufficient to win regulatory approval for the vaccine. The company expects, though, that the Food and Drug Administration will require AstraZeneca to complete its larger, ongoing U.S.-based trial before considering issuing an emergency use authorization for the vaccine in this country.
The Lancet publication pooled data from Phase 1/2 and Phase 2/3 in the United Kingdom, a Phase 3 trial in Brazil and a Phase 1/2 trial in South Africa.
Most of the participants in all of the trials were adults aged 18 to 55, so the evidence for efficacy in older adults is limited. The paper did not attempt to estimate vaccine efficacy in this population at all, saying more work would be done to look at the question.
But Pollard said immunogenicity data — generated by looking for antibody responses in blood samples from trial participants — suggest the vaccine may induce similar levels of protection across a variety of age groups “because there is no daylight between the levels of immune response even in the over 70s, when we compare with the younger adults.”
There were three severe adverse events reported, two of which may have been related to receipt of the vaccine. (One was in the control arm.) One person developed transverse myelitis, a rare but potentially serious neurological condition. This person, whose case was previously reported, received the vaccine.
Another person developed a high fever of over 104 Fahrenheit after receiving the first dose of vaccine. The fever quickly resolved and the individual continued in the trial. Whether that person received the vaccine or a placebo is still not known; his or her vaccine status is still blinded.
The efficacy data was based on 11,636 participants.
There were no cases of severe disease or hospitalization among people in the vaccine arms of the trials from three weeks after they receive their first dose — an intriguing finding. Among placebo recipients, there were 10 people who were hospitalized for Covid-19 after the first dose; two were classified as severe and one of those people died.
The Oxford-AstraZeneca vaccine is inexpensive to make and can be stored at refrigerator temperature — a major advantage over the messenger RNA vaccines being developed by Pfizer and Moderna, the vaccine race frontrunners. As such, much hope has been placed on this vaccine supplying many low- and middle-income countries.
The Pfizer and Moderna vaccines — both of which the FDA is now assessing for possible emergency use authorizations — showed efficacy of about 95%. But the Pfizer vaccine must be stored at -94 F, and will be shipped in specially built freezer packs that require dry ice. The Moderna vaccine must be stored and distributed at -4 F, but can, after thawing, be stored at fridge temperature for 30 days.
AstraZeneca CEO Pascal Soriot said all these vaccines will be needed — and more — to get the world out of the acute phase of the Covid-19 pandemic.
“It is really important to have several vaccines. In fact, if you added the announced capacity of Pfizer, Moderna, and ours, they still aren’t enough to vaccinate a sufficient number of people around the world,” he said. “We need all the vaccines.”