AstraZeneca said Monday that its coronavirus vaccine reduced the risk of symptomatic Covid-19 by an average of 70.4%, according to an interim analysis of large Phase 3 trials conducted in the United Kingdom and Brazil.
The results, while positive, suggest the vaccine may be less effective than two others. Earlier this month, Moderna and the Pfizer and BioNTech consortium announced their messenger RNA, or mRNA, vaccines showed 95% efficacy against Covid-19 infections in their respective clinical trials.
Still, researchers at the University of Oxford, which partnered with AstraZeneca to develop the vaccine, hailed the latest data as promising.
“The announcement today takes us another step closer to the time when we can use vaccines to bring an end to the devastation caused by SARS-CoV-2,” Sarah Gilbert, one of the co-developers of the vaccine, said in a statement.
The preliminary results on the AstraZeneca vaccine were based on a total of 131 Covid-19 cases in a study involving 11,363 participants. The findings were perplexing. Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. That latter analysis was conducted on a small subset of the study participants, only 2,741.
A U.S.-based trial, being supported by Operation Warp Speed, is testing the two-full-dose regimen. That may soon change. AstraZeneca plans to explore adding the half dose-full dose regimen to its ongoing clinical trials in discussions with regulatory agencies, a spokesman told STAT in an email.
“We see a lot of merit in this regimen and we will now start discussions with regulators into incorporating this dose combination for further clinical investigation,’’ Brendan McEvoy said.
Why would less vaccine produce a better result?
“That’s a good question,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told STAT. Fauci suggested “there’s going to be a lot of hand waving” as people try to explain the results.
Fauci said it was possible the approach overrides a concern that exists about using two doses of a viral-vectored vaccine — the type AstraZeneca is developing. It uses an adenovirus that has been modified to include genetic material from the SARS-CoV-2 virus so that it introduces the immune system to the spike protein, which sits on the exterior of the virus.
Some experts had feared that if viral-vectored vaccines required a priming and then a boosting dose, the immune system might recognize the viral vector — in this case the adenovirus — and shut down the immune response before the vaccine has a chance to boost the response to the spike protein.
Fauci said the smaller initial dose may “tickle” the immune system enough to generate T cells, but not trigger development of antibodies that might work to suppress the response to the booster shot.
If a final analysis, conducted after the inclusion of additional data, concludes the vaccine’s actual efficacy is around 70%, that could be a problem.
“If it’s 70%, then we’ve got a dilemma,” said Fauci. “Because what are you going to do with the 70% when you’ve got two [vaccines] that are 95%? Who are you going to give a vaccine like that to?”
The problem was also flagged in an analysis by Geoffrey Porges of the investment bank Leerink. “We believe that this product will never be licensed in the US,” Porges wrote.
Fauci cautioned that full datasets — which the Oxford researchers said they intend to publish in a scientific journal — need to be pored over before conclusions can be drawn.
“We’ve got to look at the analyses, the real granular data. It’s always tough when you’re looking at a press release to figure out what’s going on,” Fauci said.
Other experts were more enthusiastic about the findings, suggesting the vaccine could be an important tool in low- and middle-income countries, where substantial production of the vaccine is expected to take place.
“The top line is this is more great news,” said Dave O’Connor, a vaccinologist at the University of Wisconsin-Madison, who is a volunteer in the AstraZeneca trial. (He believes he received the placebo, because he had no side effects after either dose.)
Beth Kirkpatrick, chair of the department of microbiology and molecular genetics at the University of Vermont, also saw good news.
“The AstraZeneca preliminary efficacy data are strong, but somewhat hard to compare to other vaccines due to variability in study design,” she said in an email. “Importantly, thus far, no volunteer who received this vaccine experienced severe Covid disease. This is great news, as is the initial suggestion that this vaccine might decrease asymptomatic infection.”
The Oxford researchers suggested the vaccine may reduce transmission of the virus, because they saw fewer asymptomatic cases in their trial. One of the challenges of controlling spread of the SARS-CoV-2 virus is that some people who become infected have no symptoms but can still transmit the virus.
There were no hospitalized or severe cases of Covid-19 reported in the studies. No serious safety events related to the vaccine occurred in the studies, AstraZeneca said.
Results from the U.S. trial will be delayed because that trial was paused for more than a month after one of the participants in the U.K. trial developed a rare but neurological condition, described as consistent with transverse myelitis. The Food and Drug Administration allowed the trial to resume in late October.
AstraZeneca said in a release that it intends to seek emergency use authorizations in countries around the world that have a regulatory framework that allows for conditional or early approval of medical products, and will seek an emergency use listing from the World Health Organization, a pathway to rapid approval for low-income countries.
The vaccine can be stored at normal refrigeration temperatures for up to six months, which will make it easier to deploy in more settings than the vaccines from Pfizer and Moderna, which must be stored at ultra-low temperatures. The Pfizer vaccine must be stored at -94 degrees Fahrenheit, while the Moderna must be stored at -4 F. Once thawed, Moderna’s vaccine can be stored at fridge temperature for a month.
“The vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available,” AstraZeneca CEO Pascal Soriot said in a statement.
AstraZeneca said it is on track to be able to produce 3 billion doses of its vaccine in 2021.