LONDON – Positive interim data from the U.S. trial of Astrazeneca plc’s COVID-19 vaccine have added yet more evidence it is effective in older adults and quelled concerns about serious thrombotic events that led countries in Europe to pause use of the vaccine earlier this month.

Overall, the vaccine showed 79% efficacy in preventing symptomatic COVID-19, and was 100% effective in preventing serious disease and hospitalization.

The effect was comparable across different ethnicities and age groups, with 80% efficacy in participants over 65 years of age. The analysis is based on 141 cases of COVID-19 infection.

In the face of post rollout reports in Europe of thrombotic events, including a few cases of cerebral venous sinus thrombosis (CVST), the data safety monitoring board conducted a specific review with the help of an independent neurologist.

That concluded there was no increase in risk among 21,583 participants who had received at least one dose of the vaccine in the 32,000-strong trial. A specific search for CVST found no occurrence in the study.

The results add to the previous body of evidence that shows the vaccine is well-tolerated and highly effective against COVID-19 infections of differing severity and across all age groups, according to Mene Pangalos, executive vice president of biopharmaceuticals at Cambridge-based Astrazeneca. “We are preparing to submit these findings to FDA and for the rollout of millions of doses across America, should the vaccine be granted U.S. emergency use authorization,” he said.

Assuming approval, Ruud Dobber, president of Astrazeneca’s U.S. biopharmaceuticals business unit, said the company is ready to deliver 30 million doses immediately, with a further 20 million doses available within the first month, to be followed by 15 million to 20 million doses per month after that.

In the view of Andrew Garrett, executive vice president of scientific operations at the contract research organization ICON Clinical Research, interpretation of the study is more straightforward than earlier trials sponsored by Oxford University. “This is clearly stated as an Astrazeneca-led trial, and it more closely follows the large phase III vaccines trials reported by other sponsors,” Garrett said, commenting on the results.

“Importantly, the trial provides further support for efficacy in the elderly, where previous clinical trial data, other than immunological data, had been lacking,” Garrett said.

Approximately 20% of participants were over 65, and of those, 60% had co-morbidities that are likely to result in more severe COVID-19, including diabetes, cardiovascular disease and severe obesity.

The study randomized participants 2-to-1 to vaccine or placebo, providing a large safety database in which to investigate the potential association of the vaccine with thrombotic events and specifically CVST, Garrett noted. “It was reported there was no increased risk of thrombosis. These data are therefore timely in further addressing any safety concerns that could undermine vaccine uptake,” he said.

In addition to the U.S., participants were recruited in Chile and Peru, adding to previous trial data from the U.K., Brazil and South Africa, and to real-world effectiveness data from the U.K., where more than 10 million doses of the Astrazeneca vaccine have been administered.

Andrew Pollard, professor of pediatric infection and immunity, who was lead investigator for the Oxford University trials of the vaccine, including the phase III study, said the absolute efficacy is higher in this new study than observed in the Oxford-led studies because efficacy is affected by the protocol case definition, which was higher for more severe cases, and also reflects the population in which the study was conducted. “Today’s findings are in line with findings from other major vaccine developers who studied efficacy in the U.S.,” Pollard said.

The results “show the remarkable efficacy of the vaccine in a new population and are consistent with the results from Oxford-led trials,” said Pollard.

The U.S trial used a dosing interval of four weeks, but Astrazeneca’s Pangalos said the weight of evidence suggests there will be increased efficacy if the interval is longer. Timing in the U.S. study was “very tight,” with doses administered four to five weeks apart. “The reason we are stating three months is optimal is because of the U.K., South Africa and Brazil data,” said Pangalos. “That science is holding.” All the data on dosing intervals and efficacy will be submitted for the FDA to decide what the schedule should be, he said.

Global supply network

The data give reason to believe the Astrazeneca vaccine is effective against SARS-CoV-2 variants of concern that are threatening to undermine vaccines directed at the spike protein of the virus, Pangalos claimed. “Given [the trial] is much later in terms of timing, it’s very encouraging we got such high efficacy, given the variants are out there,” he said.

The prevalence of different variants circulating during the study is not clear as yet, but is under active investigation and there will be an analysis of all variants encountered in the trial.

Astrazeneca now has conditional or emergency use approval in more than 70 countries and the World Health Organization also has granted emergency use listing, opening up the path to access in 142 countries in line to be supplied by the COVAX global facility, that is aiming to ensure equitable access.

However, Astrazeneca has found itself at the center of a diplomatic row in Europe over supplies of the vaccine, and the EU has threatened to introduce export controls. Dobber said the company has built a global supply network involving 20 partners and it needs free movement of all the various components to deliver doses to contract. “It’s incredibly important our goods can move from one country to another,” he said, noting EU vaccine supplies rely on drug substance produced in the U.S.

There is no squeeze on any supplies or components needed to deliver the U.S. orders; however, Astrazeneca is trying to increase yields of the bioprocesses, Pangalos said.

Astrazeneca received the phase III U.S. data over the weekend and discussed it with the U.S. government on Sunday morning (March 21). “They are very excited about the dataset,” Dobber said, adding he would be “personally highly surprised” if all the expected deliveries are not used in the U.S. “All doses belong to the U.S. government,” he said, and “there is still significant unmet need.”

Under a contract the Biomedical Advanced Research and Development Authority signed in May 2020, Astrazeneca received $1 billion for the clinical development, manufacturing and delivery of the vaccine, as part of Operation Warp Speed. The phase III U.S. trial was part of this agreement.