In news that should be reassuring for skeptics, the Oxford/AstraZeneca COVID-19 vaccine was found to be 79% effective in preventing symptomatic COVID-19 and 100% effective against severe disease and hospitalization in results of a late-stage clinical trial, published today by the pharma company.

What’s more, analysis of safety results by an independent board found no increased risk of blood-clotting (thrombosis) among the trial participants, the company said in it’s statement – reinforcing findings of the European Medicines Agency (EMA) last week that the vaccine is safe – despite some rare blood clotting events seen in Europe, particularly among young women, that warrant further investigation.

Among trial participants over the age of 65, the vaccine efficacy rate reached 80%. This news is also reassuring, given the limited data on the vaccine efficacy in older individuals that had been seen to date, and which had led many EU countries to set age restrictions on the AstraZeneca vaccine in the first phases of rollout. 

The results of the large-scale trial, with many participants in the United States, also are expected to pave the way for approval of the vaccine by the United States Food and Drug Administration (FDA).

New AZ Trial Results – United States, Peru & Chile

The new trial was conducted in the US, Peru and Chile, with 32,449 participants. Efficacy was consistent across age and ethnicity, although 79% of the participants were white, 22% were hispanic, and only 8% were black, 4% asian, and 4% native American. 

In the initial set of Phase 3 trials, which had taken place largely in the United Kingdom and Brazil, only 12% of participants were older than 55. In contrast, the newly reported US trial arm had one fifth of the participants over 65 and approximately 60% had co-morbidities – which would normally increase their risk of developing severe illness, including diabetes, severe obesity, and cardiac disease.

“These findings reconfirm previous results observed in AZD1222 trials across all adult populations, but it’s exciting to see similar efficacy results in people over 65 for the first time,” said Ann Falsey, co-lead Principal Investigator for the US trial, in a press release issued by the pharma company. 

“This analysis validates the AstraZeneca COVID-19 vaccine as a much-needed additional vaccination option, offering confidence that adults of all ages can benefit from protection against the virus,” she added. 

AstraZeneca said that it now plans to submit these findings to the FDA in the coming weeks to receive emergency use authorization. The primary analysis of the data, once it is completed, will also be submitted for peer-reviewed publication.

Planned Delivery of Doses

Meanwhile, AstraZeneca announced on Monday in a press conference that it would deliver 30 million doses of the vaccine to the United States in the first half of April after receiving approval and another 20 million later on in the same month. Subsequently, 15 to 20 million doses will be delivered. 

US health officials have predicted that the country will have enough doses to vaccinate every adult by May using the three vaccines currently approved – Pfizer/BioNTech, Moderna, and Johnson & Johnson.

It is unclear how big of a role the AstraZeneca vaccine will play in the US’ vaccination campaign and whether the government will donate excess doses to countries lacking in vaccines.

At a press conference on Monday, Ruud Dobber, President of AstraZeneca’s Biopharmaceuticals Business Unit, said he would be “very surprised” if the doses were not used to vaccinate Americans. 

Blood Clots and Vaccine Hesitancy

In addition to the trial results, an independent data safety monitoring board (DSMB) conducted a specific review of thrombotic events, including cerebral venous sinus thrombosis (CVST) – a rare disorder of clots in vessels draining from the brain – seen in association with the vaccine’s administration in a number of cases in Europe.

The board found no increased risk of thrombosis among the trial participants, echoing the message from the EMA last week, which stated that the vaccine is safe and effective. 

“We hope this will lead to even more widespread use of the vaccine in the global attempts to bring the pandemic to an end,” said Sarah Gilbert, Professor of vaccinology at Oxford University and co-designer of the vaccine.

According to the latest EMA data, of an estimated 20 million people in the United Kingdom and Europe that had received the vaccine as of March 16, the EMA had identified 18 cases of CVST (cerebral events), occurring shortly after vaccine administration, as well as seven other cases of disseminated intravascular coagulation, DIC.

Although no causal connection has been found between the vaccine and the blood clotting, and several countries have now resumed the rollout of the vaccine, trust in AstraZeneca’s vaccine has taken a hit, particularly in Spain, Germany, France and Italy. 

In a poll conducted by YouGov in March, which included 8,000 participants in seven European countries, respondents were more likely to view the AstraZeneca vaccine as unsafe than safe. 

Some 61% of French, 55% of Germans, 52% of Spaniards, and 43% of Italians said it was unsafe. Confidence in the vaccine has fallen since a poll conducted in February.

“After concerns about its protection and potency were raised by leaders across Europe, the Oxford/AstraZeneca vaccine has undoubtedly suffered damage to its reputation for safety on the Continent,” said Matt Smith, lead data journalist at YouGov, in a statement.

“Not only have we seen considerable rises in those who consider it unsafe in the last two weeks in Europe, the AstraZeneca vaccine continues to be seen as substantially less safe than its Pfizer and Moderna counterparts,” Smith added.

The same decline in public confidence was not seen in the UK, where 77% of participants considered the jab safe. 

According to William Schaffner, Professor of Medicine in Infectious Diseases at the Vanderbilt University School of Medicine, “there will be spillover to the United States, where…there is a substantial group of vaccine hesitant and skeptical people whom we have yet to win over. And all of this discussion, I’m sure, gives them further pause,” he said in an interview with CNBC.

The vaccine has been granted authorization in over 70 countries and received Emergency Use Listing from WHO, leading the way for its use in the COVAX facility to supply low- and middle-income countries with vaccines. 

Serum Institute of India Announces Delays in Supply of AZ Vaccine to several countries.

In other AstraZeneca vaccine news, the Serum Institute of India, a pharma company producing the Oxford/AstraZeneca vaccine for many low-  and middle-income countries, informed Brazil, Morocco and Saudi Arabia that there will be a delay in delivering vaccines they ordered due to a fire in one of the production buildings.

This has “caused obstacles to the expansion of our monthly manufacturing output,” said the Serum Institute in a statement delivered to the Fiocruz Institute in Brazil. 

The statement contradicted one that was provided immediately after the fire took place in which SII said that it would have no effect on vaccine production.

On a brighter side, the company said a production factory in the Netherlands could soon be approved by the EMA. This would expand the doses available to the EU, which has been plagued by vaccine shortages and a slow rollout across the 27-member bloc. 

The announcement came after several months of dispute between AstraZeneca and the European Union over manufacturing hiccups and vaccine supply constraints.   

At the same time, AstraZeneca is the major vaccine supplier of the WHO co-supported COVAX initiative  – and even as production in Europe and the United States moves into higher gear, it may be expected that countries in those regions will come under increased scrutiny for holding onto precious vaccine doses – while LMICs continue to wait.    

“AstraZeneca continues to engage with governments, multilateral organizations and collaborators around the world to ensure broad and equitable access to the vaccine at no profit for the duration of the pandemic,” said AstraZeneca’s statement. 

Image Credits: gencat cat/Flickr, University of Oxford, Sophie Scott/ABC.