European Union Recommends Authorization of AstraZeneca’s COVID-19 Vaccine

The European Medicines Agency (EMA) has recommended granting commercial marketing authorization of the AstraZeneca COVID-19 vaccine for individuals 18 years and older.

The vaccine was formerly known as AZD1222 and is now referred to as the COVID-19 Vaccine AstraZeneca.

“Today’s recommendation underscores the value of AstraZeneca’s COVID-19 vaccine which is not only effective and well-tolerated, but also easy to administer and, importantly, protects fully against severe disease and hospitalizations,” AstraZeneca CEO Pascal Soriot, said.

Following review of the application, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its opinion on data from a rolling review of trial data from the primary analysis of the phase 3 program led by the University of Oxford.

Additional safety and efficacy data for the vaccine will continue to accumulate from ongoing clinical trials and is expected to be published in the coming weeks.

The CHMP recommends two doses of vaccine to be administered at a 4 to 12 week interval in people aged 18 years and older. This dosing regimen was shown in clinical trials to be safe and effective in preventing symptomatic COVID-19, with no severe cases and no hospitalizations more than 14 days after the second dose.

Back in December, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) announced it had provided an emergency authorization of the AstraZeneca vaccine for individuals 18 years and older.

“Today is an important day for millions of people in the UK who will get access to this new vaccine. It has been shown to be effective, well-tolerated, simple to administer and is supplied by AstraZeneca at no profit,” AstraZeneca CEO Pascal Soriot, said at that time. “We would like to thank our many colleagues at AstraZeneca, Oxford University, the UK government and the tens of thousands of clinical trial participants.”

In addition, the vaccine has been granted a CMA or emergency use in 20 countries, including a number of Latin American countries, India, and Morocco. The company has not yet filed for an emergency use authorization (EUA) with the US Food and Drug Administration (FDA).

The Vaccine

The vaccine was developed by the University of Oxford and its spin-out company, Vaccitech. It uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus, adenovirus, that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein.

After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.

Data

The primary efficacy endpoint of the program statistical plan, based on the pooling of two dosing regimens, showed that the vaccine is 70.4% (95.8% CI: 54.8% to 80.6%) effective at preventing symptomatic COVID-19 occurring more than 14 days after receiving two doses of the vaccine.

A secondary efficacy endpoint of prevention of severe disease demonstrated no cases of severe infections or hospitalizations in the vaccine group.

A further analysis of the efficacy regimens showed that when the vaccine was given as two full doses, vaccine efficacy was 62.1% (n=8,895; CI 41.0% to 75.7%), and 90.0% (n=2,741; CI 67.4% to 97.0%) in participants who received a half dose followed by a full dose.

Vaccine efficacy was also assessed on the secondary endpoint of early prevention of severe disease after the first dose. There were no hospitalizations or severe cases of COVID-19 more than 21 days after the first dose of the vaccine. Ten participants in the control group were hospitalized due to COVID-19, among whom two were assessed as severe, including one fatal case.

More data will continue to accumulate as part of the upcoming primary analysis and further follow-up, refining the efficacy reading and characterizing vaccine efficacy over a longer period of time.

The safety data published so far is from over 20,000 participants enrolled across four clinical trials in the UK (COV001 and COV002), Brazil (COV003) and South Africa (COV005).

The data was reported in The Lancet back in December.

Challenges

Questions arose shortly after the data was initially reported in late November about its efficacy. However, additional data was published in the aforementioned article in The Lancet and the MHRA’s decision was based on independent advice from its Commission on Human Medicines following a rolling review of trial data that included an interim analysis of the phase 3 trial.

“The regulator’s assessment that this is a safe and effective vaccine is a landmark moment, and an endorsement of the huge effort from a devoted international team of researchers and our dedicated trial participants. Though this is just the beginning, we will start to get ahead of the pandemic, protect health and economies when the vulnerable are vaccinated everywhere, as many as possible as soon possible,” Professor Andrew Pollard, director of the Oxford Vaccine Group and chief investigator of the Oxford Vaccine Trial, said.

Most recently, the company has been at odds with the European Union (EU) over vaccine supplies. AstraZeneca told the EU it cannot deliver the amount that was requested. As reported on CNN, AstraZeneca CEO Pascal Soriot told the Italian newspaper la Repubblica on Tuesday that AstraZeneca was not able to guarantee the timing of EU deliveries because countries such as the United Kingdom were quicker to finalize orders. There are also crucial differences in the EU and UK vaccine contracts.

"The contract with the UK was signed first and the UK, of course, said 'you supply us first,' and this is fair enough," Soriot said. Three months later, when the European Union wanted to be supplied "more or less at the same time" as the United Kingdom, AstraZeneca was not able to make that commitment.”