AstraZeneca Covid Vaccine Trial Resume In 5 Countries, But Not US

Some pharmaceutical experts think the US delay is unwarranted and risks the US falling behind vaccine development.  

But others, citing the heightened risk of political interference in the US, believe the caution is prudent. JL

Jeremy Kahn reports in Fortune:

Japan became the latest country to resume human trials of the AstraZeneca vaccine,. Trials have also resumed in the U.K., Brazil, India, and South Africa. The ongoing delay in the U.S. trial is due to the U.S. Food and Drug Administration expanding its review of safety data to include evidence from other vaccine trials that used the same underlying technology. Some experts question whether American regulators’ caution is jeopardizing the country’s ability to access one of the most promising vaccine candidates.

Trials of a leading COVID-19 vaccine candidate being produced by the drug company AstraZeneca remain on hold in the U.S. But human testing of the vaccine has resumed in at least five other countries, leading some experts to question whether American regulators’ caution is jeopardizing the country’s ability to access one of the most promising vaccine candidates.

Japan became the latest country to resume human trials of the AstraZeneca vaccine, the company said Friday. Trials have also resumed in the U.K., Brazil, India, and South Africa.

On Thursday, the European Medicines Agency, the European Union’s drug regulator, announced it had begun what’s known as a “rolling review” of AstraZeneca’s COVID-19 vaccine. This means the regulator will begin scrutinizing data from the vaccine’s trials even before those studies are concluded and a formal application for approval is submitted. The process will allow the agency to speed up its potential approval of the vaccine.

The ongoing delay in the U.S. trial is due to the U.S. Food and Drug Administration expanding its review of safety data to include evidence from other vaccine trials that used the same underlying technology, according to a Reuters report.

“We are continuing to work with the FDA to facilitate review of the information needed to make a decision regarding resumption of the U.S. trial,” AstraZeneca said in a statement.

A spokesman for the University of Oxford, whose researchers developed the vaccine AstraZeneca is producing, said it was “continuing to provide all the data requested by the FDA to AstraZeneca, who are working with the FDA to resume the U.S. arm of the [vaccine] trial.” It said that this data included information about the technology underlying the vaccine and its safety in previous vaccine trials, as well as the current COVID-19 vaccine testing.

Trials of the AstraZeneca vaccine were halted worldwide on Sept. 6 after one volunteer in the U.K. developed a serious medical condition. It has been reported that the volunteer, a woman, had developed serious neurological symptoms that might have been associated with transverse myelitis, an inflammation of the spinal cord that can be caused by an immune response.

AstraZeneca CEO Pascal Soriot also revealed that the U.K. trials had been paused once before, in July, when a different female volunteer also developed serious neurological symptoms. It was later found that she had undiagnosed multiple sclerosis.

In both cases, an institutional review board of independent experts concluded that the COVID-19 vaccine was unlikely to be the cause of the symptoms. The U.K. medical regulator allowed the British vaccine trials to resume on Sept. 13, a decision that was soon followed by most other countries where the AstraZeneca vaccine is being tested.

“We work in a regulated environment to ensure safety of our volunteers and comply with all regulatory requests and requirements,” Andrew Pollard, a researcher at Oxford’s Jenner Institute, which developed the COVID-19 vaccine and is overseeing its testing outside the U.S., said in a statement.

Genetically modified virus

AstraZeneca’s method for creating the COVID-19 vaccine rests on using a different kind of virus, called an adenovirus. This virus has been genetically modified so that it does not replicate and so that when it infects cells, it instructs them to make a protein that is also found on the surface of the coronavirus that causes COVID-19. This protein then hopefully prompts an immune response that enables those inoculated to fight off a COVID-19 infection. In the case of the AstraZeneca vaccine, the kind of adenovirus being used is one normally found in chimpanzees.

Researchers at Oxford’s Jenner Institute have used this particular chimpanzee adenovirus in a number of other vaccines, including ones designed to protect against Ebola and Middle East respiratory syndrome (MERS). Other researchers have used different strains of chimpanzee adenovirus in other vaccine studies too.

“There has been multiple trials for chimpanzee adenovirus vector, and I am not aware of a single serious adverse event in any of these trials,” Hildegund Ertl, a professor in the vaccine and immunotherapy center at the Wistar Institute in Philadelphia, said.

Alan Parker, a professor of translational virotherapies at Cardiff University in the U.K., also said the chimpanzee adenovirus was a safe vaccine technology. “It has been fairly extensively trialed,” he said. “The number of adverse events have been minimal.”

He said that given the number of people involved in the Phase III trial of the Oxford-AstraZeneca vaccine in the U.K.—up to 10,000 volunteers are being recruited—it was to be expected that the study would uncover a few individuals with undiagnosed pre-existing health issues that have no bearing on the vaccine’s safety. “My personal view is that the few serious adverse events found so far are likely just noise,” he said.

Ertl said the FDA was being overly cautious in holding up the U.S. trial of the AstraZeneca vaccine while reviewing safety data from earlier studies. But she said she could understand why the U.S. regulator might be more wary of it than its counterparts in Europe owing to varying degrees of anti-vaccine sentiment as well as the litigiousness of the U.S.

“The FDA has to be more careful,” she said.

Vaccine skeptics

Six in 10 Americans said they would not rush to get a COVID-19 vaccine as soon as one was approved by the FDA, according to an Axios/Ipsos poll released last month. That compares with three out of four who said they would get a vaccine once one is available globally, according to another Ipsos poll released in August.

But the growing divide between the FDA and other global regulators may mean the U.S. won’t be in a position to approve the AstraZeneca vaccine as soon as other countries. The large 30,000-person clinical trial of the vaccine that AstraZeneca is conducting in the U.S. had only been underway for about a week when the trials were paused. And while Soriot initially said the delay would not set back the company’s projections of having a vaccine ready for FDA approval before the end of the year, that timeline is now in doubt.

It is unclear if the FDA will approve a COVID-19 vaccine based entirely on trial data from outside the U.S.

Meanwhile, two of AstraZeneca’s leading rivals in the race to be the first to bring a COVID-19 vaccine to market—drug giant Pfizer and biotechnology company Moderna—have large-scale U.S. clinical trials well underway. Pfizer has said that it should have enough data from its study to ask the regulator for approval by the end of this month.

The U.S. government has provided AstraZeneca with $1.2 billion to help fund development of its vaccine. In exchange, the company has promised the country 300 million doses, with the first doses ready to ship as early as this month. AstraZeneca said it would still be able to deliver those doses even if the U.S. takes longer than other countries to approve the vaccine.