The Food and Drug Administration has asked AstraZeneca for a large amount of extra data related to its Covid-19 vaccine, which further delays the company’s application for an emergency use authorization or EUA in the US, according to a letter from the company obtained. by NBC News.
AstraZeneca sent the letter dated April 21 to U.S. clinical trial investigators. It reads in part “This is a complex submission that includes data from studies conducted outside the United States as well as new data from the global rollout of the vaccine, and significant additional requests for data from the FDA have been received.”
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AstraZeneca had expected to file an EUA in late March or early April.
Still, the company maintains that it intends to file within “the coming weeks.” In a statement to NBC News, a spokesman for AstraZeneca noted the “large size of the file” and added that “in addition to the US trial data, the archive will also include analyzes and drug monitoring from all studies to date, in addition to real-world real-world data.”
While it is not uncommon for federal regulators to request additional information from companies seeking authorization for emergency use, the FDA is also likely to see all of AstraZeneca’s data on a rare type of blood clot called cerebral sinus venous thrombosis associated with the vaccine’s use abroad. These blood clots have also been linked to the Johnson & Johnson vaccine in use in the United States, leading to an 11-day break in vaccine rollout. Both vaccines use the same technology, called an adenovirus, to teach the immune system to fight the virus that causes Covid-19.
“When there are unusual side effects that occur, there may be even greater details that an assessment committee will ask for so that they can give a good assessment,” said Dr. Buddy Creech, Director of the Vanderbilt Vaccine Research Program at Vanderbilt University Medical Center in Nashville.
“The FDA is under a lot of pressure to get things right,” Creech added.
As AstraZeneca’s vaccine has been in use for several months throughout Europe and Asia, there is a significant amount of data that the company needs to collect.
The vaccine is one of several approved by the World Health Organization for use in COVAX, a global initiative working to deliver Covid-19 vaccines. The WHO conducted its own safety review and concluded that the benefits of the vaccine outweigh any risks.
But after reports of blood clots – which led several countries to stop using AstraZeneca’s vaccine, and in some cases to stop it altogether – the FDA’s decision has significant weight.
“What the United States thinks of a product matters,” said John Grabenstein, former chief medical officer for vaccines at Merck and a former immunologist at the Department of Defense.
Dr. William Hartman, lead researcher for the AstraZeneca vaccine test site at the University of Wisconsin, Madison, said the delays are frustrating for clinical trial teams in the United States that “made a huge effort” to test the vaccine.
But he supports the FDA’s extra efforts. “They look under every rock and make sure this is the safest product that can be placed out there,” Hartman said.
Last May, the United States donated more than $ 1 billion to AstraZeneca to develop and study its Covid-19 vaccine as part of the Trump administration’s vaccine initiative, Operation Warp Speed. Due to this agreement, AstraZeneca is contractually obliged to apply for an EUA in the United States. Even if approved, the vaccine can never end up being used here.
“We can predict that we will not use the AstraZeneca doses that we expect to come online,” Andy Slavitt, a Covid-19 adviser to the Biden administration, said during a briefing this week, adding that the United States is planning to ship AstraZeneca product, it pre-purchased to other countries in need.
“We have an adequate supply of vaccines,” said Slavitt, referring to the doses from Pfizer-BioNTech, Moderna and Johnson & Johnson.
Setbacks and missteps
Last summer, as the race to develop a Covid-19 vaccine gained momentum, Oxford University researchers developing the vaccine in partnership with AstraZeneca were the first to report that the shots led to a significant immune response by producing both antibodies against the virus and T cells that search for infected cells and attack them.
But AstraZeneca soon experienced several setbacks and missteps that contributed to questions about its data.
In November, the company acknowledged that some of the vials used in clinical trials did not have the correct concentration of vaccine, meaning some volunteers in the UK received half a dose while others received the full dose. The error led to confusion as to the correct way to interpret the results of efficiency. AstraZeneca blamed the error on a manufacturing problem.
Then, in March, the National Institute of Allergy and Infectious Diseases issued an unusual late-night statement saying AstraZeneca “may have included outdated information” to encourage the results of its U.S. trials, which the company had released just hours before. The company was forced to review and publish its data after the Data and Safety Monitoring Board – a panel of independent experts reviewing safety and efficacy data for vaccines in the US – said it had a “concern” about AstraZeneca’s data.
The different results were not that far apart – 79 percent effective versus 76 percent effective, but the differences led to confusion, Grabenstein said. “What you want out of Phase 3 trials is neat, clean data,” he said. “You want to show people how you did the math.”
Full data from the U.S. trials that the Hartman ran in Wisconsin have not yet been released.
“This implies that there is an insufficient amount of safety data,” said a source with in-depth knowledge of Covid-19 vaccines and in particular the AstraZeneca vaccine. Asked for comment, an AstraZeneca spokesman referred to the company’s previous statement that it plans to file an EUA in the coming weeks.
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Hartman said he has not been able to see the entire dataset from the U.S. trials, but added that he did not see any major safety issues among the nearly 400 people in his study of the AstraZeneca vaccine.
It is still clear that AstraZeneca has significant problems to solve.
If the FDA denies AstraZeneca an EUA, it could have a dampening effect on the rest of the world. Although the United States does not need the AstraZeneca vaccine, other countries do.
“If the FDA finds it safe and effective, and a good vaccine is to be used in the American people,” Hartman said, “it would definitely help its perception worldwide.”
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