The Food and Drug Administration has asked AstraZeneca for a large amount of additional data related to its Covid-19 vaccine, further delaying the company’s application for an Emergency Authorization (EUA) in the United States. This is based on a letter from the company from NBC News.
AstraZeneca sent the April 21 letter to US clinical trial investigators. In part it says, “This is a complex filing that includes data from studies outside of the United States, as well as emerging data from the global launch of the vaccine and significant additional data requests from the FDA.”
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AstraZeneca had expected to apply for an EUA in late March or early April.
Still, the company claims it intends to file within the “coming weeks”. In a statement to NBC News, an AstraZeneca spokesman noted “the sizeable size of the file,” adding that “in addition to US trial data, it will include real-world analysis and pharmacovigilance data from all previous studies – world-evidence data.”
While it’s not uncommon for federal regulators to request additional information from companies applying for emergency approval, the FDA most likely also wants any data from AstraZeneca on a rare type of blood clot called cerebral sinus thrombosis related to its use of the vaccine overseas. These clots have also been linked to the Johnson & Johnson vaccine used in the United States, resulting in an 11-day hiatus in the introduction of the vaccine. Both vaccines use the same technology called adenovirus to teach the immune system to fight the virus that causes Covid-19.
“If you experience any unusual side effects, a review committee may ask more detailed questions so that it can make a good judgment,” 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 do things right,” added Creech.
Since AstraZeneca’s vaccine has been used in Europe and Asia for several months, the company needs to collect a significant amount of data.
The vaccine is one of several approved by the World Health Organization for use in COVAX, a global initiative to deliver Covid-19 vaccines. WHO conducted its own safety review and concluded that the benefits of the vaccine outweighed the risks.
However, following the reports of the blood clots that caused several countries to stop using AstraZeneca’s vaccine and, in some cases, to stop using it altogether, the FDA’s decision carries considerable weight.
“What the US thinks of a product matters,” said John Grabenstein, former director of medical affairs for vaccines at Merck and former Department of Defense immunologist.
Dr. William Hartman, principal researcher for the AstraZeneca vaccine research facility at the University of Wisconsin, Madison, said the delays were frustrating for clinical trial teams in the US who had made “tremendous efforts” to study the vaccine.
But he supports the FDA’s additional efforts. “They look under every stone and make sure this is the safest product that can be put out of there,” said Hartman.
In May last year, the US gave AstraZeneca more than $ 1 billion 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 USA. Even if approved, the vaccine may never be used here.
“We can assume that we will not be using the anticipated AstraZeneca doses online,” said Andy Slavitt, a Covid-19 advisor to the Biden administration, during a briefing this week, adding that the US is shipping the AstraZeneca plan product that it has pre-purchased in 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 traction, researchers at Oxford University, who developed the vaccine in partnership with AstraZeneca, were the first to report that the shots triggered a significant immune response by removing both antibodies produced against the virus and T cells that search for and attack infected cells.
However, AstraZeneca soon experienced several setbacks and missteps that contributed to questions surrounding its data.
In November, the company admitted that some of the vials used in clinical trials did not have the correct vaccine concentration, which meant that some UK volunteers were given half a dose while others were given the full dose. The mistake created confusion about how to correctly interpret the efficacy results. AstraZeneca blamed a manufacturing problem for the error.
Then in March the National Institute for Allergies and Infectious Diseases issued an unusual statement on the night that AstraZeneca “may have taken in outdated information” to further the results of its US studies the company released hours earlier. The company was forced to review and republish its data after the Data and Safety Monitoring Board – a panel of independent experts that reviews vaccine safety and efficacy data in the US – said it had “concerns” about the data from AstraZeneca.
The different results weren’t that far apart – 79 percent effective versus 76 percent effective, but the differences created confusion, Grabenstein said. “What you’re trying to get out of Phase 3 trials is nice, clean data,” he said. “You want to show people how you did the math.”
Full data from US studies, such as Hartman’s in Wisconsin, have not yet been published.
“That means there isn’t enough safety data,” said a source with an in-depth knowledge of Covid-19 vaccines, and the AstraZeneca vaccine in particular. An AstraZeneca spokesman, who was asked for comment, referred to the company’s previous statement that it plans to file an EUA application in the coming weeks.
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Hartman said he was unable to see the full dataset from the U.S. studies, but added that he saw no major safety concerns among the nearly 400 people in his study of the AstraZeneca vaccine.
However, it is clear that AstraZeneca has significant problems to solve.
If the FDA denied AstraZeneca an EUA, it could have a dampening effect on the rest of the world. Even if the US doesn’t need the AstraZeneca vaccine, other countries do.
“If the FDA found it safe, effective, and a good vaccine for the American people,” Hartman said, “it would definitely improve his awareness around the world.”