FDA wants 'significant' amount of additional data on AstraZeneca's Covid vaccine

FDA wants ‘significant’ amount of additional data on AstraZeneca’s Covid vaccine

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 request for an emergency use authorization, or EUA, in the United States, according to a letter from the company obtained by NBC News.

AstraZeneca sent the letter, dated April 21, to US 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 emerging data from the global vaccine deployment and significant requests for additional data. were received from the FDA. “

Comprehensive coverage of the coronavirus outbreak

AstraZeneca had planned to file an EUA application in late March or early April.

Still, the company maintains that it intends to file in “the next few weeks.” In a statement to NBC News, a spokesperson for AstraZeneca noted “the substantial size of the case”, adding that “in addition to the data from trials in the United States, the filing will also include the analyzes and pharmacovigilance of all studies to date, in addition to actual data – global evidence data. “

While it is not unusual for federal regulators to request additional information from companies seeking emergency use authorization, the FDA probably also wants to see all of AstraZeneca’s data on a rare type of blood clot. called venous thrombosis of the cerebral sinus due to the use of the vaccine abroad. These clots were also linked to the Johnson & Johnson vaccine used in the United States, resulting in an 11-day break in vaccine deployment. Both vaccines use the same technology, called adenoviruses, to teach the immune system to fight off the virus that causes Covid-19.

“When there are unusual side effects that occur, a review committee may ask for even more details so that they 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,” Creech added.

Since AstraZeneca’s vaccine has been in use for several months in Europe and Asia, the company has to collect a significant amount of data.

The vaccine is one of several vaccines authorized by the World Health Organization for use within COVAX, a global initiative to provide Covid-19 vaccines. WHO conducted its own safety review and concluded that the benefits of the vaccine outweighed all the risks.

But following reports of the blood clots – which led several countries to suspend use of AstraZeneca’s vaccine and, in some cases, stop its use altogether – the FDA’s decision carries considerable weight.

“What the United States thinks of a product matters,” John Grabenstein, former executive director of vaccine medical affairs at Merck and former Department of Defense immunologist.

Dr William Hartman, principal investigator for the AstraZeneca vaccine trial site at the University of Wisconsin, Madison, said the delays are frustrating for clinical trial teams in the United States who “are putting in tremendous effort. To study the vaccine.

But it supports the additional efforts of the FDA. “They look under every stone, making sure it’s the safest product that can be put on the market,” Hartman said.

Last May, the United States gave AstraZeneca more than $ 1 billion to develop and study its Covid-19 vaccine as part of the Trump administration’s vaccination initiative, Operation Warp Speed. As a result of this agreement, AstraZeneca is contractually obligated to request an EUA from the United States. But even if it is licensed, the vaccine may never be used here.

“We can predict that we will not be using the doses of AstraZeneca that we plan to put online,” Andy Slavitt, a Covid-19 adviser in the Biden administration, said in a briefing this week, adding that the United States planned to ship the AstraZeneca. product he has pre-purchased in other countries in need.

“We have an adequate supply of vaccines,” Slavitt said, referring to doses from Pfizer-BioNTech, Moderna and Johnson & Johnson.

Retreat and misstep

Last summer, as the race to develop a Covid-19 vaccine gathered momentum, researchers at the University of Oxford, who developed the vaccine in partnership with AstraZeneca, were the first to report that injections elicited a significant immune response by producing both antibodies against the virus. and T cells, which seek out infected cells and attack them.

But AstraZeneca quickly experienced several setbacks and missteps that helped question 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 were given half a dose, while others were given the full dose. The error led to confusion as to the correct way to interpret the efficacy results. AstraZeneca attributed the error to a manufacturing problem.

Then in March, the National Institute of Allergy and Infectious Diseases issued an unusual statement late at night saying AstraZeneca “may have included outdated information” in the encouraging results of its US trials that the company had released a few times. hours earlier. The company was forced to review and republish its data after the Data and Safety Monitoring Board – an independent expert group that reviews vaccine safety and efficacy data in the United States – said it had a ” concern ”regarding AstraZeneca data.

The different results weren’t that far apart – 79% effective vs. 76% effective, but the differences led to confusion, Grabenstein said. “What you want from the Phase 3 trials is nice, clean data,” he said. “You want to show people how you did the math.”

Full data from trials in the United States, like the one conducted by Hartman in Wisconsin, have not yet been released.

“This implies that there is an insufficient amount of safety data,” said a source with extensive knowledge of Covid-19 vaccines and the AstraZeneca vaccine in particular. Asked for comment, a spokesperson for AstraZeneca referred to the company’s previous statement that it plans to file an EUA application in the coming weeks.

Download the NBC News app for comprehensive coverage of the coronavirus outbreak

Hartman said he had not been able to see the full data from the US trials, but added that he did not see any major safety concerns among the nearly 400 people in his study of the AstraZeneca vaccine.

Still, it’s clear that AstraZeneca has some serious issues to tackle.

If the FDA were to deny AstraZeneca an EUA, it could have a moderating effect on the rest of the world. Although the United States does not need the AstraZeneca vaccine, other countries do.

“If the FDA found it to be safe and effective, and a good vaccine for the American population to use,” Hartman said, “it would definitely help its perception around the world.”

Follow NBC HEALTH on Twitter & Facebook.