AstraZeneca approvals abroad fuel debate over speeding US process

Recent authorization of AstraZeneca’s COVID-19 vaccine in the United Kingdom and European Union has sparked the question: Why not here as well?

Positive data from the vaccine released Wednesday, combined with the urgent need for more doses in the U.S., is now fueling the debate.

Clinical trials in the U.K., South Africa and Brazil found that the vaccine has 76 percent efficacy after a single dose, rising to 82 percent when a second dose is given three months later.

The Food and Drug Administration (FDA), however, is waiting for completion of a U.S. clinical trial before it’s expected to make a decision.

AstraZeneca has not yet applied to the FDA for authorization, and a top company official said Wednesday it doesn’t think it can get it before the trial finishes in “the next month or two.”

“In terms of getting an approval, we do think we will need that U.S. data,” said Mene Pangalos, executive vice president at AstraZeneca, during a press briefing.

Some experts, though, say there should at least be a discussion of whether the FDA and AstraZeneca should set aside the need for a domestic trial and instead use the foreign data that has already led to authorizations by key U.S. allies like the U.K. and EU.

Others argue it makes sense to wait for more data, given that there have been some questions about the AstraZeneca data, like whether it works in people over 65 and what the correct dose is. A dosing error in the trial has led to some confusion on those fronts.

Ashish Jha, dean of the Brown University School of Public Health, said it is “a reasonable decision under normal circumstances” for the FDA to wait for “cleaner” data from the U.S. trial.

But, he added, “there’s a reasonable question to ask: Are these normal circumstances?”

He noted that a more transmissible variant first identified in the U.K. looms as a threat over the U.S., and could lead to a “huge spike in cases” in the coming weeks. Public health experts are in widespread agreement that there’s now an urgent need to quickly vaccinate as many people as possible to try to blunt that spike.

But there are nowhere near enough doses for everyone in the U.S. with just the Pfizer and Moderna vaccines, so adding doses from AstraZeneca could provide a big boost. Johnson & Johnson applied for authorization on Thursday night, so it could also be added to the arsenal soon.

“That’s a debate we should be having,” Jha said, noting that regulators in the U.K. and EU that have already authorized the vaccine “clearly do have a high degree of scientific integrity.”

Some experts, however, say there are many unanswered questions about the AstraZeneca trials that need to be resolved first.

AstraZeneca’s “analyses are largely exploratory on a hodgepodge of different trials, doses, and timing of vaccines. We need clear prospective data from the ongoing U.S. trial to resolve this,” Eric Topol, a professor of molecular medicine at Scripps Research, wrote in an email.

“I don’t think there should be pressure” on the FDA to approve the vaccine before then, Topol said.

The FDA declined to comment on the specifics of the process around AstraZeneca’s vaccines, citing regulations about discussing individual companies seeking authorization, and referred questions to AstraZeneca.

“Data from the phase three U.K. trial has been shared with the FDA,” said AstraZeneca spokesman Brendan McEvoy. “As soon as the data from the U.S. phase three trial are available, they will be submitted to the FDA as well.”

Norman Baylor, a former director of the FDA’s vaccine office and now a pharmaceutical consultant, pointed to potential issues with the company’s data.

“We know that there have been some, for the lack of a better word, some bumps in the road, so to speak, with AstraZeneca, and I think FDA is probably trying to get a handle on that and really get a clear picture of that,” he said.

For example, regulators in Germany and France have said there is not sufficient data to justify authorizing the vaccine for people over 65, and have therefore only authorized it for people below that age cutoff.

Baylor said that if the FDA thought data from the foreign trial was sufficient, it could tell AstraZeneca, “‘Yeah, we think the data are sufficient now. Why don’t you guys go ahead and submit the data and we’ll start reviewing it?’”

“But it’s obvious that that’s not totally sufficient for the FDA or, yes, they would have done that,” he said. “They do want to see the data from the U.S. trial.”

It is also unclear how many doses of the AstraZeneca vaccine would be immediately available in the U.S. if it were authorized. The federal government has agreed to buy as many as 300 million doses, but the company has not said how many would be available in the short term.

Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, said there are tradeoffs, and that the FDA has “more transparency” in its decisionmaking and “would probably want to have a better handle on the data” than what is available from AstraZeneca so far.

Still, he said, “all of us would like to see everything go at a faster pace,” and “there’s something to be said about the U.K.’s approach.”

Like many aspects of the coronavirus pandemic, there’s also a political element surrounding the AstraZeneca vaccine debate.

Some on the right are particularly vocal about authorizing the vaccine now.

“There is no excuse that AZ’s vaccine that has already been approved in foreign countries and is in use there, shows great promise, can be rapidly produced, and where only a single dose is highly effective is not available to Americans now,” Brian Blase, who was a health care adviser to former President Trump, wrote in an email.

After Trump publicly attacked the FDA on Twitter during his presidency, leading to widespread condemnation from scientists about undermining the review process, President Biden has emphasized that he will not put any political pressure on the FDA.

In the end, Brown’s Jha said, the decision to wait for more U.S. trial data on AstraZeneca will likely be judged by how severe the spike from coronavirus variants ends up being.

“I do think the pressure on them is going to build if things start looking bad,” he said.