Yet again, AstraZeneca is in a crisis of its own making.
The latest in the drug manufacturer’s long string of mishaps and miscommunications came Tuesday, when top federal health officials accused the company of highlighting in a press release overly positive data about the efficacy of its coronavirus vaccine. It came after widely publicized snafus like administering incorrect doses during clinical trials and keeping U.S. regulators in the dark after pausing a trial entirely due to safety concerns.
And there were unlucky issues, too, like an investigation into blood clots in vaccine recipients, that were beyond AstraZeneca’s control.
The repeated gaffes have frustrated many public health leaders, who, given the available data, view the AstraZeneca shots as an effective and potentially transformative tool that could greatly help expand vaccine access around the world. Compared to other government-authorized vaccines, it’s cheap, and easy to manufacture and store. Millions of doses have already been deployed in other countries to protect people from Covid-19.
The tumult, however, has damaged the vaccine’s reputation and generated intense mistrust — so much that now, U.S. government scientists are openly expressing frustration with AstraZeneca over its transparency issues. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, told STAT on Tuesday that the press release data issue “was an unforced error by the company.”
Below, STAT outlines some of the key missteps and misfortunes that have tripped up the AstraZeneca Covid-19 vaccine, which, while approved in other countries, is still moving toward an authorization decision from U.S. regulators.
Not-so-clear lines of communication
There’s been a whole lot of hype around the AstraZeneca vaccine, even from the early days. In a July profile of the University of Oxford scientists who were driving much of the underlying science behind the shot, Bloomberg Businessweek raised the question of the vaccine candidate: “Could this be the one?”
But soon, AstraZeneca’s decisions cast a shadow over its Covid-19 work. In September, for example, officials at the Food and Drug Administration were stunned to find out from news reports — and not from AstraZeneca — that the company had halted its trials of the vaccine to investigate a potential side effect seen in one participant, the New York Times reported in December.
The communication issues have had real effects on the timeline of when AstraZeneca’s vaccine would reach different markets. One reason its U.S. trial was paused for weeks last year was because it took time for the company to offer the FDA data showing that the vaccines had not caused the neurological issues seen in two participants, the Times reported.
European countries have also had their share of frustrations with the company regarding supply issues, the Financial Times reported.
In November, AstraZeneca released data from separate trials in the United Kingdom and Brazil showing overall that its vaccine was 70% effective at protecting against symptomatic Covid-19. But digging into the data behind that top figure left experts perplexed.
Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. The company only later admitted the different dosing regimens were based on an accident, even as it defended the rigor of the trials overall. (Reuters later reported that the University of Oxford, AstraZeneca’s partner in developing the vaccine, didn’t disclose the dosing error to the clinical trial’s participants.)
The confusing analysis fed into broader questions about how AstraZeneca’s trial data could be interpreted. The company pooled results from different studies to arrive at efficacy figures, an unusual approach for these types of trials.
That was why there was so much anticipation for the results of AstraZeneca’s latest trial, which experts were looking to to provide a clean look at the efficacy of the vaccine. The results were released Monday, showing the vaccine reduced symptomatic Covid-19 by 79%, which seemed to validate the shot once and for all.
Then came Tuesday’s statement from the NIAID.
The latest snafu
On Tuesday, the NIAID issued a highly unusual, middle-of-the-night statement warning that AstraZeneca “may have included outdated information” in the data it published, and therefore “may have provided an incomplete view” of how effective the vaccine was.
The statement came after an independent monitoring board warned NIAID that the highly favorable data AstraZeneca published on Monday might be misleading, potentially having highlighted promising but outdated numbers instead of giving a more complete view of how well the vaccine works.
The trial produced better efficacy data than anticipated, with the vaccine reducing symptomatic Covid-19 by 79% and reducing severe illness and hospitalization by 100%.
But in a letter to AstraZeneca after the company announced its results, the independent monitors — called a data and safety monitoring board — said more up-to-date data indicated the vaccine was 69% to 74% effective.
“The DSMB is concerned that AstraZeneca chose to use data that was already outdated and potentially misleading in their press release,” reads the letter, as reported by the Washington Post. “The point that is clear to the board is that the [vaccine efficacy number] … they chose to release was the most favorable for the study as opposed to the most recent and most complete.”
In an interview with STAT Tuesday, Fauci said,“I was sort of stunned.”
“The data and safety monitoring board were concerned that the data that went into the press release by AZ was not the most accurate and up-to-date data,” Fauci said. “That is what the DSMB communicated to AZ in a rather harsh note. Having seen that letter we could not just let it go unanswered.”
Fauci added: “We just felt we could not remain silent. Because if we did remain silent, we could be understandably accused of covering something up. And we definitely didn’t want to be in that position.”
In a statement, AstraZeneca said the results that were released Monday were based on an interim analysis of trial data through Feb. 17. It said it would discuss with the DSMB its “most up-to-date efficacy data,” and said that, “We have reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis.”
In recent weeks, more than a dozen European countries took the dramatic step of pausing their rollout of the AstraZeneca vaccine — the only instance, to date, of governments halting distribution of a Covid-19 vaccine for safety concerns after it received initial authorization.
The concern: a number of anecdotal reports that people who’d recently received the shot developed blood clots, or experienced brain hemorrhages, soon after.
While the European Medicines Agency hasn’t ruled out a direct connection, it said last week there is no direct evidence that the AstraZeneca vaccine makes individuals more likely to experience blood clots. The benefit of the vaccine’s protection, it said, still far outweighs any potential risk posed.
Since then, countries including Germany, Italy, Spain, and France, have resumed deploying the vaccine. Other nations, including Denmark, Finland, and Norway, still haven’t lifted their temporary holds on the vaccine’s use.