The latest blow to AstraZeneca’s tortured effort to bring the Covid-19 vaccine to the world came with a brief statement issued Tuesday at 10pm in Washington.
In an unprecedented late-night intervention, the National Institutes of Health warned that an independent committee of experts overseeing a major U.S. vaccine study “expressed concern that AstraZeneca may have included outdated information” when it released the release results to Monday.
The dispute between AstraZeneca and independent scientists – who sit on the trial and security oversight committee or the DSMB – has focused on whether the company made a mistake in publishing data collected before the February break, instead of including more recent data.
Data up to Feb. 17 showed the vaccine was 79 percent effective in stopping symptomatic Covid-19, the company said in a statement Monday morning.
But in a letter to AstraZeneca later Monday, which was copied to the NIH and another U.S. government agency funding the trial, the DSMB said it thought a broader analysis that included up-to-date results would show a lower efficiency rate of between 69 percent and 74 percent, according to to the person who saw it.
Anthony Fauci, a senior NIH official, told the Financial Times that the agency “does not accuse anyone of anything,” adding: “[We are] just to say very, very honestly and simply, to invite the company to work with DSMB to review the data and ensure that it is the most accurate and up-to-date data published to the public. ”
AstraZeneca responded to the NIH statement by promising to release the final set of trial data within 48 hours.
The vaccine has already been approved for use in the EU, the UK and other countries, and the primary purpose of this study is also to provide a green light to regulators in the US.
But the U.S. trial has gained importance that goes beyond paving the way for the Food and Drug Administration’s approval, a confirmation that Pascal Soriot, CEO of AstraZeneca, has long sought.
Instead, the study offered a buyout option for a company accused of harassing previous trials, leaving unanswered questions about whether the sting is equally effective in older people.
It also hoped the U.S. study would boost global confidence in the vaccine by easing concerns about whether it causes rare but potentially deadly blood clots, prompting several European countries to suspend its introduction.
According to a person familiar with the issue, AstraZeneca was “under pressure” to release the findings Monday to prove the vaccine had strong efficacy in people 65 years of age and older. The drugmaker was also concerned that it could be “accused of sitting on data and not being transparent,” they added.
However, far from quelling concerns over the AstraZeneca sting, the findings of the U.S. interrogation caused even greater confusion.
Art Caplan, a professor of medical ethics at New York University who has served on about 20 DSMBs, said the scientists’ decision to challenge AstraZeneca’s claims about efficacy was “very close to nuclear intervention.”
DSMB members must have been “deeply concerned that the data they saw was not taken into account” in a press release, Caplan added. “AstraZeneca’s next move will determine the fate of the vaccine. If they mess it up, the vaccine may not be able to be used in some countries. “
This is not the first time the DSMB has questioned how AstraZeneca handled trial data, according to a person familiar with the relationship, who said the scientists had become “impatient” with the company. But now smoldering tensions have spilled over into the public.
AstraZeneca, a UK-based pharmaceutical group that developed a vaccine invented at the University of Oxford, has huge ambitions for its introduction: it wants to produce more stings than any other company and sell them at a non-profit price.
But AstraZeneca has struggled in the spotlight compared to other vaccine manufacturers, including a group of smaller and younger companies such as Moderna, an American biotechnology group.
AstraZeneca’s efforts have been mitigated by difficulties in understanding how she cut and shredded data from her first phase 3 trial in November, an episode that echoes the latest drama, full of confusing press releases that have frustrated scientists. The company is also embroiled in a dispute over production shortages in the EU.
When AstraZeneca released the results of the U.S. trial early Monday morning in Europe, it seemed as if the data would finally resolve many long-standing doubts about the vaccine.
With an overall efficacy rate of 79 percent, the statement said the vaccine was 100 percent effective in stopping severe illness and hospitalization – an improvement in an earlier phase 3 trial. Nor was there evidence of problematic blood clots.
Armed with the trial findings, executives went to U.S. television studios to interpret the benefits of the sting, and Ruud Dobber, U.S. President of AstraZeneca, told CNBC’s business news channel that the company was “thrilled.”
But behind the scenes, things were about to go wrong. Hours after the press release, a frustrated DSMB contacted AstraZeneca, the NIH Faucia, and the U.S. Agency for Advanced Research and Development in Biomedicine, or Bard, which provided funding for vaccine development, according to people familiar with the development.
AstraZeneca tried to address the DSMB’s concerns, and the person briefly suggested that Soriot had taken the lead in resolving the dispute. “Obviously he would have preferred it not to have happened, but he is fully focused on fixing it,” the person said.
The dissenter suggested that the DSMB saw only “raw data”, where Covid-19 cases were not confirmed by a positive test result. Once “judged”, it could be determined that the positive case was in fact the flu or that someone simply lost their sense of smell, the person added.
Now AstraZeneca is accelerating through the final analysis. “It’s a painful way to spend 48 hours,” the person said.
Another person familiar with the situation said that, prior to the release of the provisional data on Monday, AstraZeneca was already in the process of assessing newer data that arrived after the February 17 border point. The company does not anticipate that the newer data will result in a significant change in its efficiency conclusions, they added.
The person pointed out that the company had always said that it would conduct a so-called interim analysis and twice described the findings in its press release as “temporary”.
“This is not just something they cooked. . . It was very clear that more data was coming, “they said. Efficiency data released on Monday is likely to be “pretty close to where it will end up in the final analysis”. they added. “If the numbers are moving after all, they probably won’t move en masse.”
However, that does not explain how the company eventually angered the scientists at DSMB. Dan Barouch, a Harvard professor and clinical trial researcher in the Johnson & Johnson vaccine trial, said it was unusual and “not optimal” that the board did not see what would be published.
“DSMB usually does the analysis and provides it to the company, and in this case to the government. . . The statement that comes out is a statement that everyone agrees on in advance, ”Barouch added.
One observer said the company may have been trying to “be simple” after the debacle in November, when the company and Oxford reported three separate efficiency numbers.
In the U.S., the White House was concerned enough to request a meeting with the NIH. The impact will also be felt in Europe, where health officials have hoped to read with clean, easy-to-understand data to help increase public confidence in the vaccine. One global health official asked, “How does AstraZeneca manage to screw up every time?”
Shares of AstraZeneca on the London Stock Exchange closed 1.76 percent lower on Tuesday, as investors, who do not profit from the vaccine during the pandemic, were upset that resolving the situation could damage the company’s broader reputation.
Dan Mahony, co-president of healthcare for Polar Capital and investor of AstraZeneca, said the company was developing the vaccine for “the right reasons”, but described the latest developments as “frustrating”.
He added: “It’s getting a bit of a PR headache and it seems to suck up a lot of management time. . . As an investor do you think it really paid off? You don’t want to constantly fight fires, especially because of something that doesn’t bring you a lot of money. “
Additional reporting by Kiran Stacey of Washington