AstraZeneca PLC may have released outdated information about trial results for its Covid-19 vaccine—a surprise disclosure that immediately cast doubt on the company’s assertion a day before that results showed the shot to be highly effective, reports Irish Times.
AstraZeneca vaccine trials
The early-morning statement from the National Institute of Allergy and Infectious Diseases came a day after AstraZeneca released interim data from large-scale U.S. trials that it said found its Covid-19 vaccine to be 79% effective in preventing symptomatic disease.
AstraZeneca, in its own statement, said it would update and reissue its trial results in 48-hours.
The results served as a short-lived vote of confidence in the shot, which has been clouded by uncertainty over previous, confusing efficacy results and large-scale production problems.
More recently, reported cases of rare blood clotting in Europe raised concerns about the vaccine’s safety, though European regulators have recommended its continued use. The U.S. trials showed no link with the vaccine and the NIAID statement didn’t raise questions about that finding or other safety-related issues.
Despite that reputational cloud, the shot is being rolled out widely outside the U.S., including across Europe where it is a key plank in efforts by governments there to accelerate its vaccination drive. Regulators there and in dozens of other countries have approved the shot for use. Early, real-world data from the U.K. has shown the vaccine to be effective in older recipients.
Concerns over clinical trials
NIAID, in its highly unusual statement, said an independent data monitoring board working with AstraZeneca in conducting its trials raised concerns about the company’s disclosures and had urged the drugmaker to work with it to ensure that the most accurate, up-to-date efficacy data would be made public.
NIAID said the monitoring board, an independent body that works alongside a drug company to conduct trials, “expressed concern that AstraZeneca may have included outdated information from that trial.” It said that could have “provided an incomplete view of the efficacy data.” The agency said it was urging AstraZeneca “to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible.”
Dr. Anthony Fauci, President Biden’s chief medical adviser and director of NIAID, said the data-monitoring board felt AstraZeneca’s press release about the results on Monday didn’t reflect the most recent and accurate data that board members had seen, and “they were concerned about it and they were really quite harsh about it.”
In an interview with The Wall Street Journal, he said a big factor in the decision to go out with a NIAID statement was that the agency had issued its own press release containing the AstraZeneca claims the same day.
“So, we felt it was absolutely necessary that we make a nonpejorative, nonaccusatory statement to say, ‘Hey, you better get together with the [data monitoring board] and work this out.’”
Dr. Fauci said that once AstraZeneca includes the more recent data, the effect on the shot’s reported 79% effectiveness will probably be modest. “That’s the ironic part about it,” said Dr. Fauci. “I mean, this is kind of unfortunate that this happened because at the end of the day, it’s still a good vaccine.”
Deviation from the scripted trial
The NIAID statement was a significant deviation from what are usually carefully scripted drug trial releases—done in coordination with medicines regulators and with regard to how they might affect public perception of safety, as well as how they might affect a company’s share price.
A drug monitoring board such as the one that raised its concerns typically works closely with a drugmaker to execute and analyze trial results.
AstraZeneca, which developed the vaccine in partnership with the University of Oxford, said in its own statement Tuesday that its disclosure on Monday was based on an interim analysis with a data cutoff as of Feb. 17. It said that it is now completing the validation of its statistical analysis and would “immediately engage” with the monitoring board “to share our primary analysis with the most up-to-date efficacy data.” AstraZeneca said it would issue results of that analysis within 48 hours.
Push back from Washington
The surprise statement raises new questions about the vaccine’s effectiveness against Covid-19 as it rolls out in millions of doses around the world.
It also further clouds AstraZeneca’s timeline for emergency use authorization in the U.S. It had said it hoped to apply to the Food and Drug Administration for authorization quickly so the vaccine, already being made in the U.S., could be administered there by May.
The push back from Washington is also the latest in a series of stumbles by AstraZeneca, one of the world’s biggest pharmaceutical companies, but with little experience in vaccines.
The British giant teamed up with the University of Oxford early last year and promised to roll out 3 billion doses of the two-dose shot this year, without profit. But since that pledge, the company has struggled to keep its vaccine trial and production efforts on track.
UK human trials
AstraZeneca released U.K. human trials last year, but data was muddled by confusing and incomplete explanations for a range of efficacy rates.
Oxford scientists and AstraZeneca executives initially said a subgroup of participants had been given a smaller initial dose, which they said appeared to boost the efficacy of the shot to 90%.
But as more details came out from U.S. officials, AstraZeneca disclosed that the reduced dosing was the result of an early vaccine-measurement error. U.K. regulators, in approving the vaccine for use, rejected the lower-dose explanation for the higher efficacy rate and stuck with recommending two full doses.
Several European governments restricted the shot to people 55 years or younger, based on sparse trial data showing how the vaccine worked in older adults. Those countries mostly relaxed that restriction after data from vaccinations in the U.K. showed the shot to be safe and effective in older recipients.
AstraZeneca then shocked European governments when it said it would miss by a wide margin its delivery promise of doses in the first quarter. The company had suffered manufacturing problems at a plant in Europe. Later, it promised to make up for the shortfall by importing doses, but then backtracked on that, too, citing export bans.
European politicians and some other officials have pilloried the company for the confusion and production setbacks.
AstraZeneca has pushed back against the criticism and defended the shot. Executives, including Chief Executive Pascal Soriot, have repeatedly pointed out that AstraZeneca is making more vaccines than any other drugmaker and is doing so without profiting.
Serious blood clots amid deaths
The latest reputational hit came earlier this month with reports of a small number of serious blood clots, including several reported deaths, in recently vaccinated Europeans. Several big countries, including France and Germany, paused their use of the shot until Europe’s main medicines regulator investigated the incidents.
Last week, that regulator, the European Medicines Agency, said it didn’t find evidence of a link between the clotting problems and the vaccine, but also couldn’t rule one out. It recommended a new warning be provided to healthcare professionals and the public about the AstraZeneca shot, to alert them of the need to monitor carefully for potential severe blood clots.
The U.S. provided more than $1 billion in funding to support the development of the AstraZeneca vaccine. The U.S. trial, which started recruiting volunteers there and in Chile and Peru in August, was standardized to meet FDA guidelines.
US-AstraZeneca drift
The relationship between AstraZeneca and U.S. officials has been tense in the past. The Wall Street Journal previously reported the FDA felt that AstraZeneca hadn’t informed it quickly enough when a participant in the U.K. trials got sick and that the company later was slow to provide follow-up information.
The FDA at the time paused U.S. trials, which were just getting under way. The trials were later resumed, but after a weekslong delay that pushed back significantly AstraZeneca’s ambitions of getting its shot quickly approved for use in the U.S.
As AstraZeneca responded to FDA questions during the U.S. trial pause, officials inside the agency got the impression the company was struggling to get its arms around the process of rapidly pulling together the necessary information, the Journal previously reported, citing a senior U.S. administration official.
Mr. Soriot defended the company’s disclosure of the sickness at the time and its interactions with the FDA.
100% effective vaccine
On Monday, AstraZeneca said its vaccine was 79% effective across all trial participants and 80% effective in participants aged 65 and over, a group previous AstraZeneca trials lacked in large numbers.
The shot was also found to be 100% effective in preventing serious illness and hospitalization across ages and ethnicities.
The U.S. trials provided the largest-scale clinical tests yet of the vaccine amid widespread scrutiny of its efficacy and reports of serious blood-clotting issues in a very small number of people in Europe who received the shot.
- While not yet approved for use in the U.S., the AstraZeneca shot is being rolled out widely elsewhere.
- The U.K. has administered 11 million doses.
- It is also being used in large-scale vaccination drives across Europe and in India, and has been approved for use in over 70 countries.
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Source: Irish Times
