All the scazzi in the US on the Astrazeneca vaccine. Report Nyt
What the New York Times wrote about the astrazeneca vaccine vicissitudes in the United States
Astrazeneca has promised the world more vaccines, at a lower cost, than all the more established vaccine manufacturers. He is discovering how difficult it can be to keep these commitments.
A public squabble this week with U.S. officials over the precise effectiveness of its Covid-19 has upset regulators and dented the pharmaceutical company's reputation in its largest market.
The diatribe has raised doubts among senior US medical officials about the company's data analysis, threatening to extend the regulatory review. Which is already months overdue after a separate standoff with the Food and Drug Administration in the fall over vaccine testing disclosures in the UK.
Wednesday evening, US time, AstraZeneca revised its vaccine efficacy estimate from large-scale US trials based on additional data, saying it was 76% effective in preventing symptomatic Covid-19, up from 79. % reported from an analysis on Monday.
The FDA, which must approve the vaccine before it is used in the United States, typically sends personnel to clinical trial sites to assess how data is compiled prior to any approval. The FDA now expects to send more employees to more sites than normal due to the level of distrust it has created, according to a senior US official, the NYT writes.
In Europe, meanwhile, the British-Swedish pharmaceutical company faces near-daily attacks from politicians who face public backlash over slow vaccinations and are angered by AstraZeneca's large shortages in manufacturing commitments.
Earlier this year, under pressure to make up for European manufacturing shortages, CEO Pascal Soriot called then US Health Secretary Alex Azar with a proposal. He asked if the United States would allow several million doses of the company's vaccine, which was not approved and unused in the United States, to be sent to Europe, according to a person familiar with the matter.
Azar replied that he would be willing to send two doses of AstraZeneca for every dose of Pfizer Inc.'s vaccine that European governments would be willing to send to the United States. Pfizer's vaccine had already obtained FDA clearance, with a proven efficacy rate of 95%. Azar did not respond to a request for comment.
It was not possible to determine whether Soriot ever shared the proposal with European officials. Europe has not received any finished AstraZeneca from the United States, according to European Union officials.
A spokesperson for AstraZeneca said governments have asked the United States for potential dose donations. "If these donation actions were to proceed, we would seek guidance from the US government on substituting doses for use in the US," he said.
In many ways, AstraZeneca, which developed the vaccine in collaboration with the University of Oxford, is delivering on its major promises. More than 70 countries, including the UK and much of the rest of Europe, have found the vaccine to be safe and effective. While not a major player in vaccines, AstraZeneca helped make an experimental vaccine ready for mass use in less than a year. The company has built a manufacturing and distribution network that is delivering doses to the poorest in the world. Unlike most of its big competitors with vaccines or vaccine candidates, it has promised to do all of this without profit. The vaccine has been crucial to the UK push which boasts one of the best per capita vaccination rates in the world.
But in crucial moments, company executives floundered in communications with governments, regulators, and the public. This has left a reputational shadow on the vaccine effort – an effort Soriot said reflects the company's desire to play a leading role in the fight against the pandemic.
In some cases, such as with its US trial data handling this week, AstraZeneca has deviated from what outside experts have said should be the standard disclosure protocol for a large pharmaceutical company. In dealing with European governments, AstraZeneca was put on the defensive by politicians, who portrayed the company as unreliable.
"The worst part of all of this is that we, as a planet, rely on their success," said Eric Topol, a professor of molecular medicine at Scripps Research in La Jolla, California, who has conducted clinical trials for 15 years and has written on the conduct of clinical trials. "It is extraordinary, when you have a vaccine that is the least expensive and the most orderly in the world, which should be given to billions of people, to have a self-destruct like this."
Soriot and other AstraZeneca officials expressed frustration that politicians and critics did not appreciate the magnitude of the task and the risks the company took, according to people familiar with their thinking. They have privately complained that they are not given enough credit for their unprofitable endeavors and ambitious goals they have set for global distribution, particularly in poor countries, and they deserve some leeway as they get going.
This week's standoff with US officials has dealt a new blow to the pharmaceutical company's credibility. On Monday, AstraZeneca released long-awaited efficacy data from a large-scale human trial in the United States, reporting that the injection was 79% effective across all age groups and ethnicities. The National Institute of Allergy and Infectious Diseases, which had overseen the studies, sent out its press release approving the figures.
Later that day, members of a government-appointed commission working with AstraZeneca to provide independent analysis of drug study data wrote to NIAID. The Data and Safety Monitoring Board raised concern that the company may have used outdated information that made the best results appear. The NIAID released a press release shortly after midnight on Tuesday urging the company and the board to work together to ensure the most accurate data is made public as soon as possible.
"That's the ironic part," said Dr. Anthony Fauci, President Biden's chief medical advisor and director of NIAID, in an interview earlier this week. "I mean, it's kind of unfortunate that this happened because, after all, it's still a good vaccine."
The company first stumbled last year when it released human test results in the UK. The data was confused by what many researchers and some government consultants have described as confusing and incomplete explanations for a range of efficacy rates.
Oxford scientists and AstraZeneca executives initially said a subset of participants were given a smaller starting dose, which appeared to increase the vaccine's effectiveness to 90 percent. They later revealed that the group was accidentally given a lower than expected dose.
British regulators, in approving the vaccine, rejected the lower dose explanation for the higher efficacy rate, and continued to recommend two full doses.
Aside from the discrepancy in dosage, AstraZeneca's range of efficacy, between 62% and 90%, was difficult to compare with US test results of rival vaccines, one from Pfizer and Germany's BioNTech and another from Moderna. . Both were found to be more than 94% effective in US studies.
Several European governments have restricted the injection to people aged 55 or younger, based on scant evidence showing how the vaccine works in older adults. Those countries mostly loosened that restriction after real-world data from the UK showed the injection is safe and effective in older recipients.
AstraZeneca surprised European governments in January when it said it would miss the volume it promised to deliver in the first quarter of this year by a large margin. The company had suffered production problems at a plant in Europe. He later promised to make up for the deficit by importing doses, but then backtracked on that too, citing export bans.
European politicians pilloried the company over confusion and production setbacks, while directly mocking the vaccine. French President Emmanuel Macron at one point called it "near-ineffective".
In defense of the company, executives including Dr. Soriot have repeatedly said that AstraZeneca is making more vaccines than any other pharmaceutical company, and doing it without profit.
Another setback came earlier this month with reports of a small number of serious blood clots, including several reported deaths, in recently vaccinated Europeans. Several large countries, including France and Germany, paused the use of the vaccine until Europe's leading drug regulator investigated the incidents.
Last week, this regulator, the European Medicines Agency, said it had found no evidence of a link between clotting problems and the vaccine, but also couldn't rule out one. He said the benefits of the vaccine outweigh the risks, and that severe clotting occurs naturally in the population. The agency recommended providing a new warning to healthcare professionals and the public to alert them to the need to closely monitor potential serious blood clots.
AstraZeneca said US trials did not identify any increased risk of serious blood clots. In its statement on Tuesday, the NIAID did not raise questions about the results of the trial regarding blood clotting or any other safety concerns, but did cite incomplete information regarding the vaccine's effectiveness.
The United States has provided more than $ 1 billion in funding to support the development of the AstraZeneca vaccine. The US trial, which began recruiting volunteers there and in Chile and Peru in August, has been standardized to meet FDA guidelines.
The relationship between AstraZeneca and US officials has been strained in the past. Last year, the FDA felt that AstraZeneca didn't notify it quickly enough when a British trial participant fell ill, the Wall Street Journal reported, and that the company was slow to provide follow-up information.
AstraZeneca has put on hold the US and global studies, which had just started. Testing resumed after a weeks delay that pushed back AstraZeneca's ambitions to get its vaccine quickly approved for use in the United States.
Dr. Soriot defended the company's disclosure of the disease and its interactions with the FDA.
Since then, skepticism has increased among government health officials about the accuracy of AstraZeneca's claims about the trial results, according to senior US officials.
Officials from the National Institutes of Health, an umbrella agency that includes NIAID and helps fund, conduct, and direct U.S. basic medical and scientific research, have questioned why AstraZeneca has hesitated to provide more data. recent in its US trial, according to people familiar with the matter.
AstraZeneca said Tuesday that it has provided data analysis through Feb.17 and that it would “immediately engage” with the review committee to share its analysis of the “most up-to-date efficacy data”.
The trial's safety controllers wanted AstraZeneca to look at the data starting in mid-February, but also the data accumulated since then, people familiar with the matter said.
The monitoring committee that complained about the data is the same independent group of physicians and other medical experts who have worked with other vaccine manufacturers who have accepted US funding, including Moderna, Johnson & Johnson's Janssen, and Novavax Inc. His task is to review test data and provide independent evaluation of test results. None of the previous studies have produced major scientific controversies, at least not the ones that have gone public.
The data the monitoring committee was reviewing showed an effectiveness of about 70-79 percent, a number that changed regularly based on the new data, according to senior government officials. In recent days, the scrutiny committee has been discussing with AstraZeneca which number to use in any public disclosure, according to one such official, and auditors have been adamant that the number should not be more than 75%, reflecting data after 17. February.
AstraZeneca's analysis was different, according to one person familiar with the company's internal discussions. Technically, the council's role is strictly to make recommendations, with no authority to dictate what data to disclose to the public on a drug manufacturer. In practice, it can be difficult for companies to reject board recommendations due to the stamp of approval that comes with its approval.
AstraZeneca executives felt pressure to release some US test results as soon as possible, even if they were preliminary, people familiar with the matter said.
In its Wednesday night press release on the results of the US trial, AstraZeneca said the top-line efficacy result across the trial was marginally lower than previously suggested. He said two doses were 76 percent effective in preventing symptomatic Covid-19, up from 79 percent on Monday's preliminary report.
Among people aged 65 and over, the vaccine was 85 percent effective, up from 80 percent on Monday's report. In both analyzes, the vaccine was found to provide 100% protection against severe illness and hospitalization, even though the numbers of such severe cases were small.
AstraZeneca said it plans to submit the results to the FDA by mid-April in the hopes of obtaining authorization to use the vaccine in the United States.
(Extract from the foreign press review by Eor Comunicazione)
This is a machine translation from Italian language of a post published on Start Magazine at the URL https://www.startmag.it/mondo/accino-astrazeneca-usa-nyt/ on Sun, 28 Mar 2021 06:00:32 +0000.