LONDON – UK approval for the use of Covid-19 vaccine, developed by Oxford University and
AstraZeneca
The LPC marks a victory for both British institutions, but comes after a stalemate that has questioned public opinion about inclusion and put pressure on the partnership itself.
After Wednesday’s approval of the regulations, the partners must convince the medical authorities in the United States and elsewhere that their mistakes are over and that their vaccine, although not as effective as injections from two competitors that have already been exhausted, can play an important role in containing the pandemic.
The partners promised to distribute their vaccine in large quantities and sell it at low prices during the pandemic. In the U.S., AstraZeneca plans to submit data from a major U.S. clinical trial to the Food and Drug Administration by February, said one person familiar with the study.
The partners hope to have the approval of the whole of Europe by February, and the green light could soon be given in Australia, the man said. AstraZeneca’s production partner in India has submitted an application for approval in this country. It all depends on the diet.
The complexity of these plans raises doubts about the partners’ ability to manage their ambitious project themselves. At the end of November, they published the results of a late study showing a wide range of efficacy levels depending on dose and age group. The presentation about the unusual and unexpected half dose given to some subjects, which was not fully explained, caused confusion and scepticism about the vaccine.
UK regulators on Wednesday welcomed the vaccine’s promise to help end the pandemic, but rejected the half-dosage regime used by Oxford and AstraZeneca, citing its greater efficacy and saying the data did not support the results. According to a government health advisor, the complexity of the vaccination trials has made the conclusions on efficacy and dosage more difficult than he and his colleagues usually find.
Oxford officials demanded stricter controls on sharing vaccine information, said people familiar with interactions between partners. The lawsuit was filed after a number of university employees found that AstraZeneca had handled the test reports incorrectly.
According to some of his relatives, friction in the academic-business partnership was inevitable, given the economic and political interests involved, the risks of failure for reputation and the sheer complexity of the task. Errors on both sides have sometimes made working with wire difficult. Some skeptics have questioned AstraZeneca’s prospects of regaining sufficient credibility to gain broad public support in the U.S. or even to obtain FDA approval in the near future.
When a rigorous academic review of the study’s data was scheduled for publication in early December, Oxford officials concluded that publication would take place on Oxford terms.
John Bell,
told the CEO of AstraZeneca a senior researcher from Oxford who negotiated the contract for the vaccine between Oxford and the pharmaceutical company.
Pascal Soriot
that Oxford wanted to put its top scientists in the spotlight when the company revealed the results of the British study, according to people familiar with the phone conversation between them.
A day before the scientific report was published in The Lancet, Dr. Bell told his colleagues that the confusing publication of the trial data in November would undermine trust in the vaccine, according to people familiar with the conversation.
Professor John Bell of Oxford expressed the wish that the university’s scientists would be closely involved in presenting information on the Oxford vaccine and AstraZeneca.
Photo:
Mary Turner of the Wall Street Journal
The Oxford requirements were to have more influence on the Food and Drug Administration. According to a senior U.S. official, some FDA officials found that AstraZeneca had failed to report the case of a trial participant in the United Kingdom who fell ill early enough, and that the company was late in providing follow-up information.
In an interview, Professor Bell said that he wanted the university’s lead clinical researcher on the vaccine to be present at AstraZeneca’s next meeting with U.S. regulators. The FDA likes to talk to vaccinators, Professor Bell said. We should always be on stage together, so that we can always meet and work together.
AstraZeneca had always intended to fully involve Oxford’s scientists in the publication of a rigorous academic review of the trial data, and business leaders supported Oxford’s participation in the FDA meeting, said a person familiar with the executive’s deliberations.
The University of Oxford and AstraZeneca have a common goal: to bring billions of doses of our vaccine to the world for free to help the pandemic behind us, according to an AstraZeneca spokesperson. Our strong relationships and complementary skills have enabled us to reach a rapid pace in recent months.
Professor Bell stated that his relationship with the management of AstraZeneca was positive and described the collaboration as successful. We realise that working with university partners is not always easy for large companies, he said through an Oxford spokesperson. Professor Bell described his collaboration with the CEO of AstraZeneca as admirable and expressed the hope that we would both show the right level of mutual respect.
Historic Oxford University City
Photo:
Mary Turner of the Wall Street Journal
AstraZeneca’s office in Cambridge
Photo:
Alastair Grant/Presse Associée
From the outset, Oxford academics, supported by the public, took an offensive view of the lucrative idea of the pharmaceutical world, which sparked a lively debate among academics. For weeks in the spring, scientists debated which company to bring in before they brought in AstraZeneca at the end of April.
AstraZeneca had little experience with vaccines, but supported Oxford’s core objectives. It has agreed to produce and distribute billions of times more doses of vaccine than any other Western pharmaceutical company, on a non-profit basis in the event of a pandemic, not even in the Third World. The British government wanted a national vaccine manufacturer. AstraZeneca is located in Cambridge.
Although studies have shown that the efficacy of the vaccines is lower than that of the vaccines developed by the company.
Pfizer Inc.
and Germany
BioNTECH SE,
also
Moderna Inc..,
The picture of Oxford and AstraZeneca has its advantages. It requires normal cooling for several months of storage and distribution. Combined with low prices and high production volumes, it is particularly suitable for poor countries and hard-to-reach populations.
In the meantime, it could also be a blessing for rich countries worried about vaccination shortages. AstraZeneca has pledged to provide three billion doses by 2021, enough to vaccinate 1.5 billion people.
Some of the initial difficulties were due to the different methods used in academia and industry.
Last January, as scientists began to understand the coronavirus, Oxford researchers worked around the clock to develop a vaccine that would inject weakened chimpanzee viruses as vehicles with the coronavirus-specific genetic code to trigger human immunity. The university then used its own small drug production facility to pump out enough drugs for testing.
In April Oxford began human trials in the UK, which were later extended to Brazil and South Africa. The design of the research at Oxford was different from that of typical large pharmaceutical companies and the data collection methods were different.
Other registration
Oxford-AstraZeneca’s Covid-19 vaccine is the second vaccine authorised in the United Kingdom and the third in the West.
Vaccines in phase 3 of clinical trials
Covid-19 Genome sequencing
The World Health Organization declares Covid-19 a global pandemic…
University of Oxford/AstraZeneca
Approved for use in the United Kingdom.
Sinopharm (joint development of two vaccines with the government agencies Wuhan Institute of Biological Products and Beijing Institute of Biological Products)
Operational plan until the end of the year
Operational plan until the end of the year
CanSino Biology/Chinese Academy of Military Medical Sciences
Exempted for military purposes for a period of one year
They are expected to be available in the United States in early 2021.
Russia started the operation in December
Gamaleya Research Institute
A third testing phase in the United States is expected to start soon.
Anhui Zhifei Longcom Biopharmaceuticals/China’s Academy of Sciences
Covid-19 Genome sequencing
The World Health Organization declares Covid-19 a global pandemic…
University of Oxford/AstraZeneca
Approved for use in the United Kingdom.
Sinopharm (joint development of two vaccines with the government agencies Wuhan Institute of Biological Products and Beijing Institute of Biological Products)
Operational plan until the end of the year
Operational plan until the end of the year
CanSino Biology/Chinese Academy of Military Medical Sciences
Exempted for military purposes for a period of one year
They are expected to be available in the United States in early 2021.
Gamaleya Research Institute
Russia started the operation in December
A third testing phase in the United States is expected to start soon.
Anhui Zhifei Longcom Biopharmaceuticals/China’s Academy of Sciences
Covid-19 Genome sequencing
The World Health Organization declares Covid-19 a global pandemic…
University of Oxford/AstraZeneca
Approved for use in the United Kingdom.
Sinopharm (joint development of two vaccines with the government agencies Wuhan Institute of Biological Products and Beijing Institute of Biological Products)
Operational plan until the end of the year
Operational plan until the end of the year
CanSino Biology/China Academy of Military Medical Sciences
Exempted for military purposes for a period of one year
They are expected to be available in the United States in early 2021.
Gamaleya Research Institute
Russia started the operation in December
A third testing phase in the United States is expected to start soon.
Anhui Zhifei Longcom Biopharmaceuticals/China’s Academy of Sciences
Covid-19 Genome sequencing
The World Health Organization declares Covid-19 a global pandemic…
University of Oxford/AstraZeneca
Approved for use in the United Kingdom.
Sinopharm (joint development of two vaccines with the government agencies Wuhan Institute of Biological Products and Beijing Institute of Biological Products)
Operational plan until the end of the year
Operational plan until the end of the year
CanSino Biology/China Academy of Military Medical Sciences
Exempted for military purposes for a period of one year
It should be available in
The total cost of the project is estimated at $500,000 at the beginning of 2021.
Gamaleya Research Institute
Russia used
in December
A third testing phase in the United States is expected to start soon.
Anhui Zhifei Longcom Biopharmaceuticals / Chinese Academy of Sciences
In the spring, the biotechnological spin-out in Oxford, founded by the two university scientists behind the vaccine, also grew rapidly and started clinical trials in the United States. But then AstraZeneca came in as a partner and took responsibility for planning the American tests. The US government has agreed to pre-order at least 300 million doses in an agreement now estimated at $1.6 billion, providing essential support for clinical trials.
AstraZeneca faces complications in complying with several U.S. government officials regarding the trial parameters. It was not until August that he began recruiting 30,000 American volunteers. Some rival pharmacists got off to a faster start and took advantage of it.
After the first week of September – the second in a row – suspicions of neurological disorders in subjects in a British clinical trial emerged, AstraZeneca and Oxford suspended the worldwide studies. In the UK the interruption lasted less than a week, but in the FDA-controlled US trials the interruption lasted for weeks.
FDA officials learned of the illness and paused the study two days later when reporters called, according to a person familiar with the case. Agency officials only received a full briefing from AstraZeneca along with the media, people said.
The CEO of AstraZeneca, Dr. Soriot, spoke about the pause in the study and the theories about the disease in a non-public conversation with customers of a large investment bank. The discussion got out of hand.
Pascal Soriot, CEO of AstraZeneca
Photo:
Zach Gibson/Bloomberg News
The same week, during a public press conference, Dr. Soriot defended his position and that of the company: When you do clinical trials, you essentially inform the regulatory authorities, he said. You don’t publish, you don’t make big announcements in the press. I mean, it’s a scientific process.
Ideally, you wouldn’t find out by a phone call from an investor, he said.
Saad Omer,
a specialist in infectious diseases and director of the Yale Institute of Global Health. It’s an environment where the sausage is cooked for everyone.
When AstraZeneca answered questions during the U.S. judicial recess, FDA officials felt that the company was trying to quickly bypass the process of gathering the necessary information, according to a senior U.S. government official.
A complication was the time-consuming problem of reformatting the detailed data from the Oxford study from the UK to satisfy the FDA, according to those involved in or aware of the process. The U.S. agency requested large amounts of additional data from AstraZeneca, a process that, according to Dr. Soriot in an interview in November, was time-consuming.
They asked for a lot of data that did not necessarily relate to the case itself, but to the design of the clinical trial, the safety parameters and the information about the vaccine, he said. There have been major differences in the way Oxford and AstraZeneca perform surgical procedures. The FDA refused to comment.
Clinical trials in the United States resumed in the last week of October after an interruption of almost seven weeks. AstraZeneca executives and Oxford researchers remained optimistic about the limited commitment at the end of the year.
The 23rd. In November they published the preliminary results of the final phase of the studies carried out in the United Kingdom and Brazil. At the time, the public perception of the vaccine’s success had changed because of Pfizer’s more than 90 percent effectiveness rate.
Biotechnology
and Moderna.
Oxford and AstraZeneca stated that the data from the trials showed that their vaccine was 62-90% effective. The subgroup of subjects receiving a lower initial dose under the two-dose regime was more numerous.
A volunteer received an injection in a South African hospital as part of a clinical trial for a vaccine developed in collaboration with AstraZeneca at Oxford University.
Photo:
Siphiwe Sibeko/Presse Associée
Scientists and healthcare professionals said they couldn’t satisfactorily explain why the first half dose was more effective, but they called it good news and said they would study it further. The partners did not report that the researchers had given some subjects a lower initial dose due to differences in the measurement of vaccine concentrations, so that the lower dose was unexpectedly low.
The other thing they didn’t reveal in the beginning was that those who received the lowest dose and showed 90% efficacy were all 55 years of age or younger. A U.S. government official noted that one day later Oxford and AstraZeneca launched a campaign to avoid confusion and criticism about their limited disclosure.
The next few days the duel versions were behind the first half dozen. AstraZeneca stated that this was due to a first mistake in the Oxford investigation, but did not affect the results. The vaccine will contain the pandemic, whether it is 60%, 70% or 90% effective, said Mena Pangalos, then head of biopharmaceutical research and development at AstraZeneca, in an interview. I think we’re losing sight of the importance of this story.
But
Adrian Hill,
The chief Oxford scientist behind the vaccine told the investors of the Oxford spin-out, which was co-founded by Vaccitec Ltd. (Vaccitech Ltd.), which collects royalties on the vaccine, that there was no dosing error. Let me make it clear that we really knew what we were doing and how much we were giving, he told investors in a video call that was seen by the Wall Street Journal.
Professor Hill said that early declines in production caused a decrease in vaccine stocks and made the half-dose regime attractive, which led researchers to discover that it caused less serious side effects. So it was deliberate, it wasn’t an accident, he said. He refused to comment on the article.
In the end, Oxford gave more details. The spokesman said that there were no problems with the production of vaccines, but that the different materials used and the different methods of measuring vaccine concentration led to uncertainties in the final dosage.
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To be conservative, the critic said the researchers reduced the dose with what they thought was the best estimate. This has led to an unplanned low dosage, said an Oxford spokesman. He stated that the lower dose was only fully understood when some of the subjects in the studies showed lower amounts and less serious side effects. Regulators have authorised the use of the first half dose for the study subgroup.
But that didn’t get Britain out of its hurdles on Wednesday. The regulators approved the plan for a full dose, but rejected the plan for half a dose. A government health advisor stated that the 90% effectiveness may have more to do with the longer interval between doses than with the size of the dose itself. He stated that the conclusion could not be reached without more data.
Another consultant said on Wednesday that interpreting data on the Oxford-AstraZeneca vaccine is complicated by the design of trials in different countries with different age groups, dose intervals and dose sizes. Even the results, published in the Lancet three weeks ago, cannot be fully reconciled with the latest analysis, according to the consultant. The consultants said they believe the vaccine is at least safe and effective.
Home stay campaign warns Londoners for new strain of Covid 19 virus
Photo:
Dinendra Haria/London News Pictures/Zuma Press
Oxford and AstraZeneca said they would further investigate why halving the first dose gave better results. Meanwhile, FDA officials are skeptical about the explanation for the half dose, according to a U.S. government official, and are waiting for final data for the U.S. trial.
-Thomas M. Burton and Joseph Walker contributed to this article. -Thomas M. Burton and Joseph Walker contributed to this article.
E-mail Jenny Strasburg at [email protected].
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