AstraZeneca: How confidence in one of the leading vaccine candidates has been weakened

LONDON.- The AstraZeneca and Oxford vaccine Last year, she was one of the strongest candidates to pull the world out of the shock caused by the coronavirus pandemic. But a series of setbacks delayed the release of results and weakened confidence in the British formula, which has been overshadowed by other drugs, such as Pfizer or Moderna.

Here is an overview of the main achievements and milestones in the UK vaccine development process.

At the start of the pandemic, researchers at Oxford developed the vaccine using the genetic engineering of an adenovirus that normally infects chimpanzees. When they administered the vaccine to the monkeys, they discovered that animals protected against disease.

The vaccine relies on the virus’s genetic instructions to build the spike protein. But unlike the Pfizer-BioNTech and Moderna vaccines, which store instructions in single-stranded or helical RNA, the Oxford vaccine uses DNA double helix. The researchers added the coronavirus spike protein gene to another virus called adenovirus. Adenoviruses are common viruses that often cause colds or flu-like symptoms. The Oxford-AstraZeneca team used the modified version of a chimpanzee adenovirus, known as ChAdOx1. Can enter cells, but cannot replicate inside.

In April, the researchers continued with a phase 1/2 test. Vaccine developers did not detect any serious side effects in the trial, although they observed that the vaccine produced antibodies against the coronavirus and other immune defenses.

The vaccine began phase 2/3 trials in Great Britain and India (where it is known as Covishield). In addition, AstraZeneca subsequently initiated Phase 3 trials in Brazil, South Africa, United States and Japan.

Everything seemed to be going smoothly until the company voluntarily suspended global Phase 3 trials in September to allow an independent committee to review the safety data after a volunteer in Great Britain will have a serious adverse reaction.

Following a safety assessment of the vaccine, AstraZeneca resumed trials a few days later in Great Britain, Brazil and South Africa. Japan and the United States did so the following month.

The next setback came in late November, when the company released preliminary results and acknowledged a dosage error in trials of its vaccine against Covid-19. According to the study, the percentage of effectiveness was close to 62% in those who received two full doses and 90% in those who received half the dose on their first injection.

AstraZeneca admitted that the half dose was initially an “error”. The plan was for patients in the UK trial to receive two full doses one month apart, but some received half for their first injection. This appeared to increase the effectiveness of the vaccine, which Dr Mene Pangalos, an executive at the pharmaceutical company, described as “Serendipia”.

But fewer than 2,800 participants received the smaller regimen, compared to nearly 8,900 participants who received two full doses. For many outside experts, this undermined the credibility of the results because tightly calibrated clinical trials were not designed to test the effectiveness of a half-potency starting dose.

Additionally, researchers at AstraZeneca and Oxford were unable to answer the most important questions: why was there such a large variation in vaccine efficacy at different doses, and why a single dose smaller seemed to produce much better results?

Crucial information was also missing. The company said the initial analysis was based on 131 symptomatic cases of Covid-19 that appeared in study participants. But he did not break down the number of cases found in each group of participants: those who received the medium-strength starting dose, the regular starting dose, and the placebo.

Then Moncef Slaoui, head of Operation Warp Speed, the US initiative to speed up coronavirus vaccines, highlighted another limitation in AstraZeneca data. On a call with reporters, he suggested that participants who received the initial half-strength dose were 55 years of age or younger.

That same month, Pfizer and Moderna said their vaccines, which used a technology known as “messenger RNA,” appeared to be around 95% effective.

On December 2, the drug received a new blow when Britain, home to AstraZeneca and Oxford, has approved the use of the first coronavirus vaccine: that of Pfizer and BioNTech.

It was almost a month later on December 30, when the country finally authorized emergency use of the AstraZeneca vaccine, the first to do so with Argentina, despite the uncertainty about the efficacy results of the trials.

On January 3, 2021, India approved a version called Covishield, prepared by the Serum Institute of India.

On January 29, the European Medicines Agency (EMA), the decentralized agency responsible for evaluating and monitoring applications for marketing authorization for medicines in the European Union, approved the formula for AstraZeneca and Oxford. However, A large part of the countries in the bloc (Norway, Denmark, Iceland, the Netherlands, France, Germany and Belgium) have said they will not use this vaccine for adults over 65 at this time.. The measure is due to the lack of information on side effects in the population above this age.

Meanwhile, AstraZeneca continued to analyze data from its trials and released another report on February 2, 2021, which has yet to appear in a medical journal. They found out that two doses 12 weeks apart had an efficacy rate of 82.4%. Not only did the vaccine keep people from getting sick, it also reduced transmission of the virus, a promising sign that vaccines could curb the pandemic.

On February 16, the World Health Organization recommended the vaccine for emergency use in adults over 18 years of age.

In March, Covax, the Covid-19 Global Vaccine Access Fund, began distributing millions of doses of the vaccine to low- and middle-income countries.. AstraZeneca is expected to seek emergency use authorization from the Food and Drug Administration (FDA) when its Phase 3 trial in the United States yields results, possibly this month.

The company expects a total annual manufacturing capacity of 2 billion doses.

In an unprecedented move in the field of the coronavirus vaccine, AstraZeneca announced on December 11 that would collaborate with the Russian creators of the Sputnik V vaccine, which is also made from adenovirus, to see if a combination with Sputnik V might increase the effectiveness of the Oxford-AstraZeneca vaccine. The trial began in February 2021.

In contrast, on February 13, the University of Oxford launched clinical trials to verify efficacy in children aged 6 to 17 of the anticovid vaccine that it developed with the pharmaceutical company AstraZeneca, in what is considered to be the first trials in the world in minors of this age group. For these pediatric trials, 300 volunteers have been recruited, of whom up to 240 will receive the Oxford / AstraZeneca vaccine and the remainder a control vaccine against meningitis.

With the appearance of new variants, the problems resurfaced. The South African government decided to suspend the application of the vaccine developed by the University of Oxford and AstraZeneca in February after a study showed very limited efficacy against the variant of the coronavirus (501Y.V2 or B.1.351 ) discovered in the country.

According to this study, the solution only offered about 22% effectiveness against mild and moderate cases of the variant, 50% more contagious.

As small, Norway, Denmark and Iceland have announced the “precautionary” suspension of AstraZeneca vaccines to study clots in inoculated patients. Italy, meanwhile, has banned the application of a specific batch of vaccine.

Authorities have not indicated the number of reports of blood clots, but Austria has stopped using AstraZeneca vaccine batch, the same one that Italy has stopped using today, while a death from bleeding disorders and disease from pulmonary embolism are under investigation.

However, the European Medicines Agency (EMA) said today that there is no evidence to date that Covid-19 vaccines cause more blood clotting in people who receive them.

THE NATION

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