Virus World

AstraZeneca’s vaccine study is being investigated further by the Food & Drug Administration (FDA) after a participant experience a suspected adverse reaction to the drug. This could put additional delays on the British drugmaker’s late-stage trial. Meanwhile, European regulators are set to announce the start of AstraZeneca’s review in Europe as soon as this week - the first vaccine to undergo EU approval. AstraZeneca’s CEO said on September 10 the vaccine would be ready by the end of the year or early next year, despite the COVID-19 trial halting due to the illness.

The US Food and Drug Administration (FDA) has broadened its investigation into the suspected adverse reaction of a participant in AstraZeneca's COVID-19 vaccine trial, whilst European regulators are set to announce its review as soon as this week. The FDA also wants to examine results from earlier studies of other vaccines produced by the same scientists of the AstraZeneca vaccine to see if similar side effects have emerged, three sources with knowledge of the trial told Reuters on Wednesday. But these checks don't mean the agency suspects safety concerns with any of the vaccines, the people said. "It just shows that the FDA is being thorough," one of the sources told Reuters. AstraZeneca's vaccine study, which is said to be one of the most advanced COVID-19 vaccines in the world, could be delayed even further due to the wider probe into safety issues carried out by the FDA. The drugmaker's phase three coronavirus vaccine trial was put on hold on September 6 following a serious illness of a participant in the UK who has reportedly come down with a rare spinal inflammatory disorder called transverse myelitis. Trials have now resumed in the UK, South Africa, India and Brazil, but US authorities are yet to give AstraZeneca the all-clear to restart trials. The US government has pledged up to $1.2 billion to support AstraZeneca's vaccine development and has secured 300 million doses for the whole country. AstraZeneca's CEO Pascal Soriot said an interview on September 10 it is normal for vaccine trials to be paused due to unexpected events, but that "the difference is with other vaccine trials is that the whole world is not watching them."

Meanwhile, European regulators are set to announce a review of AstraZeneca's vaccine as soon as this week, according to a source familiar with the matter, per Bloomberg.  The head of the European Medicines Agency, Marco Cavaleri, said in July the agency would announce "rolling reviews" of potential coronavirus vaccines after the summer, adding that the EU could approve the first effective vaccine by the end of this year. A rolling review avoids delays, allowing a quick approval of a drug from the European Commission, which is necessary in emergencies like a pandemic. Shares in AstraZeneca rose 1% in early London trading on Wednesday.

AstraZeneca should still know by year-end whether its experimental vaccine protects people against coronavirus, as long as it is cleared to resume trials soon, its chief executive said on Thursday amid doubts over its rollout. Governments desperate to put an end to the COVID-19 pandemic which has caused more than 900,000 deaths and huge economic and social disruption during 2020 are pinning their hopes on a vaccine. However British drugmaker AstraZeneca suspended late-stage trials on its potential vaccine this week after an illness in a participant in Britain who was reported to be suffering from symptoms associated with transverse myelitis, a rare spinal inflammatory disorder. The World Health Organization (WHO) has flagged the AstraZeneca vaccine, which is being developed with the University of Oxford, as the most promising for coronavirus.

CEO Pascal Soriot said during an online event on Thursday that AstraZeneca (AZN.L) did not yet know the diagnosis of the participant who was ill, adding that it was not clear if the volunteer had transverse myelitis and more tests were needed. The diagnosis would be submitted to an independent safety committee and this would usually then say whether trials can be resumed, Soriot said, adding it was usual for such pauses. “It’s very common, actually, and many experts will tell you this,” Soriot said, adding: “The difference with other vaccine trials is, the whole world is not watching them, of course. They stop, they study, and they restart.” Shares in AstraZeneca fell on Wednesday after the trial halt raised doubts about the timeline for the vaccine’s rollout.

AstraZeneca would supply vaccines to countries at the same time to ensure a fair and equitable distribution, Soriot said, reiterating that the company was close to having capacity to produce 3 billion doses at sites set up around the world to prevent governments from restricting distribution. With up to 60,000 people set to participate in the study program, AstraZeneca’s CEO said the volume was typical of vaccine trials and large enough to spot rare side effects. “With this you are going to pick up very rare events.” he said, adding that a planned staggered launch, prioritizing at-risk groups, would provide further assurance for the masses that are set to be covered by government plans at a later stage. Serum Institute of India, one of AstraZeneca’s (AZN.L) development and production partners, said on Thursday it was joining the suspension, backtracking on remarks that it did not face any issues.

Transverse myelitis cases after a vaccination have been documented before, but concrete links between the condition and vaccinations have not been established, experts said. The U.S.-based Mayo Clinic concludes that the association so far is not strong enough to warrant limiting any vaccine. A 2009 review in the journal Lupus of nearly 40 years of English-language publications found 37 cases of transverse myelitis associated with hepatitis B vaccines, measles-mumps-rubella, diphtheria-tetanus-pertussis and others.  The vaccines remained on the market, Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said. Linking such an autoimmune response to a single factor like a vaccine is problematic, he said, given the number of immunological, hormonal or environmental factors at play. “It’s terribly difficult to be sure,” Evans said. 

RBC Capital Markets analyst Bryan Abrahams cautioned the trial participant’s condition must be thoroughly investigated. “Even a single case could possibly imply a rate or association higher in the study than what is normally observed sporadically” he wrote to investors, adding a one in 10,000 risk, if confirmed, would likely be unacceptable. BioNTech (BNTX.O), among the frontrunners in the vaccine race with partner Pfizer (PFE.N), echoed remarks by Soriot that clinical halts are a common feature of immunization trials. 

“Safety is a top priority,” its CEO Ugur Sahin told Reuters.

Experts are concerned that the company has not been more forthcoming about two participants who became seriously ill after getting its experimental vaccine. AstraZeneca revealed details of its large coronavirus vaccine trials on Saturday, the third in a wave of rare disclosures by drug companies under pressure to be more transparent about how they are testing products that are the world’s best hope for ending the pandemic. Polls are finding Americans increasingly wary of accepting a coronavirus vaccine. And scientists inside and outside the government are worried that regulators, pressured by the president for results before Election Day on Nov. 3, might release an unproven or unsafe vaccine. “The release of these protocols seems to reflect some public pressure to do so,” said Natalie Dean, a biostatistician and expert in clinical trial design for vaccines at the University of Florida. “This is an unprecedented situation, and public confidence is such a huge part of the success of this endeavor.” Experts have been particularly concerned about AstraZeneca’s vaccine trials, which began in April in Britain, because of the company’s refusal to provide details about serious neurological illnesses in two participants, both women, who received its experimental vaccine in Britain. Those cases spurred the company to halt its trials twice, the second time earlier this month. The studies have resumed in Britain, Brazil, India and South Africa, but are still on pause in the U.S. About 18,000 people worldwide have received AstraZeneca’s vaccine so far.

AstraZeneca’s 111-page trial blueprint, known as a protocol, states that its goal is a vaccine with 50 percent effectiveness — the same threshold that the Food and Drug Administration has set in its guidance for coronavirus vaccines. To determine with statistical confidence whether the company has met that target, there will have to be 150 people ill with confirmed coronavirus among participants who were vaccinated or received placebo shots. However, the plan anticipates that a safety board will perform an early analysis after there have been just 75 cases. If the vaccine is 50 percent effective at that point, it might be possible for the company to stop the trial early and apply for authorization from the government to release the vaccine for emergency use. In allowing only one such interim analysis, AstraZeneca’s plan is more rigorous than the others that have been released, from Moderna and Pfizer, Dr. Eric Topol, a clinical trials expert at Scripps Research in San Diego, said in an interview. Moderna allows two such analyses, and Pfizer four. He said the problem with looking at the data too many times, after a relatively small number of cases, is that it increases the odds of finding an appearance of safety and efficacy that might not hold up. Stopping trials early can also increase the risk of missing rare side effects that could be significant once the vaccine is given to millions of people. Dr. Topol said AstraZeneca’s plan, like those of Moderna and Pfizer, had a problematic feature: All count relatively mild cases of Covid-19 when measuring efficacy, which may hamper efforts to determine whether the vaccine prevents moderate or severe illness.

Such plans are not usually shared with the public “due to the importance of maintaining confidentiality and integrity of trials,” Michele Meixell, a spokeswoman for AstraZeneca, said in a statement. The company has released few details about the two cases of serious illness in its trial. The first participant received one dose of the vaccine before developing inflammation of the spinal cord, known as transverse myelitis, according to a participant information sheet for AstraZeneca’s vaccine from July. The condition can cause weakness in the arms and legs, paralysis, pain and bowel and bladder problems. The case prompted a pause in AstraZeneca’s vaccine trials to allow for a safety review by independent experts. A company spokeswoman told the Times last week that the volunteer was later determined to have a previously undiagnosed case of multiple sclerosis, unrelated to the vaccine, and that the trial resumed shortly thereafter. Transverse myelitis can sometimes be the first sign of multiple sclerosis, which involves more complex symptoms. But the myelitis alone can also occur after the body encounters an infectious agent like a virus. The company said it had not confirmed a diagnosis in the second case, a participant who got sick after the second dose of the vaccine. A person familiar with the situation who spoke with The Times on the condition of anonymity said the participant’s illness had been pinpointed as transverse myelitis. The trial was paused again on Sept. 6 after she fell ill. The condition is rare, but serious, and experts said that finding even one case among thousands of trial participants could be a red flag. Multiple confirmed cases, they said, could be enough to halt AstraZeneca’s vaccine bid entirely...

Pharmaceutical company AstraZeneca said it was pausing late-stage global trials. The race to develop a coronavirus vaccine careened into a speed bump Tuesday when the U.K.-based pharmaceutical company AstraZeneca announced it was pausing late-stage global trials of its leading vaccine candidate after one of the trial’s volunteers experienced a serious suspected adverse reaction. The company signed a deal to manufacture and distribute a vaccine developed at Oxford University and had hoped that the vaccine would be ready and available by the end of the year. The company announced it was voluntarily pausing its vaccine to investigate whether or not the illness in the volunteer was linked to the vaccine. For the Trump administration, which has badly mishandled the U.S. response to the pandemic, the near-singular focus now rests on producing an effective vaccine as fast as possible that could potentially let the country resume some semblance of normal daily life. President Donald Trump has played fast and loose with COVID cures of all sorts over the last six months and, never being one to let reality get in the way of what serves him best, caused concern over the sanity and safety of the well-established trial process.

The Trump administration has been considering fast-tracking the AstraZeneca vaccine, bypassing normal regulatory standards so that the president could have some good news to announce before Americans go to the polls on Nov. 3. “To speed up the process, the drugmaker has begun manufacturing the jab before the trials are complete or the vaccine is approved,” the Financial Times reports. “The partnership—which has received more than $1 billion in funding from the U.S. Biomedical Advanced Research and Development Authority—has agreed to deliver more than 300 million doses to the U.S. government.” In a statement, AstraZeneca described the decision to halt the trial as a “routine action” that “has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials.” “A person familiar with the situation, who spoke on the condition of anonymity, said that the participant who experienced the suspected adverse reaction had been enrolled in a Phase 2/3 trial based in the United Kingdom,” according to the New York Times. “The individual also said that a volunteer in the U.K. trial had received a diagnosis of transverse myelitis, an inflammatory syndrome that affects the spinal cord and is often sparked by viral infections. However, the timing of this diagnosis, and whether it was directly linked to AstraZeneca’s vaccine, is still unknown.”