Virus World

A large, United Kingdom-based Phase 2/3 study testing a Covid-19 vaccine being developed by AstraZeneca has been restarted, according to a statement from the company. News that the trial is resuming comes four days after the disclosure that it had been paused because of a suspected serious adverse reaction in a participant.  A spokesperson for AstraZeneca told STAT that at this point, only the trial in the U.K. has been resumed. The company is also conducting Phase 2/3 or Phase 3 trials in the U.S., Brazil, and South Africa.  “The Company will continue to work with health authorities across the world and be guided as to when other clinical trials can resume to provide the vaccine broadly, equitably and at no profit during this pandemic,” the spokesperson, Michele Meixell, wrote in an email.

Saturday’s statement from AstraZeneca said the independent U.K. investigation into the event has concluded and it advised the Medicines Health Regulatory Authority, Britain’s equivalent of the Food and Drug Administration, that it was safe to resume the trial. The MHRA concurred and gave the green light for the trial to restart. The illness that triggered the international pause, which occurred in a woman who was in the vaccine arm of the U.K. trial, has not been officially disclosed, though AstraZeneca CEO Pascal Soriot told a group of investors on Wednesday that her symptoms were consistent with transverse myelitis, a serious condition involving inflammation of the spinal cord that can cause muscle weakness, paralysis, pain and bladder problems. The AstraZeneca statement said information about the illness the woman suffered cannot be disclosed. Oxford University, where the vaccine was developed, said in a separate statement that the nature of the illness cannot be revealed “for reasons of participant confidentiality.” As part of the review process, independent boards overseeing trials of a number of other Covid-19 vaccines were analyzing their own data, looking for cases. There are at least 35 vaccines in clinical trials around the world, nine of which are in Phase 3, the final stage of testing.

It’s not uncommon for clinical trials to be paused. This is the second known hold of studies of the AstraZeneca vaccine. A woman in the U.K. trial was diagnosed with multiple sclerosis in July, but that event, which triggered the first pause, was deemed not to be related to the vaccine. An AstraZeneca spokesperson previously described the decision as a “routine action which has to happen whenever there is a potentially unexplained illness” in a trial. Still, the pause drew extraordinary attention because of the urgent need for progress on Covid-19 vaccines in the midst of the pandemic.

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.