In the crisis of the coronavirus that clings to the world, all eyes are on every bump and piercing the path to the end of the pandemic. So, of course, the news that the researchers triggered a standard stop in the clinical trials of a leading candidate in the COVID-19 vaccine turned out to be fast and alarming headlines on Tuesday.
The global phase III trials for the AZD1222 vaccine (formerly ChAdOx1) —developed by the University of Oxford and drug giant AstraZeneca — have been put on a “temporary” and “voluntary” pause for a “ standard review process, “AstraZeneca said in a statement Wednesday
According to the company, the pause was triggered by a “possibly unexplained illness” in one of the thousands of participants involved in its trials. For each standard protocol, researchers should pause the test to investigate whether the disease is related to exposure to the experimental vaccine or not.
“In large clinical trials, diseases occur inadvertently and should be independently evaluated,” the statement reads. “AstraZeneca is working to expedite single event analysis to minimize any potential impact on the test timeline.”
Since the news broke, experts have been in a hurry to emphasize that such pauses are routine and common in the final clinical trials. If so, it is a positive sign that proper safety monitoring and investigations are taking place. Among the experts was leading infectious disease researcher Anthony Fauci, who, in an interview Wednesday morning on CBS News, said pause was “not uncommon.”
“We see it in general, in almost everyone,” Drs. Fauci. “But you do not know until you investigate it—[if] it is an unpleasant event associated with something else that only happened during the time the clinical trial began, ”or from the real vaccine.
Fauci explained that, per standard protocol, when unexplained diseases appear, it is common to pause the test, investigate the disease, and see if there are any, other similar diseases or problems that have increased, under of radar, to any other test participant.
“I think it’s important to point out that that’s why you have different stages of trials, to determine if, in fact, these candidates are safe,” Fauci said. At this stage, it is an example of the kinds of things you do to make sure vaccines are safe, he said.
Commitment at the beginning
Of the hundreds of COVID-19 vaccine candidates in development, AZD1222 is seen as one of the most promising candidates for an effective pandemic coronavirus vaccine. It is also one of the farthest development partners, starting with phase II / III clinical trials in the UK, Brazil, and South Africa earlier this summer and a 30,000-year trial in the US last month. Tests are also set for Japan and Russia.
The vaccine is a viral-vector-based vaccine. That is, it packaged a bit of the pandemic coronavirus, SARS-CoV-2, inside another, harmless virus that was delivered to the immune system. The harmless virus in this case is an adenovirus that causes mild infections in chimpanzees and is further engineered so that it cannot reproduce in human cells. This adenovirus carries the SARS-CoV-2 spike protein, which is critical for infection and is thought to stimulate strong, protective immune responses.
In early animal tests, AZD1222 protected monkeys from developing pneumonia after exposure to SARS-CoV-2. And in an early clinical trial involving 1,077 people, AZD1222 provoked potential protective immune responses and appeared to be generally safe. Researchers say that mild side effects – including pain, fever, chills, muscle aches, headaches, and illness – are common. But no serious side effects have been reported.
AstraZeneca has become so severe in pain that it has paused in current trials, STAT news first reported. An anonymous source first told STAT only that the disease had occurred to a UK participant and the man was expected to recover.
The news quickly spread that the disease could be transverse myelitis, though, first reported from an anonymous source in The New York Times. Transverse myelitis is inflammation of the spinal cord that can be triggered by many conditions, including inflammatory systemic diseases (such as multiple sclerosis), vascular diseases, and infections from bacteria, viruses, parasites, or fungi . In rare cases, it can be triggered from a vaccine. AstraZeneca declined to confirm any of those details by the sick participant. In a statement to the Times, the company said “the event is being investigated by an independent committee and it is too early to conclude a specific diagnosis.”
But in a private conference call with investors Wednesday, AstraZeneca CEO Pascal Soriot confirmed that a UK woman, who received the vaccine (not a placebo), had neurological symptoms associated with transverse myelitis , according to a STAT follow-up story. Soriot said he was improving and was expected to be released from the hospital early Wednesday.
According to the National Institutes of Health, transverse myelitis often causes weakness of the feet, pain, sensory changes (numbness and rupture), and bowel and bladder defecation. Approximately 1,400 people in the United States are newly diagnosed each year. There is no cure, but it can be cured with corticosteroids, other medications, and physical therapies. Most people do at least a partial recovery, but some are left with moderate disabilities, such as walking problems, nervous sensitivity, and bladder and intestinal problems.
Interestingly, Soriot also mentioned in the call to these investors that this is really the second time the trial has been suspended. It also seems to have been paused in July after a participant showed neurological symptoms and was later diagnosed with multiple sclerosis. The researchers concluded that the tests were not related to the vaccine.
It is unclear if the new UK female disease is similarly unrelated. So far, little can be gained from pausing other than AstraZeneca following standard safety procedures — a point Soriot emphasized.
“At AstraZeneca we put science, safety and social interests at the heart of our work,” Soriot said in a statement. “This temporary pause is living proof that we adhere to those principles as a single event on one of our test sites is reviewed by a committee of independent experts. This committee will guide us when trials may be resumed, so that we can continue our work as soon as possible to provide this vaccine widely, evenly and without profit during this pandemic. “