- Vaccinations in studies of AstraZeneca and the University of Oxford's experimental coronavirus shot are on hold after an unexplained illness in one participant triggered a safety review, the British drugmaker confirmed to BioPharma Dive. The trial pause was first reported by STAT.
- AstraZeneca acted on its own to stop testing, the company said in a statement, but provided little other information about the adverse event. Such safety reviews are a standard part of clinical testing and it's not yet clear whether the illness was directly attributable to vaccination, nor how long a hold might last.
- The pause in vaccinations applies to all studies of AstraZeneca and Oxford's vaccine, including the large Phase 3 trial began last week in the U.S. The suspected adverse reaction occurred in an individual enrolled in the partner's U.K. study, AstraZeneca confirmed.
So far, there have been few setbacks in an extraordinary worldwide push to develop a coronavirus vaccine in record time. But developers' speed has also brought fears potential side effects might be missed in testing, a concern AstraZeneca and other leading drugmakers have recently sought to ease by committing to thoroughly conduct high-quality trials.
The trial pause and safety review, which brought AstraZeneca shares down Wednesday morning, is a sign of that commitment, as the drugmaker and its partners at Oxford are under immense pressure to move quickly.
Their shot is among the most advanced globally, one of just a handful to be advanced into Phase 3 trials. Its status as a frontrunner, and AstraZeneca's preparations to ready large-scale production, have put the vaccine at the center of politicians' efforts to quickly clear a vaccine for their citizens.
Recent reports, for instance, indicated the Trump administration is considering fast-tracking a vaccine — potentially AstraZeneca and Oxford's — for emergency authorization before the U.S. election in November.
Early clinical studies showed the vaccine to be generally safe, causing chills, fatigue, fever and headache that were mostly mild to moderate in nature and treatable with aspirin.
But researchers are watching closely for rarer, more serious side effects. The mid-stage study of some 10,000 volunteers in the U.K., as well as the Phase 3 trial launched in the U.S. last week, are crucial precisely for this reason, as some adverse reactions might not show up until a vaccine is tested in tens of thousands of people.
"In large trials illnesses will happen by chance but must be independently reviewed to check this carefully," AstraZeneca said in a statement. "We are working to expedite the review of the single event to minimize any potential impact on the trial timeline."
A patient information sheet for the U.K. trial indicated one study volunteer had previously developed neurological symptoms, leading to an earlier safety review. The individual was subsequently diagnosed with an "unrelated neurological illness," according to the sheet, which was last updated in August.
It's not clear whether this person is the same as the one referred to by AstraZeneca in its decision this week to pause vaccinations.
The New York Times separately reported a participant in the U.K. trial had been diagnosed with transverse myelitis, an inflammation of the spinal cord that can damage the protective coating for nerve cell fibers. The report, which cited an unnamed source, did not specify when that diagnosis occurred nor whether it was linked to vaccination. Transverse myelitis can be caused by viral infections.
Geoffrey Porges, an analyst at SVB Leerink, wrote in an note to investors that this type of adverse reaction is "the worst kind for vaccine developers — rare, severe, complex in presentation, difficult to diagnose, and plausibly associated with the vaccine technology."
In an email, a spokesperson for AstraZeneca said "it is too early to conclude the specific diagnosis," adding that the event is under investigation by an independent committee.
Resolving the questions around this type of event could take weeks or even months, Porges noted.
AstraZeneca and Oxford's shot is a newer type of vaccine that uses a modified virus to deliver genetic instructions to train the body's immune system to fight off a pathogen. While well established in scientific circles, only two so-called viral vector vaccines have made it through to an approval, both for Ebola virus.
The partners had hoped the shot would be potent enough to give only once, but are now exploring a two-shot regimen.
In addition to AstraZeneca and Oxford, Johnson & Johnson, CanSino Biologics and Merck & Co. are also studying viral vector vaccines for the new coronavirus. Those trials could receive additional scrutiny in light of AstraZeneca's trial pause, Porges noted.
AstraZeneca and Oxford use a modified chimpanzee virus for their vaccine, while the others are using a modified adenovirus.
Editor's note: This story has been updated to include analyst comment, new information from clinical trial materials and an updated statement from AstraZeneca.