Government regulators in the United Kingdom have ordered Cambridge-based pharma AstraZeneca to pause development of its novel-coronavirus vaccine candidate after a patient in the U.K. apparently had an unspecified adverse reaction to the vaccine.
According to the U.S. Department of Health and Human Services, the stand-down order came from the U.K. Data Safety Monitoring Board, which oversees pharmaceutical trials. The U.K. board coordinated with American regulators in making its decision, HHS stated.
A “standard review process triggered a pause to vaccination to allow review of safety data,” a spokesperson for AstraZeneca told Statnews.
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It’s unclear exactly when AstraZeneca halted its trials and how long the freeze might last, but it’s worth noting that the company began enrolling the first test subjects for large-scale Phase 3 trials in the U.S. just eight days ago. The Phase 3 trials were set to involve 30,000 people in the U.S. plus around 10,000 others in the U.K.
AstraZeneca is developing its vaccine, known as “AZD1222,” along with Oxford University. It’s one of six vaccine candidates that have received major funding from Operation Warp Speed—and one of eight vaccines that have entered Phase 3 trials worldwide.
Moncef Slaoui, the chief adviser to Operation Warp Speed, the U.S. government’s $13-billion vaccine-accelerator, said the halt is proof that the vaccine development process is functioning as intended. “This pause while the adverse event is fully investigated means the science-based, data-driven process is working as it should,” Slaoui told The Daily Beast in a statement.
Operation Warp Speed is supporting a variety of different vaccine-candidates. A genetically-engineered “messenger RNA” vaccine from Massachusetts-based pharma Moderna is widely considered the leading candidate. Moderna began Phase 3 trials in late July.
Jennifer Reich, a sociologist at the University of Colorado Denver specializing in vaccination, echoed Slaoui’s sentiment that AstraZeneca’s trials-pause is a good sign. “In my experience and in terms of trust, moments like these can provide assurance to some that data systems to rigorously monitor safety are working and are catching possible risks,” Reich said.
But Keith Jerome, a University of Washington virologist, was less sanguine. “It’s hard to know how big a deal this is until we get more details on the reaction and how the participant is doing now,” he said.
And Jeffrey Klausner, a professor of medicine and public health at UCLA who previously worked at the U.S. Centers for Disease Control and Preventions, also expressed concern. “Already having a stopping event after only eight days of enrollment is worrisome,” he told The Daily Beast.
The pause underscores the difficulty the pharmaceutical industry and its government boosters face in their crash effort to quickly develop and deploy a coronavirus vaccine. It is also a reminder of the risk a faulty vaccine could pose to the health of potentially millions of people.
For all the recent advancements in vaccine technology, inducing immunity in people still involves injecting them with portions of some genetically-engineered or natural pathogen and hoping that the body responds with antibodies and T-cells, all without also making patients too sick.
“The reality of the vaccine development process is that there are lots of participants, and people have health issues that arise from time to time,” Jerome said.
AZD1222 is a so-called “non-replicating viral-vector adenovirus vaccine.” It includes a harmless-to-humans adenovirus taken from chimpanzees. Scientists engineered the adenovirus, versions of which can cause cold-like symptoms, to include a spike protein like that on the SARS-CoV-2 pathogen.
The theory is that the human immune system will recognize the protein and produce neutralizing antibodies to prevent infection by the actual novel coronavirus.
That theory held early on. AZD1222 produced an immune-response in a small number of test subjects during Phase 2 trials involving around 1,100 patients in the U.K. between April and June, according to a study that appeared in the science journal The Lancet in late July.
AstraZeneca’s testers split the 1,077 test subjects into two roughly equal-sized groups. One group got a meningitis vaccine. The other got a single dose of AZD1222. The scientists reported no significant adverse reactions from the test subjects during these early trials.
The researchers drew blood from 35 of the more than 500 subjects who received AZD1222 and tested the samples for antibodies and pathogen-destroying T-cells. All 35 had neutralizing antibodies and T-cells.
But Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, questioned why AstraZeneca only tested 35 people for antibodies. “What about those other 500 people?” he asked. “It looks a little sloppy, frankly.”
Although Offit challenged AstraZeneca’s thoroughness in the earlier trials, he declined to speculate about the seriousness of the Phase 3 pause. “We'll know when the company figures out whether the serious adverse event was causally, or only temporally, related to the vaccine,” he said.
Slaoui for one expressed confidence that, despite the AstraZeneca freeze, at least one vaccine would be ready for widespread use by the end of the year. Operation Warp Speed “is still on track,” he stated.
Of course, the first vaccine to get approval from the U.S. Food and Drug Administration might not be AstraZeneca’s. “The big thing now is to understand whether this was related to the vaccine, and if so whether there’s a way to avoid similar problems in the future,” Jerome said.
