A phase III trial of AZD-1222, an experimental coronavirus vaccine developed by Astrazeneca plc and Oxford University, has been paused due to an unexplained illness that occurred in the U.K., the company said on Sept. 8.
The unexpected news landed shortly after Astrazeneca CEO Pascal Soriot signed on to an industry pledge to "always make the safety and well-being of vaccinated individuals our top priority," now supported by the executives of nine industry leaders in COVID-19 vaccines development. Soriot renewed the vow Wednesday, saying that Astrazeneca will be guided by a committee of independent experts on when the trials could restart, “so that we can continue our work at the earliest opportunity to provide this vaccine broadly, equitably and at no profit during this pandemic.”
Details of the hold and its potential impact remained scarce on Wednesday. But a participant information sheet for a phase II/III study of the vaccine, sometimes called ChAdOx1-nCov-19, notes at least one adverse event. The sheet, with a version date of July 12, notes that while neither allergic reactions nor Guillain-Barré syndrome had been seen in the study, “one volunteer in the trials of ChAdOx1 nCoV-19 developed symptoms of transverse myelitis (inflammation in the spinal cord), which has not required medical treatment and is being investigated, though the cause is uncertain.”
U.S. NIH Director Francis Collins appeared to allude to that event during a Senate Health, Education, Labor and Pensions (HELP) Committee hearing on Wednesday. “To have a clinical hold, as has been placed on Astrazeneca as of yesterday because of a single serious adverse event is not at all unprecedented,” he said. “With an abundance of caution, at a time like this, you put a clinical hold, you investigate carefully to see if anyone else who got that vaccine, or any other vaccines, might have had a similar finding of a spinal cord problem.”
In late July, Astrazeneca posted interim data from AZD-1222’s phase I/II blinded, multicenter, randomized, controlled clinical trial of 1,077 healthy adults showing the vaccine was tolerated and generated a robust immune response against the virus. The data showed a fourfold increase in antibodies to the virus spike protein in 95% of the patients a month after injection. A T-cell response, peaking by day 14, was also induced and maintained for two months afterward.
Albany Molecular Research Inc. (AMRI), of Albany, N.Y., recently signed a supply agreement with Astrazeneca to support the manufacture of the adenovirus vector-based candidate. AMRI will be responsible for the sterile fill and finish at its drug product manufacturing facility in Albuquerque, N.M. The facility’s cGMP manufacturing capacity could potentially produce millions of doses of AZD-1222 annually, AMRI said.
The Serum Institute of India Pvt. Co. Ltd., the world’s largest vaccine manufacturer in volume terms, is also preparing to manufacture the vaccine. It has entered a $150 million agreement with Gavi, the Vaccine Alliance, and the Bill & Melinda Gates Foundation to initially produce up to 100 million doses of the Jenner Institute-developed vaccine. Oxford Biomedica plc, of Oxford, U.K., has signed a supply agreement with Astrazeneca for the vaccine, too.
Analyst reaction to news of the clinical hold spanned the spectrum from minimization to deeper worry. JP Morgan’s Cory Kasimov advised clients to “keep calm and carry on,” while at the same time expressing some concern about how the development “could damage the public perception of vaccine safety.”
SVB Leerink analyst Geoffrey Porges was less sanguine, writing that the adverse disclosed “is the worst kind for vaccine developers – rare, severe, complex in presentation, difficult to diagnose, and plausibly associated with the vaccine technology. Resolving this question, and proving the negative, could take months for this program, and has implications for the development strategy (but not the development risk) for all the other COVID vaccines in pivotal trials.”
Astrazeneca did not respond to a request for further information on Wednesday. American depository shares in the company (NYSE:AZN) fell $1.07 to close at $53.64.