Shares in AstraZeneca fell as much as 6% on Tuesday after the company confirmed that a phase 3 trial of its experimental COVID-19 vaccine AZD1222 has been put on hold due to a possible safety issue. AstraZeneca called the move “a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials,” but indicated it was trying to expedite the review to “minimise any potential impact on the trial timeline.”
According to a report in STAT News, the hold is due to a “suspected serious adverse reaction” in a participant in the UK, with sources suggesting that the person had developed transverse myelitis. The report also cited an individual familiar with the development as saying researchers were told the action was taken out of “an abundance of caution.” It is unclear how long the hold on the trial will last, although analysts at Shore Capital noted that “any suspension to the trial is likely to lead to delays in…timelines.”
The Phase III programme evaluating AZD1222, which is being co-developed with the University of Oxford, is looking to recruit a total of up to 50,000 participants globally with results expected later this year. AstraZeneca announced last week that it had kicked off a Phase III study in the US, while late-stage testing had already begun in the UK, Brazil and South Africa, with plans to expand to other countries. On Tuesday, Brazilian regulator Anvisa said that AstraZeneca informed it of the suspension of all global trials for the vaccine.
No safety signals in early testing
In July, interim data from a Phase I/II trial were published in The Lancet showing that the vaccine was well tolerated with no early safety concerns, and that it also triggered a robust immune response against SARS-CoV-2 in all evaluated participants. AstraZeneca suggested it is possible that the illness in the UK trial participant was not caused by the vaccine. “In large trials, illnesses will happen by chance, but must be independently reviewed to check this carefully,” the company said, adding that its action will help “[ensure] we maintain the integrity of the trials.”
Commenting on the news, Paul Offit, an infectious disease expert on the FDA’s vaccine advisory committee, noted that in the earlier study, more than half of people had fevers. “When you give it to hundreds of people that may be all you see. But if you start to give it to thousands or tens of thousands, there may be people with a more robust immune response,” he added.
Second pause of study
Meanwhile, UK Health Secretary Matt Hancock said “it’s not actually the first time this has happened to the Oxford vaccine,” in reference to an earlier pause of the Phase III study, which was quickly resolved. “It’s a standard process in clinical trials whenever they find something that they need to investigate,” Hancock added.
Analysts from Jefferies agreed that “temporary pauses in dosing of subjects is standard clinical trial practice,” adding “given the expedited path into Phase III (trials)…we believe it is not surprising a serious adverse event triggered a study halt to investigate if drug-related.” Bloomberg Intelligence analyst Sam Fazeli said “with much hope based on early trials, the halt to that of AstraZeneca’s COVID-19 vaccine shows the perils of rushing to market. The side effect may have nothing to do with the vaccine, but could slow recruitment into its trials if they are restarted, and those of others.”
Earlier on Tuesday, AstraZeneca CEO Pascal Soriot was among a group of nine pharmaceutical chief executives to issue a joint pledge to “uphold the integrity of the scientific process” in developing vaccines for the novel coronavirus. The other drugmakers who signed on are BioNTech, GlaxoSmithKline, Johnson & Johnson, Merck & Co., Moderna, Novavax, Pfizer and Sanofi. The statement sought to reassure the public amid speculation of political pressure on the FDA to authorise a COVID-19 vaccine as soon as possible.