Analysts assess fallout after AstraZeneca halts PhIII Covid-19 vaccine dosing to probe a possible serious adverse event
Investigators at AstraZeneca have ordered a halt to dosing their closely-watched Covid-19 vaccine in order to probe a potentially severe adverse event — reportedly involving inflammation of the spinal cord — suffered by one of the trial participants.
In a statement out Tuesday evening, a spokesman for the pharma giant told Endpoints News that the study had been put on hold to investigate an illness. Later Tuesday, they sent a revised statement, which noted that the halt is voluntary, not ordered by regulators. It reads:
As part of the ongoing randomised, controlled global trials of the Oxford coronavirus vaccine, our standard review process was triggered and we voluntarily paused vaccination to allow review of safety data by an independent committee. This is a routine action which has to happen whenever there is a potentially unexplained illness in one of the trials, while it is investigated, ensuring we maintain the integrity of the trials. In large trials illnesses will happen by chance but must be independently reviewed to check this carefully. We are working to expedite the review of the single event to minimise any potential impact on the trial timeline. We are committed to the safety of our participants and the highest standards of conduct in our trials.
The spokesman did not say what illness was involved, but the New York Times reported that the halt was triggered by a case in the UK of transverse myelitis, an inflammation of the spinal cord that can interrupt messages that spinal cord nerves transmit. According to Johns Hopkins, “it is characterized by symptoms and signs of neurologic dysfunction in motor and sensory tracts on both sides of the spinal cord.”
The condition can be triggered by a variety of things, including vaccinations.
AstraZeneca’s shares slid 6% after the bell on Tuesday, a sharp drop for a Big Pharma of that size. Shares of Moderna and BioNTech, the two mRNA leaders in Phase III, each jumped 5%.
This is the first such pause in the frenzied race to get a Covid-19 vaccine to the goal line. And the interruption on a Covid-19 leader like this triggered headlines worldwide. AstraZeneca, like the rest of the leading developers working on a pandemic vaccine, has been barreling ahead into late-stage pivotal work on a jab for the coronavirus that has disrupted the world. But at every quick step, execs at the multinational have also repeatedly assured all involved that they will not hesitate to slow things down if warranted.
The next big question is how long AstraZeneca’s vaccine could be on pause and whether there could be a spillover involving other vaccine makers.
Andrew Berens at SVB Leerink put it this way, sizing up the impact if it is transverse myelitis:
AZN’s vaccine study may be postponed by weeks to months, as the safety database is scrutinized and trial protocols revised. Further, this AE could have the potential to slow down vaccine development more broadly. Transverse myelitis has not been definitively linked to any commercial vaccines, but it has been shown to be related to natural virus infection, and a few cases of transverse myelitis were described after administration of the MMR, varicella, and hepatitis B vaccines (the mechanistic evidence was determined to be weak per the Institute of Medicine, currently the National Academy of Medicine).
Safety issues — particularly when they could be tied to a serious adverse event — loom particularly large here. Any suggestion of a safety problem could raise concerns for all involved, posing added problems in the event they provoke public resistance to a shot. And there are political implications as well. As President Trump has promised a vaccine by year’s end, or even sooner, the top vaccines have a shot at a snap OK. Safety issues would put a vaccine further behind in the line.
Jefferies’ Michael Yee was quick to pick up on that aspect, writing:
While we see this event as more of a short- to medium-term topic for debate, we do believe these vaccines will likely end up being differentiated on efficacy and safety in their Phase IIIs, which could drive opinions on which is “best” and eventual market uptake.
At our latest count, we include the AstraZeneca vaccine in 3rd place among 29 companies in or near the clinic, right behind the mRNA leaders at Pfizer/BioNTech and Moderna. They’ve been working with $1.2 billion in public financing for this work, with the Phase III getting underway in July. Investigators plan to recruit 30,000 patients in the US and 50,000 worldwide as they look for a broad patient group to test safety and efficacy.
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