After enduring months of public criticism over its COVID-19 vaccine, AstraZeneca PLC finally caught a moment of reprieve this week when U.S. trial data showed the shot to be highly effective — working well in older people, and raising no safety concerns.
The good news lasted less than a day.
A group of experts meant to work hand in hand with the drugmaker on its trial safety contacted U.S. government agencies late Monday to express concern. The results made public just hours earlier may be outdated, they said, in a stunning departure from protocol. Astra promised up-to-date numbers in the next 48 hours.
The late-night volley from the National Institute of Allergy and Infectious Diseases appeared to blindside the company, which took almost 12 hours to come back with a public message. The twist is the latest in a string of unexpected turns — from communication blunders to reports of alarming side effects — that started last year and have dogged Astra’s vaccine, a potentially key weapon to help large parts of the world combat the pandemic.
The U.S. agency was questioning the efficacy data released by Astra. This gave the vaccine a reading of 79%, but the U.S. body complained that it gave an “incomplete” view because the data cut off on Feb. 17, more than a month before the study was made public.
The Washington Post reported Tuesday that federal health officials wrote in a letter to AstraZeneca that if the full trial data had been accounted for, the vaccine’s efficacy would have been between 69% and 74%.
Whether the inclusion of later data might lower the efficacy has been left unanswered for the time being, and that’s created yet another layer of uncertainty for a drug already grappling with dwindling public support following a series of public gaffes.
While safety panels can sometimes clash with investigators, it typically plays out behind closed doors, according to Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene & Tropical Medicine.
“It is usually done in private, so this is unprecedented,” said Evans.
Astra has committed to providing its COVID-19 vaccine at cost during the pandemic, but with multiple variants raising the prospect of annual vaccinations, like the flu, the company may have the chance to cash-in on its efforts at some point. If the vaccine continues to stumble, affecting public take-up, it could impact that ambition and future revenue stream.
Astra’s vaccine woes started last year when the company paused global trials after a U.K. volunteer suffered a neurological condition. Whether or not the symptoms were linked to the vaccine couldn’t be determined, and the U.K. trial resumed days later — but U.S. authorities declined to restart the study there for almost seven weeks. That delay set the vaccine back months behind U.S. rivals Pfizer Inc. and Moderna Inc.
In November, results from Astra and partner Oxford University’s trials in the U.K. and Brazil brought more confusion than clarity after the study produced two different efficacy numbers. The trial also failed to include enough elderly people to establish efficacy for a crucial patient group considered most at risk of severe COVID-19.
The handling of those early results and the trial pauses unsettled scientists and investors, hurting the vaccine’s credibility.
It also gave rise to tensions with the U.S. and forced the company to wait for the results from its U.S. trial to apply for clearance for the shot from the Food and Drug Administration.
The first national approvals brought no further clarity. When the U.K. regulator backed the vaccine at the end of December, it endorsed two full shots as much as 12 weeks apart — an interval that had shown promising results — while picking the dosing levels that had demonstrated weaker results in the clinical trial.
The ruling led to a debate among governments about how far injections could be spaced out without threatening protection of the largest-possible population.
The lack of data about the elderly further muddied the picture after the European Union cleared the vaccine for all adults in January: at least 10 EU countries broke ranks and endorsed it only for younger patients.
Many have since reversed course as more data from real-world use showed the shot works for everyone, turning the Astra vaccine into the backbone of a successful U.K. campaign.
But comments from politicians in the interim — French President Emmanuel Macron called the shot “quasi-ineffective” for older citizens, and German Health Minister Jens Spahn said people who got the vaccine would be able to get a different one later if there were enough supplies — further eroded faith in the product, which became perceived publicly as an inferior choice.
Then came the supply showdown with the EU. Astra first told lawmakers about delivery constraints in late January, creating a two-month standoff where the 27-nation bloc partly blamed the Cambridge, England-based company’s delays for the sluggish vaccination campaign. The spat has since escalated, with the EU threatening to block Astra’s exports if it doesn’t honor contractual obligations.
Chief Executive Officer Pascal Soriot has sought to defend his company’s handling of the shots, particularly over supply constraints, pointing to the complexities of mass-producing a vaccine just a year after the novel coronavirus was declared a pandemic.
But AstraZeneca’s multiple missteps have made it a liability to immunization efforts, said Michael Kinch, a drug development expert and associate vice chancellor at Washington University in St. Louis. Such events only risk giving fodder to anti-vaccine crusaders, and create doubts in the minds of the hesitant, he said.
Further compounding the vaccine’s woes was a hasty suspension last week by more than a dozen countries to investigate side-effects that might include lethal blood clots. While regulators have said the shot’s benefits outweigh its risks, some countries have yet to reinstate inoculation programs with the Astra vaccine.
The problem with this week’s U.S. study results may be a symptom of the wider pressure that Astra is feeling over its vaccine.
The company hadn’t planned to publish its initial analysis, opting instead to wait for the full set of data. But the concerns in Europe over safety and effectiveness in older people led the drugmaker to share the details sooner.
It’s unclear how this latest issue might affect the shot getting U.S. approval. Astra was expecting to get FDA clearance early next month.
But with the U.S. having already inoculated more than 100 million people and Astra’s product proving no more effective than some other shots already in circulation, the vaccine might struggle to establish itself in a crowded field.
If the U.S. were short of vaccine, Astra’s prospects would be better, but as shots appear plentiful now, approving AstraZeneca’s could just be harmful, said Kinch.
“I’m as pro-vaccine as you get,” said Kinch, author of “Between Hope and Fear: A History of Vaccines and Human Immunity.”
“I don’t think we should approve this vaccine, and it’s purely out of principle.”
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