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AstraZeneca said Monday that its coronavirus vaccine reduced the risk of symptomatic Covid-19 by an average of 70.4%, according to an interim analysis of large Phase 3 trials conducted in the United Kingdom and Brazil.

The results, while positive, suggest the vaccine may be less effective than two others. Earlier this month, Moderna and the Pfizer and BioNTech consortium announced their messenger RNA, or mRNA, vaccines showed 95% efficacy against Covid-19 infections in their respective clinical trials.

Still, researchers at the University of Oxford, which partnered with AstraZeneca to develop the vaccine, hailed the latest data as promising.

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“The announcement today takes us another step closer to the time when we can use vaccines to bring an end to the devastation caused by SARS-CoV-2,” Sarah Gilbert, one of the co-developers of the vaccine, said in a statement.

The preliminary results on the AstraZeneca vaccine were based on a total of 131 Covid-19 cases in a study involving 11,363 participants. The findings were perplexing. Two full doses of the vaccine appeared to be only 62% effective at preventing disease, while a half dose, followed by a full dose, was about 90% effective. That latter analysis was conducted on a small subset of the study participants, only 2,741.

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A U.S.-based trial, being supported by Operation Warp Speed, is testing the two-full-dose regimen. That may soon change. AstraZeneca plans to explore adding the half dose-full dose regimen to its ongoing clinical trials in discussions with regulatory agencies, a spokesman told STAT in an email.

“We see a lot of merit in this regimen and we will now start discussions with regulators into incorporating this dose combination for further clinical investigation,’’ Brendan McEvoy said.

Why would less vaccine produce a better result?

“That’s a good question,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told STAT. Fauci suggested “there’s going to be a lot of hand waving” as people try to explain the results.

Fauci said it was possible the approach overrides a concern that exists about using two doses of a viral-vectored vaccine — the type AstraZeneca is developing. It uses an adenovirus that has been modified to include genetic material from the SARS-CoV-2 virus so that it introduces the immune system to the spike protein, which sits on the exterior of the virus.

Some experts had feared that if viral-vectored vaccines required a priming and then a boosting dose, the immune system might recognize the viral vector — in this case the adenovirus — and shut down the immune response before the vaccine has a chance to boost the response to the spike protein.

Fauci said the smaller initial dose may “tickle” the immune system enough to generate T cells, but not trigger development of antibodies that might work to suppress the response to the booster shot.

If a final analysis, conducted after the inclusion of additional data, concludes the vaccine’s actual efficacy is around 70%, that could be a problem.

“If it’s 70%, then we’ve got a dilemma,” said Fauci. “Because what are you going to do with the 70% when you’ve got two [vaccines] that are 95%? Who are you going to give a vaccine like that to?”

The problem was also flagged in an analysis by Geoffrey Porges of the investment bank Leerink. “We believe that this product will never be licensed in the US,” Porges wrote.

Fauci cautioned that full datasets — which the Oxford researchers said they intend to publish in a scientific journal — need to be pored over before conclusions can be drawn.

“We’ve got to look at the analyses, the real granular data. It’s always tough when you’re looking at a press release to figure out what’s going on,” Fauci said.

Other experts were more enthusiastic about the findings, suggesting the vaccine could be an important tool in low- and middle-income countries, where substantial production of the vaccine is expected to take place.

“The top line is this is more great news,” said Dave O’Connor, a vaccinologist at the University of Wisconsin-Madison, who is a volunteer in the AstraZeneca trial. (He believes he received the placebo, because he had no side effects after either dose.)

Beth Kirkpatrick, chair of the department of microbiology and molecular genetics at the University of Vermont, also saw good news.

“The AstraZeneca preliminary efficacy data are strong, but somewhat hard to compare to other vaccines due to variability in study design,” she said in an email. “Importantly, thus far, no volunteer who received this vaccine experienced severe Covid disease. This is great news, as is the initial suggestion that this vaccine might decrease asymptomatic infection.”

The Oxford researchers suggested the vaccine may reduce transmission of the virus, because they saw fewer asymptomatic cases in their trial. One of the challenges of controlling spread of the SARS-CoV-2 virus is that some people who become infected have no symptoms but can still transmit the virus.

There were no hospitalized or severe cases of Covid-19 reported in the studies. No serious safety events related to the vaccine occurred in the studies, AstraZeneca said.

Results from the U.S. trial will be delayed because that trial was paused for more than a month after one of the participants in the U.K. trial developed a rare but neurological condition, described as consistent with transverse myelitis. The Food and Drug Administration allowed the trial to resume in late October.

AstraZeneca said in a release that it intends to seek emergency use authorizations in countries around the world that have a regulatory framework that allows for conditional or early approval of medical products, and will seek an emergency use listing from the World Health Organization, a pathway to rapid approval for low-income countries.

The vaccine can be stored at normal refrigeration temperatures for up to six months, which will make it easier to deploy in more settings than the vaccines from Pfizer and Moderna, which must be stored at ultra-low temperatures. The Pfizer vaccine must be stored at -94 degrees Fahrenheit, while the Moderna must be stored at -4 F. Once thawed, Moderna’s vaccine can be stored at fridge temperature for a month.

“The vaccine’s simple supply chain and our no-profit pledge and commitment to broad, equitable and timely access means it will be affordable and globally available,” AstraZeneca CEO Pascal Soriot said in a statement.

AstraZeneca said it is on track to be able to produce 3 billion doses of its vaccine in 2021.

  • Flu shots have the same viral adenovirus vector, and this prior multiple exposure might render a Covid vaccine based on that same vector less effective. Has correllation between yearly flu shots and Covid vaccine efficacy been studied? As the flu shot content is guess work each year, and was only 25% effective last winter, even highly vaccinated people skip the (lousy) flu shot. Would these be the lucky ones who could have a better reaction to AZN’s adenovirus based Covid vaccine ? Does STAT news have any info to share on this potential and quite likely differential in vaccine efficacy ?

    • Flu shots do not use an adenovirus at all. They are virus raised in eggs and then killed and proteins from virus are purified- NA and HA protein. Some chicken protein remains. Not so with adenovirus based recombinant virus grown in human cell lines.

  • I am not a big fan of RNA vaccines, as I consider them suboptimal. But, I am even less of a fan of using other viruses as a carrier for wanted antigens. On the other hand, as long as they are good enough it is mostly an academic issue.

  • These findings suggest the Adenovirus vector induces immunity to itself, so that vector may not be an optimal platform for future vaccines in people who have already received an Adenovirus-based vaccine.

  • is it clear to anyone whether the phase 3 volunteers are receiving the half-dose regimen? my daughter is in the trial at UVM and we are hopeful that she got the vaccine but not so much if it’s only 62% effective. she enrolled because she has 3 chronic illnesses and she is the youngest participant in this trial. i also read on the AZ website that they were giving 33% of the participants the meningitis vax as the placebo dose followed by saline but had read differently elsewhere (ie. that the placebo would be saline for both doses). the vaccinologist who stated he thought he got a placebo makes me wonder how that could be bc i would assume both vaccines would cause a reaction. i am not educated in any of this, just trying to figure out if my kid got a vaccine and we can breathe a little easier. i know it’s a double blind study and no-one knows who got what till they un-blind it but i thought maybe someone commenting here might have some insight.

    • At present, the U.S. trial is not using the half dose, full dose regimen. Everyone is getting either 2 full doses or placebo, which in the U.S. trial is saline for both doses.

    • I suggest you go to Labcorp and get an anti-bodies test for your daughter. It’s $10 and will tell you if she got the actual vaccine. Whether or not she got the full or half dose may be known to you once there is EAU and unblinding.

  • Probably random statistical variation that caused the difference between the two regimes. 131 cases is not huge. The difference between the two regimes may hardly even be significant.

    • The dosage regimes should have been figured out in the phase I trial. Pfizer had 4 different targets going into Phase I, and chose the optimal one. Moderna had 3 dosage regimes, and again chose the optimal one. This trial in comparison is confusing because it has two dosage regimes and dramatically different results. 62% vs. 90% is a big difference. I suspect it may be because the first full dose of the adenovirus creates immune resistance to the adenovirus itself, that then negates the 2nd full dosage effects. This should have all been figured out in the Phase I trial.

  • This data is indeed strange. Perhaps they had a different definition of infection, or reviewed infections at a different point than Moderna and Pfizer. Or perhaps mRNA vaccines are better at triggering a targeted immune response to the spike protein. My understanding of this vaccine is that it’s based on mixing a primate virus with COVID, and maybe some of the ineffectiveness comes from taking that complicated, dare I say, antiquated step. This virus, at 70% effective, may be good enough for anyone worried about genetic side effects of the mRNA, but unless the mRNA vaccines prove less effective over time, it’ll probably all ship to the 3rd world while the American public prefers something that’s 95% effective.

    • Are viral vector vaccines that antiquated? A lot of reports on this vaccine are stating that it is 90% effective and it is hard to believe that AZ/OX will continue with the regimen that offers 62% efficacy. It is also worth pointing out that of the twelve thousand people who took this vaccine, none were hospitalised with Covid. AZ/OX have also reported that there is some evidence that their vaccine stops asymptomatic transmission although research continues on this. Perhaps all will become clearer once data comes in from the other countries taking part in the programme.

    • The Adenovirus vaccine is more stable, so it may be preferable to ship that to places where -70C freezers are not available. Also, I am still not convinced that there are no unforeseen effects of mRNA vaccines – and not only genetic effects.

    • As I understand it, the measurement of “infections” is, indeed, different in this trial than in Pfizer or Moderna’s. It looks to me like AZ swabbed participants regularly and is reporting all detected positives, whereas Pfizer & Moderna tested only those who became symptomatic.

      If that is the case, the AZ is detecting infections that would have gone uncounted in the Pfizer & Moderna trials, and so they might turn out to be similarly efficacious. Remember AZ reports no hospitalizations or serious cases in vaccine recipients, which is about the same as Pfizer & Moderna.

      And until we have better data, I’m not convinced the efficacy difference between the two dosage arms of the AZ trial is as large as initially reported. The small n of the half/full regimen leads to a large confidence interval around that 90% efficacy number.

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