6 crucial unanswered questions about AstraZeneca's coronavirus vaccine results

  • For the third consecutive Monday, a drugmaker said its coronavirus vaccine candidate was successful in late-stage studies.
  • AstraZeneca and the University of Oxford said their two-dose shot was effective at preventing COVID-19, according to preliminary results. 
  • AstraZeneca's news follows similar announcements of success from Pfizer and Moderna. Experimental COVID-19 shots from those drugmakers appeared to be 95% effective in preventing COVID-19, according to the companies.
  • While there are unanswered questions about all these programs, AstraZeneca's press release left a lot more to learn about its vaccine. 
  • Here are the six key questions we still have about the vaccine.
  • For more stories like this, sign up here for Business Insider's daily healthcare newsletter.

AstraZeneca said Monday that the experimental coronavirus shot it developed with the University of Oxford was highly effective, based on preliminary results from multiple late-stage studies, marking the third consecutive week with positive vaccine news.

While this latest development appears to be good, the results are incomplete and there are potentially more caveats than previous announcements from Pfizer and Moderna.

Over the past couple weeks, Pfizer and Moderna both announced their coronavirus vaccines succeeded in large-scale studies that respectively enrolled more than 40,000 and 30,000 participants. Both companies said their shots were about 95% effective in preventing COVID-19, with studies also showing promising signs that they also prevent severe illness. 

All three vaccine frontrunners are still experimental. None of the programs have published late-stage results in a medical journal, and US regulators have yet to authorize any of the shots for emergency use, let alone full approval.

To make AstraZeneca's results even more complicated, depending on which groups of participants were included in this early analysis, the vaccine was either 90%, 70%, or 62% effective at preventing COVID-19.

And while there are some details available to clear up why that's the case, unanswered questions begin to pile up quickly without more specifics.

Here are six burning questions still facing AstraZeneca's vaccine program. 

Read more: Drugmakers behind 3 coronavirus vaccines say they work. Here's everything we know about the race for a vaccine and when you might be able to get a shot.

1. So how effective is it really? 

Let's start with what we learned on Monday about AstraZeneca's shot. 

AstraZeneca is running multiple late-stage trials across the globe. Monday's results came from pooling results from trials in the UK, South Africa, and Brazil, which include about 23,000 volunteers.

On average, getting two doses of the vaccine was 70% effective in preventing COVID-19, the company said. That's based on 131 cases of COVID-19 among trial participants, but AstraZeneca did not provide the exact breakdown of how many in the control group got sick versus those receiving the experimental shots.

Having that information matters more when considering the next detail the company included: the trials ended up testing different doses of the vaccine. 

This wasn't on purpose, but rather due to a dosing error that researchers, on balance, decided to roll with. Instead of having one active group that got two injections of the full-strength dose, a subgroup of participants received a half-strength dose followed by the full-strength. 

The subgroup of 2,741 people showed 90% effectiveness. But, all of a sudden, a massive trial hinges on less than 3,000 volunteers. Could additional data change this figure, either for better or worse?

Professor Andrew Pollard is the chief investigator of Oxford's global clinical trials, he was confident that the sample size is big enough with more data is being added. "It's a reasonable amount of the trial population – about a third of [trial participants] in the UK," he said at a press briefing on Monday.

"We've had a lot more data accumulating since [data collection] and we'll continue to do so," Pollard added. "So I think we'll have further information then in the weeks ahead that will improve the confidence in that result."

Among 8,895 participants who got both full-strength doses, the vaccine appeared to be just 62% effective in preventing COVID-19. 

62% may still be a positive —especially when regulators were looking for a vaccine that was more than 50% effective — but it's notably lower than the 95% results from Moderna and Pfizer.

2. What happens to the US-based trial? 

AstraZeneca is saying the vaccine's most effective if you get a half-strength dose initially followed by the full-strength injection. But only about 2,700 people in clinical trials have been given that regimen.

Will AstraZeneca be able to pivot ongoing research to further test that dosing plan and build more evidence? The company has a massive opportunity to do so with an ongoing US-based trial that seeks to recruit about 40,000 participants. 

The trial has recruited about 11,000 people so far in the US, and is currently only testing two full-strength doses of AstraZeneca's vaccine, which appeared to be 62% effective from these preliminary findings. 

"They may well decide to look at the low dose, standard dose, or they might decide to look at low dose, low dose," Associate Professor Katie Ewer, a senior immunologist involved in Oxford's research, told Business Insider. "So they will take this information into account I think and have a think about what they want to study going forward." 

Could this US trial be adapted to start testing a new dosing regimen, or is it too late to make such a drastic change to the protocol?

That will be a discussion to watch between AstraZeneca and US regulators. 

3. Does the shot reduce severe disease?

An ideal coronavirus vaccine wouldn't just prevent symptomatic disease but would specifically help reduce the chances of becoming critically ill. 

Pfizer and Moderna have both put forward preliminary data from their late-stage trials that show a promising trend for their vaccines.

Both immunizations appeared to significantly reduce the odds of getting seriously sick from COVID-19. Pfizer's study had 10 cases of severe illness, with nine in the placebo group and one in the vaccinated arm. Moderna's trial had 11 people get seriously ill, with all 11 happening in the placebo arm. 

At first glance, AstraZeneca's result appears to be similar good news. The press release touted that no participants who received the experimental shots had severe COVID-19.

Notably, instead of using a placebo to compare its results against, some of the trials used a meningitis vaccine as its control group.

That control group also had zero cases of severe COVID-19. It remains to be seen if the shot can actually outperform the control in preventing the worst outcomes of the disease. 

"It may just be chance that we just happen to not have any cases in the 20,000 people we've vaccinated, or it could just be that we're picking people up earlier when they get infected than the general population," Ewer said.  

Read more: How the pharma giant Pfizer teamed up with a little-known biotech to develop an effective coronavirus vaccine in record time

4. Could the vaccine prevent transmission and asymptomatic infection? 

It's unclear if getting AstraZeneca's vaccine lowered people's chances of getting infected and spreading the virus, particularly as an asymptomatic carrier. 

This is an unknown facing all the leading vaccine programs. In general, clinical studies are most powerful when designed to answer one question. In this case, that was preventing disease. 

Oxford scientists said Monday that the group getting AstraZeneca's vaccine had fewer asymptomatic infections. Researchers sent out weekly testing kits to all UK participants throughout the course of the study to test for a potential benefit on reducing infections. 

But the company has provided no detailed data to back that up. It's not yet clear if that finding was statistically significant, or if the trials will be rigorous and large enough to produce a definitive answer on that question. 

5. How safe is the vaccine? 

On Monday, AstraZeneca said "no serious safety events related to the vaccine have been confirmed."

SVB Leerink biotech analyst Geoffrey Porges called that description "hardly reassuring" in a note to investors.

"They did not disclose any information about any actual safety events," Porges added. 

AstraZeneca's program has been under heightened worries about its safety profile. 

All of its global trials were put on hold after an "unexplained illness" in an British trial participant. Studies eventually resumed, with US regulators taking nearly 50 days to agree it was safe to do so.

It still remains unclear what exactly happened with that participant, and what AstraZeneca shared Monday didn't clarify. That safety information will have to be submitted to regulators though, and the company will need to be able to persuade regulators there are no reasons for alarm.

Ewer, who was involved in the research, said they had "published all the data we have on safety so far", and wasn't aware of any other major safety concerns among trial participants. 

"There was the one that was reported a while ago that was investigated and that's resolved now," Ewer said. "As far as I know, there's nothing else."

Ewer added there are multiple journal articles on the vaccine's safety that will be published "probably this week." 

6. How long will the vaccine protect against COVID-19? 

However effective AstraZeneca's vaccine winds up being, a critical unknown is how long people will enjoy that protection. 

By attacking a brand-new virus, scientists simply do not know when, or if, protection from a vaccine will wane enough to leave people vulnerable to the coronavirus.

This unknown holds true for all coronavirus vaccine frontruners, including shots from Moderna and Pfizer.

The only way to know for sure will be long-term follow-up data these studies continue to collect.

Read more: How the sprint for a coronavirus vaccine transformed Moderna into a $39 billion powerhouse that's poised to reshape biotech

Digital Health Briefing

Healthcare Explained:

Telehealth Industry
Value-Based Care
Senior Care & Assisted Living Market
Medical Devices & Wearable Tech
AI in Healthcare
Remote Patient Monitoring

Do you have a personal experience with the coronavirus you’d like to share? Or a tip on how your town or community is handling the pandemic? Please email [email protected] and tell us your story.

Get the latest coronavirus business & economic impact analysis from Business Insider Intelligence on how COVID-19 is affecting industries.

Get the latest Pfizer stock price here.

Source: Read Full Article