Max Nisen and Sam Fazeli, who cover the pharmaceutical industry for Bloomberg Opinion and Bloomberg Intelligence, answered questions about Covid-19 vaccine trial data released early Monday by AstraZeneca Plc and the University of Oxford. The dialog has been edited and condensed.
Astra and Oxford on Monday became the third Covid-19 vaccine developers to announce positive early results from a large trial. But the findings don’t seem as straightforward or uniformly encouraging as those released by Pfizer Inc.-BioNTech SE and Moderna Inc. What should we make of them?
Max Nisen: The headline number — an average of 70% protection against Covid-19 disease — is positive but less impressive than the more than 90% efficacy seen from Moderna Inc. and the partnership between Pfizer and BioNTech. The data is also more confusing. The researchers disclosed data on two different dosing regimens: a half dose followed by a full dose resulted in 90% efficacy, while two full doses showed 62%.
Sam Fazeli: To my mind, the question really is what is the true efficacy of this vaccine? Why is there a group of subjects in whom the vaccine achieves 90% efficacy and another group that gets 62%? Also, the 90% level came from a group one-quarter the size of the one that hit 62%, so it’s the latter that you should believe in more from a statistical perspective. The company's explanation about dose levels is difficult to understand.
Max Nisen: That is a real concern. One possible explanation is this vaccine uses a different technology than Pfizer-BioNTech and Moderna. While theirs use messenger RNA to instruct cells to produce a coronavirus protein that prompts a protective immune response against Covid, Astra’s starts the process by using a harmless virus to insert a gene into cells. The body may react against that virus carrier, making it harder for it to get into cells and generate the right kind of immunity. So it’s possible that a full dose up front actually make the vaccine less effective by giving the body too much familiarity with the carrier virus.
Sam Fazeli: Yes, that would potentially explain it, but it creates some additional concerns. For one, a strong reaction to the viral carrier means it will be harder to reuse the vaccine because people will build immunity to the delivery mechanism. Astra could help answer these questions by providing data on how patients in both arms reacted to the carrier virus as well as more information from the seemingly more effective dosing regimen.
Max Nisen: Still, even with those caveats, the weaker regimen beats the FDA's 50% threshold for approval. There were also no cases of severe Covid or hospitalizations on the vaccine arm. And it's worth noting other points of differentiation with the mRNA vaccines. AstraZeneca has agreed to sell the vaccine at cost, so each dose is a few dollars. The Pfizer-BioNTech and Moderna vaccines both cost much more, and early supply has been snapped up by richer countries. The Astra vaccine is also much easier to store, which adds to the cost-based appeal for low-income nations. And because of ambitious manufacturing partnerships and the fact that mRNA is a newer technology, there will be many more doses of the Astra shot available. At the end of the day, we'll need to vaccinate the whole world, and broad vaccination with a less effective shot beats having to wait while the others are used very narrowly. Bottom line, there's still a role for this vaccine to fight the pandemic, right?
Sam Fazeli: Absolutely. There is nothing wrong with a vaccine that has 70% efficacy, especially in a world that needs as many doses as it can get. And it’s much easier to ship this vaccine around the world than either Moderna’s or Pfizer-BioNTech's vaccines. But the lower efficacy does mean that the many countries that will be relying on this vaccine will need to get a higher percentage of their populations inoculated to achieve the same level of broad protection as nations that will be using the mRNA shots. It is also possible that the Astra vaccine could be used for the time being, but then followed by a booster from other vaccines. One great thing that Astra is doing in its trial and Pfizer-BioNTech and Moderna aren’t is to collect swabs from all participants on a weekly basis, and not just those exhibiting symptoms. This can help address an important question: Does the vaccine stop the virus from spreading, in addition to stopping the development of disease? Once we see this data, the fortunes of Astra's vaccine could suddenly change.
Max Nisen: This all raises questions about who gets what vaccine and how the world will make those decisions, especially now that the Astra-Oxford effort has introduced more variety in the data. Many countries have already signed contracts with different vaccine manufacturers and will decide individually how to use the doses they get. There is also some effort toward international cooperation, like the COVAX Facility — an effort by several nonprofits and the World Health Organization to ensure access for developing nations. But in the absence of a single unified process or good comparative data on different vaccines, and given limited early supplies, things could be a bit chaotic. Any thoughts on how this is likely to play out?
Sam Fazeli: Indeed, this is what I always worry about. What if we get vaccines with differing upfront efficacy? Or worse, vaccines that have different durability or have varying effects on how well an infection can be controlled? I don't think we have enough data yet to make a decision on this from a longer-term perspective. My concern, though, is that if Astra's efficacy does not improve, it may impact people's interest in being vaccinated with that shot, which will work against the need for the high inoculation rates that are needed to reach herd immunity.
Max Nisen: That would be concerning. But at least for now, as I see it, the Astra data suggests its vaccine will be another useful tool in the pandemic fight, even if it comes with questions. We should get more data in the coming days and weeks, and I’m hopeful that it will provide more clarity and confidence.
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