Novavax announces high efficacy in phase 3 trials

American biotech company Novavax announced yesterday that their COVID-19 vaccine PREVENT-19 demonstrated 90% overall efficacy in its phase 3 trial, and provides 100% protection against moderate and severe disease.

The phase 3 trial showed PREVENT-19 had high efficacy (90.3%) against newer variants of concern and variants of interest (VOC and VOI respectively). This means that PREVENT-19 may be particularly useful in the ongoing fight against rapidly mutating variants, like those that have emerged in South Africa (Beta variant), the UK (Alpha) and India (Delta).

The phase 3 trial involved 29,960 participants from the US and Mexico, and showed high efficacy (91%) for higher risk populations, including over-65s and people with comorbidities.

What does high efficacy mean?

“Efficacy is a trial measure, and we get excited by anything that demonstrates at least 60 or 70% efficacy, because that means it works,” says Rob Grenfell, Health Director of the Health and Biosecurity department at CSIRO.

But, critically, efficacy is only a measure of comparison used within a trial – it can’t compare data from different trials because of the variability in structure and population demographics between them, as well as other variable factors like compliance to trial restrictions.

Grenfell says: “Let’s think about where the population that you tried it on was. What were the characteristics of that population? What was the level of circulating COVID virus to that population? What was the season that was enduring? What were the housing conditions of the people? There’s a lot of variability in this sort of setting.

“So, what you’re comparing inside the trial is you’re comparing people who’ve received the vaccine and people who have not received the active vaccine, so the placebo.”

Within that trial, everyone would have experienced nearly the same population conditions, and so can be accurately compared.

By contrast, effectiveness is a measure of how powerful a vaccine is in actually preventing a disease – or the severe effects of a disease – in the real world.

“That is what we’re now seeing reported on a regular basis from the UK,” says Grenfell. “They are probably the most forthcoming with publishing effectiveness data, that is; does it decrease the number of people being hospitalised or dying from the virus?

“This has been the one of the big challenges for the general public, I think; the research sector has been looking at efficacy, but the general public has not been introduced to this concept.”

According to Grenfell, comparing the efficacy and effectiveness of different vaccines will only become possible when researchers are able to conduct meta-analyses, combing through data from all the vaccine trials and rollouts.

Nonetheless, he says: “90% efficacy is fantastic.” Even more promising, he adds, is the high efficacy against variants – which are popping up with regularity around the globe.

How is PREVENT-19 different to other vaccines?

PREVENT-19 is a recombinant protein nanoparticle vaccine. This means it’s essentially made up of a genetically engineered protein that’s identical to the spike protein on the COVID-19 virus, and other proteins that give it structure. This spike protein triggers the body’s immune response when injected, and incurs immunity to the actual virus.

By contrast, the AstraZeneca vaccine is a typical viral vector vaccine, which means it contains a harmless virus that enters the body’s cells, delivers a piece of code that allows the body to create the protein of the COVID-19 virus, so the immune system learns to recognise COVID-19’s spike protein and produces an immune response.

Then there are mRNA vaccines like Pfizer and Moderna. mRNA vaccines deliver mRNA (genetic code) into the body, which contains the blueprint for how to make a spike protein. The body’s cells can then reproduce this protein, recognise it as foreign, and produce an immune response to it, which will be replicated in the event of encountering the real COVID-19 virus.

In terms of efficacy, AstraZeneca’s phase 3 trials showed 79% overall efficacy, while Pfizer and Moderna showed 95% and 94.1% respectively overall, but as previously highlighted, comparisons between trial efficacy cannot be drawn comfortably because of variability among trials.

Will it be rolled out in Australia?

In January, the Therapeutic Goods Administration (TGA) granted provisional determination to Australian pharmaceutical company Biocelect to apply for provisional registration for the Novavax PREVENT-19 vaccine in Australia. Within the Australian regulatory system, an Australian company is required to sponsor a foreign company to be registered in the country.

Given the apparent efficacy of PREVENT-19 against new variants, Grenfell says it’s not beyond the realm of possibility that Australians might get the Novavax vaccine as a booster.

“It’s quite clear with the wild behaviour of the virus globally that we will have more emergent variants of concern. And that next gen or a booster with a subsequent vaccine will be required probably six months after your first, and most certainly won’t be the same vaccine that you just had.

“That’s probably where Novavax, or even it’s been touted Moderna, may fit into that spectrum for us.”

Biocelect Director Jenny Herz says she expects the vaccine to become available to Australia in the last quarter of the year. She says the vaccine is particularly promising, not just because of its efficacy, but because Novavax already has the pre-existing import infrastructure and connections in the country.

“In the short term, it’s going to be imported, and that’s because the quickest way to get it here is actually to use the existing facilities that Novavax have already got up and running. But they certainly haven’t ruled out long term that there could be manufacturing in Australia.”

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Read more:

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• Mutations, variants and strains
• Equitable vaccine access for all