Novavax confirms efficacy against emerging coronavirus variants

The interim results from one arm of Novavax’s phase 3 clinical trials show it has 95.6% efficacy against the main coronavirus strain – and is almost as effective against the concerning UK variant, at 85.6%.
 
The news comes as a welcome potential boost to global vaccination efforts as the EU and US scramble to secure scarce supplies of the Pfizer/BioNTech and Oxford University/AstraZeneca vaccines.  
 
Delays to Australia’s vaccination rollout are now likely, with the Federal Government indicating manufacturing-related shortages could push back the start date for phase 1a, which was originally due to begin in the second week of February.
 
However, local production of the Oxford University/AstraZeneca vaccine remains on track, with Australian manufacturer CSL reporting the first doses will become available from March. GPs will be heavily involved in the distribution of this vaccine, and more than 1000 general practices have already expressed interest in participating from phase 1b onwards.
 
But despite Novavax’s positive results from the UK, phase 2b clinical trials in South Africa found its candidate only possessed around 60% efficacy against the 501.v2 variant in HIV-negative participants, which dropped to just below 50% when including HIV positive participants.
 
The 501.v2 variant, which like the UK variant is much more contagious than the main coronavirus strain, accounted for more than 90% of cases of the virus found in the trial. Experts have suggested this variant has mutations that are likely to make vaccine-derived immune responses less effective, while some South African participants also contracted the new variant despite already having been infected by the original strain.
 
In response, vaccine makers such as Moderna and Novavax are focusing on these variants of concern in updated vaccines.
 
Regardless, Professor Terry Nolan, Head of the Vaccine and Immunisation Research Group at the Doherty Institute, told newsGP the new Novavax results are broadly very positive.
 
He said the reduced effectiveness against the South African variant appears to be in line with recent in vitro neutralisation studies, which suggested this variant could affect vaccine targeting. A similarly worrying Brazilian variant also has mutations in the same regions as the South African one.
 
‘The South African variant has three key mutations in the receptor-binding domain, compared to just one in the UK variant,’ Professor Nolan said. ‘This is what matters; the receptor-binding domain is where it attaches to the cell.
 
‘Even though it appears to have dropped in efficacy, it’s still in the acceptable range; 50% or greater effectiveness is good enough.
 
‘We’d prefer in the 90s, but we need at least 50%. The [new variant] has shaved efficacy a bit, but hasn’t rendered the vaccine useless.’
 
The fact the recombinant protein vaccine is still mostly effective against dangerous new variants is a relief, according to Associate Professor Paul Griffin, who ran the Australian arm of the Novavax phase 1/2 trial last year.
 
‘There was an expectation that the current vaccines would be effective against variants, but to see it in clinical trial data is reassuring,’ he told newsGP.
 
‘Australia is in a good position. It’s likely we’ll end up with three vaccines on different platforms and with slightly complementary properties.
 
‘If Novavax proves safe and effective and gets registered, it should be easier to use and overcome logistical challenges seen with the Pfizer vaccine.’ 
 
The Novavax approach is expected to allow rapid production which could – if approved by regulators – help address emerging vaccine shortfalls as the EU and US scramble for doses. 


Associate Professor Paul Griffin is relieved Novavax’s candidate has so far proved effective against new COVID variants.
 
In the EU, AstraZeneca and Pfizer have flagged their delivery volumes may be lower than expected due to manufacturing issues, while the US rollout is also going slower than expected.
 
These shortages are likely to affect Australia, with Department of Health (DoH) secretary Professor Brendan Murphy telling a Senate select COVID-19 committee hearing on Thursday that the target date for reaching four million vaccinations has been extended into April due to supply-chain concerns.
 
AstraZeneca market access director Alice Morgan told the same hearing that 1.2 million international doses of her company’s vaccine – flagged for the second round of vaccinations – are on track to arrive in Australia by March, though this could change due to the ‘fluid situation’.
 
But local production of 50 million doses of AstraZeneca vaccines by CSL should be unaffected, she said.
 
More broadly, Professor Nolan said Novavax’s results are important because they demonstrate efficacy from a different vaccine platform to those that have already been approved.
 
‘This is the first result from a recombinant protein vaccine candidate,’ he said. ‘We’ve seen results from three platforms – mRNA, viral vector, and now recombinant proteins. All three are yielding highly effective vaccine candidates.’
 
Crucially, Professor Nolan also said the Novavax approach is ‘scalable to massive dimensions’ and that it would be possible to produce hundreds of millions of doses ‘relatively quickly’.
 
Burnet Institute visiting fellow Emeritus Professor Greg Tannock said the Novavax results ‘appeared very promising’ and noted the approach is similar to the development of the FLUBLOK flu vaccine, which achieves faster production than traditional egg-based manufacturing methods.
 
Governments are facing a shifting terrain of data about the new vaccines, with a key advisory body in Germany recommending against the AstraZeneca vaccine for people aged over 65 due to a lack of data.
 
German newspapers have reported this vaccine has an efficacy of less than 10% among the over-65 cohort, but these claims have been strongly challenged by AstraZeneca.
 
La Trobe University epidemiologist Associate Professor Hassan Vally believes the incorrect reporting seems to have been based on a misunderstanding.
 
‘The reason we have a lower certainty in the estimate of vaccine efficacy for those over 65 years is simply that the numbers who received the vaccines in these trials were much smaller than for the younger age groups,’ he said.
 
Associate Professor Griffin said the main issue appears to be a ‘slight lack of supportive data’ rather than any safety concerns with the AstraZeneca candidate.
 
‘It looks like a great vaccine but they haven’t necessarily conducted the trials optimally,’ he said. ‘They are doing a great job of addressing these concerns.’ 
 
Some participants in AstraZeneca vaccine clinical trials were mistakenly given a half dose, which triggered a better immune response than the full dose.
 
While Novavax is yet to have a vaccine registered, it received $1.6 billion in funding from Operation Warp Speed, the US Government’s effort to accelerate vaccine creation.
 
The company is currently recruiting for a large phase 3 trial in the US and Mexico, with a goal of enrolling at least 25% of all volunteers who are 65 years old or older. It is not known when these results will become available.
 
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