EXPERT REACTION: Novavax vaccine shows 89.3% efficacy in phase 3 trial

The media release of phase 3 (UK) and 2b (South Africa) clinical trial results for the Novavax COVID-19 vaccine are encouraging but must be considered carefully. These results have not been subject to a peer review process and the reported vaccine efficacy of 89.3% (UK trial) only an estimate. Interim analysis was based on only 62 individuals however it is promising that COVID-19 transmission was significantly lower in those who received the vaccine compared with those that received only a placebo.

The emergence of the more virulent strains of COVID-19 during the UK clinical trial has been fortuitous for Novavax, providing evidence that the vaccine has efficacy against COVID-19 and UK and South African variants. This does not mean however that COVID-19 vaccines from Pfizer, Moderna or Oxford-AstraZeneca are less effective, only that currently clinical data is lacking to confirm efficacy against the variants.

Interim analysis provided in the media release for safety of the Novavax vaccine is rather ambiguous and reads “.. showed that severe, serious and medically attended adverse events occurred at low levels and were balanced between vaccine and placebo groups”. I am uncertain what Novavax considers a low level, exactly how many events were serious, and clarification required as to what is considered a balance between cohorts.

The news from Novavax is mixed. This is the first efficacy data we have seen from a protein-based vaccine. This is also the first evidence that clinical efficacy is reduced against the variants of concern that have arisen in the UK and South Africa. In the UK, it was 95% against the original SARS CoV 2 and 85% against the B117 UK variant. Overall this was 89%.

More worryingly, in South Africa, where the B1351 variant was dominant, it was only 60% effective, and as low as 49% when HIV infected people were included in the analysis. B1351 in South Africa and P1 in Brazil have two additional sites of mutation compared to the UK B117, so may be more resistant to vaccines, now confirmed by the Novavax data.

This means we urgently need to know the efficacy of other vaccines in the Australian plan, such as Astra Zeneca and Pfizer, against these variants, and plan accordingly.  They all target the same protein, so we can expect reduced efficacy to variant strains with these vaccines. These are likely to become the dominant strains globally and are more contagious, and the B117 appears to be more severe.

In Manaus, Brazil, the P1 variant, which has mutations in the same three regions as the South African variant, seems to be infecting people who were already infected in 2020, so it’s like a new pandemic. Meanwhile, our border control measures are more important than ever to mitigate the risk of variant strains causing an epidemic here.

Additionally, the data also tell us that we need high efficacy vaccines for immunosuppressed people, as they do not respond as well.

Overall this is another great result in terms of vaccine efficacy, and this provides evidence that we will have yet another viable alternative vaccine at our disposal in the near future.
 
It is not unexpected news that the efficacy of the vaccine seems to be lower against the new UK variant. However, even taking into account this finding, the efficacy is impressive.
 
The early results from South Africa are not as encouraging. However, it's important to temper the interpretation these early results with the fact that this data in South Africa is based on relatively small numbers as well as the characteristics of participants taking part in these trials having some unique features. So we need to wait for the full results to come in and scrutinise the data carefully before jumping to too many conclusions.
 
However, these results showed much lower efficacy and suggest that the vaccine is not as effective against the South African variant.
 
Based on first principles it was always going to be a distinct possibility that vaccines based on the spike protein for SARS-CoV-2 would be affected to some degree by a mutation in the spike protein that is occurring in the new variants. If there was a change in the effectiveness of the vaccine, the key question was always going to be to what degree the vaccine would be affected. That is, would this result in a minor reduction in the efficacy of the vaccine or a more substantial effect? This initial data from South Africa suggests that it may be having a substantial effect on the vaccine for the South African variant which is a real concern.

The latest results from the clinical trials of the Novavax COVID-19 vaccine are both promising, and at the same time a further indication that a new generation of COVID-19 vaccines will likely be required to combat emerging variants of the virus. 

Importantly, these trials have been performed during the emergence and rapid spread of new variants of the virus that causes COVID-19. The data therefore provides invaluable information on the efficacy of the vaccine against different SARS-CoV-2 variants in a real-world setting. 

The interim analysis of the phase 3 trial performed in the UK provides extremely encouraging results on the efficacy of the Novavax COVID-19 vaccine. The vaccine efficacy was found to be 95.6% against the original COVID-19 virus and 85.6% against the UK variant. This is strong protection from a vaccine that has already proven to be safe. 

A smaller Phase 2b trial carried out in South Africa was performed when the South Africa virus variant was widely circulating. Vaccine efficacy of just under 50% in this study is not as good as some of the other COVID-19 vaccines currently being distributed, but more concerning is that almost all of the COVID-19 cases detected in this study were caused by the B.1.351, or South Africa, variant. Novavax is wisely adjusting its vaccine formulation to specifically target the virus variant, with the aim of providing a greater protective effect against this rapidly spreading variant.

Reported results from the Novavax COVID-19 vaccine appear very promising. In principle, their approach is similar to that used in the development of the US influenza vaccine marketed as FLUBLOK, in which the influenza a c-DNA HA gene is inserted into baculoviruses which can then be grown to high titre in cultured insect cells.

Vaccine efficacy is further enhanced by the incorporation of a targeted adjuvant which could (although I am not certain about this) reduce effective antigen dose required. 

The great advantage of the vaccine is the apparent absence of any need for ultra-cold storage facilities.