0128 Novavax Efficacy
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Product Development

Novavax data sets benchmark for protein vaccines, bolsters South African variant’s status as bigger risk to first-wave products

Jan 29, 2021 | 3:26 AM GMT

Novavax’s efficacy readout suggests protein vaccines against SARS-CoV-2 could rival leading modality mRNA, and provides more evidence that among the two most watched viral variants, the South African strain poses the bigger resistance threat for front-runner vaccines and therapies.

On Thursday, Novavax Inc. (NASDAQ:NVAX) announced its COVID-19 vaccine candidate NVX-CoV2373 showed 89.3% efficacy in a Phase III trial in the U.K. 

While the company is the seventh to disclose efficacy results for a COVID-19 vaccine, it is the first to do so for a protein-based candidate, and the first to capture how newly emerging variants impact protection. 

Among the more than 15,000 participants enrolled in the U.K. study, there were 62 cases of symptomatic disease, 56 of which came from the placebo group, and six from the treatment group.

Thirty two of the cases in the interim analysis were caused by the B.1.1.7 (501Y.V1) variant traced to the U.K. 

A post-hoc analysis showed the vaccine’s efficacy was 85.6% for this strain, compared with 95.6% for the original SARS-CoV-2 strain; the latter rivals the performance of mRNA vaccines, whose trials read out before the U.K. variant is thought to have emerged.

The company also shared interim data from its South African Phase IIb trial, providing a snapshot of the vaccine’s performance against the  B.1.351 (501Y.V2) variant first identified in the country.

Here, the vaccine’s overall efficacy was 60% in HIV-negative subjects, with 29 cases in the placebo group and 15 in the vaccine group. HIV-negative participants made up 94% of the analyzed study population; when HIV-positive participants were included, the overall efficacy was 49.4%.

The company had viral sequencing data available for 27 out of 44 of the total cases observed in the trial, which showed 25 (92.6%) of these were caused by the South African variant. 

Novavax’s data linking the South African variant to a bigger drop in vaccine efficacy than the U.K. variant is the latest and most clinically relevant sign that the former is more resistant to products designed to target the original strain’s spike protein.

Studies assessing the variants’ effects on the viral neutralization potency of anti-spike therapeutic mAbs or serum from individuals vaccinated with mRNA vaccines Comiranty or Moderna COVID-19 Vaccine have also indicated the South African variant will be a bigger problem.

The South African strain has three mutations in the spike protein’s receptor binding domain (RBD), believed to be key for viral entry into host cells, while the U.K. variant carries only one of the three. The former also carries more mutations in the protein’s extracellular N-terminal domain.

A third variant traced to Brazil, B.1.1.28 (501Y.V3), has the same RBD mutations as the South African strain, and a similar effect on neutralizing antibody potency in viral culture studies.

NVX-CoV2373 is a recombinant protein nanoparticle vaccine against a full-length, prefusion stabilized version of the SARS-CoV-2 spike protein, delivered in combination with the company’s saponin-based Matrix-M adjuvant.

The company has initiated a rolling submission to MHRA, and believes it will have a final analysis in the next few weeks and submit a full data package to the agency within the next two to three months.

In early January, Novavax began developing new vaccine constructs targeting emerging variants. The company said it plans to select a candidate “in the coming days,” and initiate clinical testing of the vaccine next quarter; the new product could be deployed as a booster shot, or in combination with the original vaccine.

While protein is considered to be at a disadvantage to mRNA in terms of the time required to adapt and scale up a next-generation product, President of R&D Gregory Glenn said in a statement that the small amount of protein antigen required by the company’s platform enables “the rapid creation and large-scale production of combination vaccine candidates.”

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