Novavax shares gained as much as 26% on Thursday after the company said its protein-based COVID-19 vaccine candidate NVX-CoV2373 met the primary endpoint of a Phase III trial in the UK, demonstrating an efficacy rate of over 89%, with high protection also seen against the fast-spreading UK variant. However, in a separate Phase IIb study conducted in South Africa that included people infected with an "escape mutant" version of SARS-CoV-2 first identified in that country, the vaccine turned out to be less than 50% effective.
The company indicated that it has been developing new constructs against the emerging variants since early January and expects to select ideal candidates for a booster and/or combination bivalent vaccine for the new strains "in the coming days." It plans to start clinical testing of these new vaccines in the second quarter.
The UK study enrolled more than 15,000 participants between 18 to 84 years, including 27% who were over the age of 65. The primary endpoint looked at the first occurrence of PCR-confirmed symptomatic COVID-19 with onset at least seven days after the second dose in participants who were serologically negative to SARS-CoV-2 at baseline.
The first interim analysis is based on 62 cases of COVID-19, with six cases observed in the NVX-CoV2373 group and 56 among those who were given placebo, translating to vaccine efficacy of 89.3%. Sixty-one of the cases were characterised as mild or moderate, while one subject in the placebo arm developed severe COVID-19. Novavax noted that the now-predominant UK variant, dubbed B.1.1.7, was detected in 32 of the cases, versus 24 non-variant infections and six cases where the strain was unknown. Based on testing performed on these 56 cases, the efficacy of NVX-CoV2373 was calculated to be 95.6% against the original non-mutated COVID-19 strain and 85.6% against the UK variant.
Meanwhile, Novavax said a preliminary review of the safety database revealed that severe, serious, and medically attended adverse events occurred at "low levels and were balanced between vaccine and placebo groups." The company said it initiated a rolling submission to the UK's Medicines and Healthcare products Regulatory Agency (MHRA) in mid-January.
The South African trial enrolled over 4400 patients, with COVID-19 cases counted from September through mid-January, during which time another variant, known as B.1.351/501Y.V2, began circulating widely in the country. Preliminary sequencing data were available for 27 of 44 COVID-19 cases, and 25 turned out to have been infected with this new variant, which has shown evidence of being less susceptible to previous antibodies.
However, Novavax said the study still achieved its primary efficacy endpoint in the overall trial population, including HIV-positive and HIV-negative subjects, demonstrating effectiveness of 49.4% against COVID-19. That number rose to 60% when HIV-positive patients were not included. Specifically, there were 15 cases of COVID-19 in the vaccinated group and 29 in the placebo arm, which had the only instance of severe illness, while all the rest were mild or moderate.
"We now have a vaccine, the first vaccine that's shown efficacy not only in the prototype COVID-19 original strain, but in two variant strains, one in the UK [and] one in South Africa," remarked CEO Stanley Erck, adding "it's the only data that shows we can get efficacy against all three." Gregory Glenn, who heads R&D, said Novavax's adjuvanted platform "uses a very small amount of antigen, enabling the rapid creation and large-scale production of combination vaccine candidates that could potentially address multiple circulating strains…We are optimistic about our ability to rapidly adapt to evolving conditions."
Earlier this week, Moderna said it was weighing different strategies on how to combat emerging mutations of SARS-CoV-2, including developing an updated version of its vaccine mRNA-1273 that would be protective against the South African strain. The company noted that sera from people vaccinated with mRNA-1273 showed a six-fold reduction in response to B.1.351, although this was still deemed strong enough to give some protection, while the UK variant was neutralised just as efficiently as the unmutated strain.
Meanwhile, Novavax said it would also provide the new data to the FDA, which could lead to potential emergency-use authorisation in the US by April, although it is possible the agency may hold off on deciding on the vaccine until they see results from the late-stage PREVENT-19 trial currently under way in the US and Mexico. That study has enrolled 16,000 people, toward a target of 30,000, and Novavax suggested that an initial readout could be available by the end of March.
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