Novavax ÍøÒ×ÌåÓý vaccine the first to demonstrate clinical efficacy against South African variant

28 January 2021 - Wits University

Clinical efficacy demonstrated in Phase 2b South Africa trial.

Wits-VIDA is the lead institution in the Novavax ÍøÒ×ÌåÓý vaccine trial in South Africa, which today announced results of the SA phase 2b and the UK phase 3 trials. 

• Clinical efficacy demonstrated in Phase 2b South Africa trial with over 90% of sequenced cases attributable to prevalent South Africa escape variant
• Strong efficacy in Phase 3 UK trial with over 50% of cases attributable to the now-predominant UK variant and the remainder attributable to ÍøÒ×ÌåÓý virus

The Novavax vaccine, known as NVX-CoV2373, is the first vaccine to demonstrate not only high clinical efficacy against the prototype SARS-CoV-2, but also significant clinical efficacy against both the rapidly emerging South African (501Y.V2 variant) and UK mutant (N501Y) variants.

In the South Africa Phase 2b clinical trial, 60% efficacy for the prevention of mild, moderate and severe ÍøÒ×ÌåÓý disease was observed in the 94% of the study population that was HIV negative. The trial also achieved its primary efficacy endpoint in the overall trial population, including HIV positive and HIV negative subjects, showing efficacy of 49.4%.

¡°The higher efficacy of the vaccine in the UK than in South Africa is because the variants circulating in SA are less sensitive to vaccine induced immune responses. Nevertheless, the 60% reduced risk against ÍøÒ×ÌåÓý illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the only COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,¡± says Professor Shabir Madhi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax ÍøÒ×ÌåÓý vaccine trial in South Africa.¡°The public health value of vaccines extends beyond a simple point estimate. The ability of ÍøÒ×ÌåÓý vaccines to impact the pandemic will depend on the product, its efficacy, and how quickly we can scale up coverage of the vaccine eventually.¡± 

ÍøÒ×ÌåÓý the South African Novavax ÍøÒ×ÌåÓý vaccine phase 2b trial results

In the South Africa Phase 2b clinical trial, 60% efficacy (95% CI: 19.9 ¨C 80.1) for the prevention of mild, moderate and severe ÍøÒ×ÌåÓý disease was observed in the 94% of the study population that was HIV-negative.  Twenty-nine cases were observed in the placebo group and 15 in the vaccine group.  One severe case occurred in the placebo group and all other cases were mild or moderate. The clinical trial also achieved its primary efficacy endpoint in the overall trial population, including HIV-positive and HIV-negative subjects (efficacy of 49.4%; 95% CI: 6.1 ¨C 72.8).

This study enrolled over 4,400 patients beginning in August 2020, with ÍøÒ×ÌåÓý cases counted from September through mid-January. During this time, the triple mutant variant, which contains three critical mutations in the receptor binding domain (RBD) and multiple mutations outside the RBD, was widely circulating in South Africa. Preliminary sequencing data is available for 27 of 44 ÍøÒ×ÌåÓý events; of these, 92.6% (25 out of 27 cases) were the South Africa escape variant. 

Importantly in this trial, approximately 1/3 of the patients enrolled (but not included in the primary analyses described above) were seropositive, demonstrating prior COVID-19 infection at baseline.  Based on temporal epidemiology data in the region, the pre-trial infections are thought to have been caused by the original COVID-19 strain (i.e., non-variant), while the subsequent infections during the study were largely variant virus.  These data suggest that prior infection with COVID-19 may not completely protect against subsequent infection by the South Africa escape variant, however, vaccination with NVX-CoV2373 provided significant protection. 

¡°The 60% reduced risk against ÍøÒ×ÌåÓý illness in vaccinated individuals in South Africans underscores the value of this vaccine to prevent illness from the highly worrisome variant currently circulating in South Africa, and which is spreading globally. This is the first ÍøÒ×ÌåÓý vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,¡± says Professor Shabir Maddi, Executive Director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the Novavax ÍøÒ×ÌåÓý vaccine trial in South Africa. ¡°I am encouraged to see that Novavax plans to immediately begin clinical development on a vaccine specifically targeted to the variant, which together with the current vaccine is likely to form the cornerstone of the fight against ÍøÒ×ÌåÓý.¡±

Novavax initiated development of new constructs against the emerging strains in early January and expects to select ideal candidates for a booster and/or combination bivalent vaccine for the new strains in the coming days. The company plans to initiate clinical testing of these new vaccines in the second quarter of this year.

¡°A primary benefit of our adjuvanted platform is that it 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 of COVID-19,¡± said Gregory M. Glenn, M.D., President of Research and Development, Novavax. ¡°Combined with the safety profile that has been observed in our studies to-date with our COVID-19 vaccine, as well as prior studies in influenza, we are optimistic about our ability to rapidly adapt to evolving conditions.¡±

The Coalition for Epidemic Preparedness Innovations (CEPI) funded the manufacturing of doses of NVX-CoV2373 for this Phase 2b clinical trial, which was supported in part by a $15 million grant from the Bill & Melinda Gates Foundation.

ÍøÒ×ÌåÓý the UK Novavax ÍøÒ×ÌåÓý vaccine phase 3 trial results

The study enrolled more than 15,000 participants between 18-84 years of age, including 27% over the age of 65. The primary endpoint of the UK Phase 3 clinical trial is based on the first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) ÍøÒ×ÌåÓý with onset at least 7 days after the second study vaccination in serologically negative (to SARS-CoV-2) adult participants at baseline.

The first interim analysis is based on 62 cases, of which 56 cases of ÍøÒ×ÌåÓý were observed in the placebo group versus 6 cases observed in the NVX-CoV2373 group, resulting in a point estimate of vaccine efficacy of 89.3% (95% CI: 75.2 ¨C 95.4).  Of the 62 cases, 61 were mild or moderate, and 1 was severe (in placebo group). 

Preliminary analysis indicates that the UK variant strain that was increasingly prevalent was detected in over 50% of the PCR-confirmed symptomatic cases (32 UK variant, 24 non-variant, 6 unknown).  Based on PCR performed on strains from 56 of the 62 cases, efficacy by strain was calculated to be 95.6% against the original ÍøÒ×ÌåÓý strain and 85.6% against the UK variant strain [post hoc].

The interim analysis included a preliminary review of the safety database, which showed that severe, serious, and medically attended adverse events occurred at low levels and were balanced between vaccine and placebo groups.

ÍøÒ×ÌåÓý the Novavax vaccine known as NVX-CoV2373

NVX-CoV2373 is a protein-based vaccine candidate engineered from the genetic sequence of SARS-CoV-2, the virus that causes COVID-19 disease. NVX-CoV2373 was created using Novavax¡¯ recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and is adjuvanted with Novavax¡¯ patented saponin-based Matrix-M? to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigen and can neither replicate, nor can it cause COVID-19. Over 37,000 participants have participated to date across four different clinical studies in five countries.  NVX-CoV2373 is currently being evaluated in two pivotal Phase 3 trials: a trial in the U.K that completed enrollment in November and the PREVENT-19 trial in the U.S. and Mexico that began in December.