Gaithersburg, Maryland headquartered Novavax has initiated a rolling submission for the two-dose protein-based vaccine to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) this month.
It has also started developing new constructs against the South African strain and expects to select ideal candidates for further development into either a booster and/or combination bivalent vaccine in the coming days. Clinical testing of these new vaccines will follow in the second quarter of this year.
UK Phase 3 trial results
More than 50% of the COVID-19 cases observed in the strong Phase 3 UK trial for NVX-CoV2373 came from the now-predominant UK variant. The study enrolled more than 15,000 participants between 18-84 years of age, with 27% of these over the age of 65.
The first interim analysis is based on 62 COVID-19 cases, of which 56 cases were observed in the placebo group and six cases were observed in the NVX-CoV2373 group, resulting in a point estimate of vaccine efficacy of 89.3% (95% CI: 75.2 – 95.4). Of the 62 cases, 61 were mild or moderate, with one severe case in the placebo group.
Preliminary analysis indicates that the UK variant strain was detected in more than 50% of the PCR-confirmed symptomatic cases (32 UK variant, 24 non-variant, six unknown). Efficacy by strain was calculated to be 95.6% against the original COVID-19 strain - putting it in a similar range to Pfizer and Moderna's mRNA vaccines - and 85.6% against the UK variant strain.
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".
Phase 3 trials covering up to 30,000 participants are also under way in Mexico and the US.
Lesser protection against South Africa variant
In the South Africa Phase 2b trial, a total of 29 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.
This study enrolled over 4,400 patients beginning in August 2020, with COVID-19 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 COVID-19 events; of these, 92.6% (25 out of 27 cases) were the South Africa ariant.
This study also included participants who were seropositive, demonstrating prior COVID-19 infection at baseline. These pre-trial infections are thought to have been caused by the original COVID-19 strain; 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," says Novavax.
Novavax has, however, started investigating new vaccines or boosters that could increase efficacy against emerging strains: and says its vaccine can be adapted to new vaccines. The protein-based vaccine is engineered from the genetic sequence of SARS-CoV-2: using Novavax’s recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and adjuvanted with Novavax’ saponin-based Matrix-M to enhance the immune response and stimulate high levels of neutralizing antibodies.
“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.”
Additional analysis on both the Phase 3 UK trial and Phase 2b South Africa trial is ongoing and will be shared via prepublication servers as well as submitted to a peer-reviewed journal for publication.
More visibility on vaccine efficacy against new strains
Given the timings of the trials, Novavax' Phase 3 and 2b trials have been able to gather clinical data on efficacy of its vaccines against the new UK and South Africa strains. The strains have been causing concern over increased transmissability and the unknowns over whether vaccines would protect against these mutated variants.
Novavax's findings are the first to come from large scale clinical trials. Moderna and Pfizer, however, have reported similar findings from their in vitro studies.
On Thursday, Pfizer/BioNTech announced that sera of vaccinated individuals was found to neutralize SARS-CoV-2 strains from both the UK and South Africa. Efficacy against the South Africa strain was slightly lower; but the difference was not great enough to create a cause for concern or prompt development of a new vaccine.
Moderna announced similar findings for its vaccine against new strains. It has, however, started developing a booster shot specifically designed to combat the South Africa strain ‘out of an abundance of caution’, as the protection from its current vaccine against this strain was lower.