GAITHERSBURG, Md.—Novavax, Inc. has reported that the company’s COVID-19 vaccine candidate, NVX-CoV2373, has met its primary endpoint with a vaccine efficacy of 89.3%, in its UK Phase 3 clinical trial. The study assessed efficacy during a period of high transmission, with a new UK variant strain of the virus circulating widely. Novavax has also announced successful results of its Phase 2b study of NVX-CoV2373, conducted in South Africa.
“With today’s results from our UK Phase 3 and South Africa Phase 2b clinical trials, we have now reported data on our COVID-19 vaccine from Phase 1, 2, and 3 trials involving over 20,000 participants. In addition, our PREVENT-19 US and Mexico clinical trial has randomized over 16,000 participants toward our enrollment goal of 30,000,” said Stanley C. Erck, president and CEO of Novavax.
“NVX-CoV2373 is the first vaccine to demonstrate not only high clinical efficacy against COVID-19, but also significant clinical efficacy against both the rapidly emerging UK and South Africa variants,” he continued. “NVX-CoV2373 has the potential to play an important role in solving this global public health crisis. We look forward to continuing to work with our partners, collaborators, investigators and regulators around the world to make the vaccine available as quickly as possible.”
The UK study enrolled more than 15,000 participants between 18-84 years of age, with 27% of participants over the age of 65. The primary endpoint of the UK trial is based on the first occurrence of PCR-confirmed symptomatic COVID-19, with onset at least 7 days after the second study vaccination in adult participants who were serologically negative for SARS-CoV-2 at baseline.
The first interim analysis was based on 62 cases — 56 cases of COVID-19 observed in the placebo group, versus 6 cases 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 case from the placebo group becoming severe.
Preliminary analysis indicates that the UK variant strain was detected in over 50% of the PCR-confirmed symptomatic cases (32 UK variant, 24 non-variant, and six unknown). Based on PCR performed on strains from 56 of the 62 cases, vaccine efficacy by strain was calculated to be 95.6% against the original COVID-19 strain, and 85.6% against the UK variant strain (post hoc). The interim analysis also 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.
“These are spectacular results, and we are very pleased to have helped Novavax with the development of this vaccine. The efficacy shown against the emerging variants is also extremely encouraging,” noted Clive Dix, chair of the UK Vaccine Taskforce. “This is an incredible achievement that will ensure we can protect individuals in the UK and the rest of the world from this virus.”
Novavax intends to share further details of the UK trial results, as more data become available. Additional analysis on both trials is ongoing and will be shared via preprint servers, as well as submitted to a peer-reviewed journal for publication. The company has also initiated a rolling submission to the UK’s Medicines and Healthcare products Regulatory Agency in mid-January.
In the Phase 2b trial in South Africa, 60% efficacy (95% CI: 19.9 – 80.1) for the prevention of mild, moderate, and severe COVID-19 disease was observed in the 94% of the study population that was HIV-negative. 29 cases were observed in the placebo group, with 15 seen in the vaccine group. One severe case occurred in the placebo group, and all other cases were mild or moderate. The clinical trial 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 – 72.8).
The South African 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 escape variant.
In the South African trial, approximately a third of patients enrolled — who weren’t 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 believed to have been caused by the original COVID-19 strain, while the subsequent infections during the study were largely from the variant virus. These data suggest that prior infection with COVID-19 may not afford complete protection against subsequent infection by the South Africa escape variant; however, vaccination with NVX-CoV2373 did provide protection.
“The 60% reduced risk against COVID-19 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 COVID-19 vaccine for which we now have objective evidence that it protects against the variant dominating in South Africa,” noted Professor Shabir Maddi, executive director of the Vaccines and Infectious Diseases Analytics Research Unit (VIDA) at Wits, and principal investigator in the South African trial. “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 COVID-19.”
Novavax initiated development of new constructs against the emerging strains in early January, and intends to select candidates for a booster and/or combination bivalent vaccine for the new strains in the near future. 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,” added Dr. Gregory M. Glenn, president of Research and Development at 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.”