Novavax, a late-stage biotechnology company, announced phase 1 data from its phase 1/2 randomized, observer-blinded, placebo-controlled trial of its COVID-19 vaccine with and without Matrix-M adjuvant in healthy adults 18-59 years of age. NVX-CoV2373, the company’s recombinant COVID-19 vaccine candidate adjuvanted with Matrix-M, was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera.
Overall, the vaccine was well-tolerated and reactogenicity events were generally mild. Following Dose 1, tenderness and pain were the most frequent local symptoms and systemic events were individually less frequent with headache, fatigue and myalgia being reported most commonly. As expected, following Dose 2, greater reactogenicity was reported, although the majority of symptoms were reported as = Grade 1. The average duration of events was < 2 days.
Unsolicited adverse events were collected through 28 days after Dose 2. There were no severe (Grade 3) unsolicited adverse events and the vast majority of adverse events were mild and deemed not related to vaccination. No serious adverse events (SAEs) were reported and safety follow-up continues.
NVX-CoV2373 induced neutralization titers in 100% of participants; 5 µg adjuvanted dose group peak GMT: 3,906 (95% CI: 2,556; 5,970).
All subjects developed anti-spike IgG antibodies after a single dose of vaccine, many of them also developing wild-type virus neutralizing antibody responses, and after Dose 2, 100% of participants developed wild-type virus neutralizing antibody responses. Both anti-spike IgG and viral neutralization responses compared favorably to responses from patients with clinically significant COVID-19 disease. Importantly, the IgG antibody response was highly correlated with neutralization titers, demonstrating that a significant proportion of antibodies were functional.
The adjuvant was dose-sparing, with the lower 5 µg dose of NVX-CoV2373 performing comparably with the 25 µg dose. Cellular immune responses were measured in a subset of participants, and NVX-CoV2373 induced antigen-specific polyfunctional CD4+ T cell responses with a strong bias toward the Th1 phenotype (IFN-g, IL-2, and TNF-a).
“The phase 1 data demonstrate that NVX-CoV2373 with our Matrix-M adjuvant is a well-tolerated COVID-19 vaccine with a robust immunogenicity profile,” said Gregory M. Glenn, M.D., president, research and development at Novavax. “Using a stringent wild-type virus assay performed by investigators at the University of Maryland School of Medicine, NVX-CoV2373 elicited neutralizing antibody titers greater than those observed in a pool of COVID-19 patients with clinically significant disease.”
The trial was supported by funding from the Coalition for Epidemic Preparedness Innovations (CEPI) and was conducted at two sites in Australia.
Novavax also submitted to a peer-reviewed journal data showing results of NVX-CoV2373 immunization in cynomolgus macaques. The vaccine induced sterile immunity that prevented viral replication in the upper and lower respiratory tracts, thus showing potential to reduce COVID-19 transmission. There was no evidence of enhanced disease following challenge.
NVX-CoV2373 is a 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 contains Novavax’ patented saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. In preclinical trials, NVX-CoV2373 demonstrated indication of antibodies that block binding of spike protein to receptors targeted by the virus, a critical aspect for effective vaccine protection. Novavax was awarded US$ 1.6 billion by the federal government as part of Operation Warp Speed (OWS), a US government programme to deliver millions of doses of a safe, effective vaccine for COVID-19 to the US population. The OWS funding is being used by Novavax to complete late-stage clinical development, including a pivotal phase 3 clinical trial; establish large-scale manufacturing; and deliver 100 million doses of NVX-CoV2373 beginning as early as late 2020.
Novavax’ patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.