FLC | Agency-funded Novavax COVID-19 vaccine shows early promise in trial

Agency-funded Novavax COVID-19 vaccine shows early promise in trial

August 5, 2020

The $1.6 billion invested in Novavax in early July by the US Department of Health and Human Services and the Department of Defense as part of Operation Warp Speed is starting to pay off. The Gaithersburg, Maryland company announced on August 4 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. The data have been submitted for peer-review to a scientific journal and to an online preprint server at medRxiv.org.

NVX-CoV2373 was well-tolerated and had a reassuring safety profile. Overall, the vaccine was well-tolerated and treatment-related adverse 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 equal to or lower than Grade 1. The average duration of events was less than two 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. 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.

Matrix-M™ adjuvant induced robust polyfunctional CD4+ T cell responses. 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 findings also suggest that NVX-CoV2373 is stable and amenable to handling in a liquid formulation that can be stored at 2°C to 8°C, allowing for successful cold chain management with existing infrastructure.

“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, MD, President of 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.”

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. These data have also been submitted to an online preprint server at medRxiv.org.

The trial was supported by funding from the Coalition for Epidemic Preparedness Innovations (CEPI) and was conducted at two sites in Australia.