Novavax COVID-19 vaccine potently immunogenic with room to lower dose

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Although prime-boost administration of the likely Phase II dose of Novavax’s COVID-19 vaccine led to severe adverse events in a small proportion of Phase I volunteers, the human immunogenicity and baboon protection data suggest there’s room to lower the protein-based vaccine’s dose.

The data make Novavax at least the third COVID-19 vaccine developer to show its candidate can induce sterilizing immunity in non-human primates.

Gregory Glenn, Novavax Inc. (NASDAQ:NVAX) president of R&D, said similar neutralizing titers and T cell responses between groups receiving low and high doses of NVX-CoV2373 plus the company’s Matrix-M adjuvant implied that the vaccine was at the top of its dose-response curve. If that is the case, then the company could decrease the dose, which also could stretch supply. Glenn presented the data on a webcast Tuesday.

President and CEO Stanley Erck reiterated Novavax’s goal to make the vaccine globally available but tempered expectations that the company would deliver 100 million doses to the U.S. by year-end. Glenn gave that target July 21 at the Second International Society for Vaccines COVID-19 Vaccines Virtual Congress (see “Novavax On Track to Deliver”).

Novavax aims to have “tens of millions of doses available toward the end of this year and a hundred million doses available early in the first quarter of next year in the U.S., and a similar amount in Europe,” said Erck.

He said the company has submitted the data to FDA to enable a U.S. and Australian Phase II trial in about 1,500 people. The Phase II trial will include patients older than the 131 volunteers ages 18-59 in the placebo-controlled Phase I study, he said.

Novavax has a $1.6 billion contract from the Biomedical Advanced Research and Development Authority (BARDA) and the Department of Defense (DoD) under Operation Warp Speed to develop the full-length recombinant spike protein nanoparticle vaccine. The deal is the initiative’s third largest (see “$8.3B Across Seven Vaccines”).

The company has also received $388 million from the Coalition for Epidemic Preparedness Innovations (CEPI).

Neutralizing antibodies, T cells

In the Phase I portion of the Phase I/II trial, prime-boost administration of 5 or 25 μg NVX-CoV2373 plus 50 μg Matrix-M led to neutralizing geometric mean titers of 3,906 and 3,305, respectively. The neutralizing antibody titers are about four times higher than the convalescent sera average of 983 -- a titer comparable to that gathered from COVID-19 patients in an outpatient setting.

Non-adjuvanted 25 μg NVX-CoV2373 led to neutralizing titers of 41, about 100 times lower than the adjuvanted doses, as well as little to no T cell responses.

Glenn also showed that both adjuvanted doses of NVX-CoV2373 induced CD4+ T cell responses with a Th1 bias.

Th2 responses have been associated with vaccine-associated enhanced respiratory disease.

The adjuvanted lower dose, which is the likely Phase II dose, led to severe systemic adverse events (AEs) -- myalgia, fatigue and arthralgia but not fever -- in about 5% of volunteers. About 20% of the participants had moderate AEs and about 40% had mild symptoms.

A small percentage of participants in the placebo group also had severe systemic AEs.

Prior to showing the clinical data, Glenn highlighted data demonstrating sterilizing immunity in all baboons vaccinated twice with the adjuvanted NVX-CoV2373 doses used in the Phase I study, as well as all but one of the four baboons given a lower dose: 2.5 NVX-CoV2373 plus 25 μg Matrix-M.

The one monkey in which SARS-CoV-2 RNA was detected had lower viral levels in lung fluid two days after infection than all of the control animals as well as no detectable virus in nasal samples at the time point. Four days after challenge, lung and nasal samples were clear of the virus.

Moderna Inc. (NASDAQ:MRNA), which is partnered with NIH, and Johnson & Johnson (NYSE:JNJ) have already demonstrated that their vaccines can induce sterilizing immunity in non-human primates. J&J’s data also suggested that high neutralizing antibody titers could be enough to rapidly shut down SARS-CoV-2 replication (see “Non-human Primate Data Shed Light on Correlates of Protection”; “Moderna’s COVID-19 Vaccine Protects Monkeys”).

Novavax shares were up $13.83 to $171 in after-hours trading.

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