Novavax said today it will file for FDA approvals in the third quarter for its COVID-19 vaccine NVX-CoV2373, after it showed 90.4% overall efficacy, and 93% efficacy against the five most prevalent SARS-CoV-2 variants “of concern” and eight more variants “of interest,” in a Phase III trial.

“Today, Novavax is one step closer to addressing the critical and persistent global public health need for additional COVID-19 vaccines,” Novavax president and CEO Stanley C. Erck said in a statement.

Overall efficacy data from Novavax’s PREVENT-19 pivotal Phase III trial (NCT04611802) met the study’s primary endpoint—first occurrence of PCR-confirmed symptomatic (mild, moderate or severe) COVID-19 with onset at least 7 days after the second dose in serologically negative (to SARS-CoV-2) adult participants at baseline.

In PREVENT-19, 77 COVID-19 cases were seen—63 in the placebo group and 14 in the vaccine group. All cases observed in the vaccine group were mild as defined by the trial protocol.vaccines

NVX-CoV2373 is a stable, prefusion protein made using Novavax’ proprietary nanoparticle technology, and incorporating its proprietary saponin-based Matrix-M™ adjuvant.

The vaccine demonstrated 100% protection against moderate and severe disease, based on 10 moderate cases and four severe cases being observed, all in the placebo group. NVX-CoV2373 also showed 91% efficacy in “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure). Thirteen COVID-19 cases were reported in patients treated with the vaccine, and the other 62, with placebo.

In addition, PREVENT-19 met a key exploratory endpoint of the study by showing 93.2% efficacy against both “variants of concern” (VoC) and “variants of interest (VoI).

Investors sent shares of Novavax rising 7% in premarket trading as of 9:27 a.m., to $225.08 from Friday’s close of $209.68. Shares plateaued after that, finishing the day down 0.94% to $207.71 before inching up 0.5% to $208.70 in after-hours trading as of 8 p.m. ET.

“A Viable alternative”

“These results come in higher than Street expectations of 80–85% and clearly position NVAX as a viable alternative to mRNA vaccines,” Kelechi Chikere, PhD, Equity Analyst with Jefferies, wrote this morning in a research note. “We are particularly encouraged by these results given the high percentage of cases due to variants and believe the data position NVAX to compete against the mRNA vaccines.

Chikere said Novavax’s vaccine should see success worldwide since:

  • Only 10–15% of the world has received one vaccine dose to date.
  • Experts have increasingly concluded that booster shots will be needed, potentially positioning Novavax’s vaccine as a “universal booster” given its high efficacy and mild side effect profile.
  • The vaccine offers ease of transportation/storage. Novavax has told GEN that NVX-CoV2373 requires shipping and storage at 2º to 8º C, negating the need for ultra-low temperature storage required by some mRNA-based vaccines.

“With the U.S. data in hand, investor focus shifts to execution on EUA [emergency use authorization] filings in Q3 and ramping vaccine production,” Chikere added. “Key to NVAX will be their ability to execute on filing their data to the various regulatory agencies for EUA approval, ability to manufacture doses of their vaccine, and procure additional contracts.

Novavax said its FDA filing will come after it completes final phases of process qualification and assay validation needed to meet chemistry, manufacturing and controls (CMC) requirements.

The company did not specify in its statement whether the filing it will pursue will be the EUA it has long discussed with FDA regulators, or a full BLA approval. Late last month, the FDA said it may not review new EUA requests from COVID-19 developers that had not commenced such discussions—though Novavax has had such talks.

Upon regulatory approvals, Novavax said, it is on course to reach manufacturing capacity of 100 million doses per month by the end of the third quarter and 150 million doses per month by the end of the fourth quarter.

Variant, safety data

Variants of concern (VoC) include B.1.1.7 (Alpha/first detected in the United Kingdom); B.1.351 (Beta/South Africa); B.1.427/B.1.429 (Epsilon/California); P.1 (Gamma/Japan and Brazil).

Variants of interest (VoI) include B.1.525 (Eta/U.K. and Nigeria); B.1.526 (Iota/New York); B.1.526.1 (New York); B.1.617 (India); B.1.617.1 (Kappa/India); B.1.617.2 (Delta/India); B.1.617.3 (India); and P.2 (Zeta/Brazil).

The variant data was based on sequencing data that was available for 54 of the 77 COVID-19 cases seen in the study. Of the sequenced cases, 35 (65%) were VoC, 9 (17%) were VoI, and 10 (19%) were other variants.

Novavax’s latest variant data was more positive than the mixed results reported in January from two other trials, when the company showed 89.3% efficacy against B.1.1.7 (Alpha/U.K.) in a Phase III trial in the U.K., but only 60% efficacy in a Phase IIb trial in South Africa against B.1.351 (Beta/Soutrh Africa).

Novavax said preliminary safety data from PREVENT-19 showed the vaccine to be generally well-tolerated. Serious and severe adverse events were low in number and balanced between vaccine and placebo groups.

No single adverse event term was reported by more than 1% of participants. In assessing reactogenicity 7 days after Dose 1 and Dose 2, injection site pain and tenderness, generally mild to moderate in severity, were the most common local symptoms, lasting less than 3 days. Fatigue, headache and muscle pain were the most common systemic symptoms, lasting less than 2 days.

Novavax said further analyses of PREVENT-19 were ongoing and will be shared via preprints as well as in studies to be submitted for publication to peer-review journals.

PREVENT-19 (PRE-fusion protein subunit Vaccine Efficacy Novavax Trial | COVID-19) enrolled 29,960 participants ages 18 and older across 119 sites in the U.S. and Mexico to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373, with an emphasis on recruiting a representative population of communities and demographic groups most impacted by COVID-19, Novavax said.

Second data set in three days

The data reported by Novavax today represented the second dataset announced by the company in three days.

Novavax on June 11 said NVX-CoV2373 and a new vaccine directed against variants showed strong immunogenicity and protection against two SARS-CoV-2 variants—B.1.1.7 (Alpha/U.K.) and B.1.351 (Beta/South Africa)—in three studies by researchers from the company and University of Maryland School of Medicine. One study was conducted in mice, another in baboon, and a third in human samples.

The researchers posted data from the studies in a preprint posted June 9 in bioRxiv. The findings showed:

  • Novavax’s new vaccine based on the recombinant spike protein antigen (rS-B.1.351) from Beta was highly immunogenic in mice and produced neutralizing antibodies.
  • Primates boosted with rS-B.1.351 induced strong neutralizing immune response to original SARS-CoV-2, Alpha and Beta.
  • Humans immunized with original NVX-CoV2373 vaccine demonstrated robust antibody responses to original SARS-CoV-2 strain, as well as to Alpha and Beta.

“These data suggest that not only could one booster dose of this variant-directed vaccine potentially provide a robust, protective immune boost after vaccination against the original SARS-CoV-2 virus, but also the potential to provide broad protection against various virus strains if used as a primary vaccine regimen,” said Gregory M. Glenn, MD, Novavax’s president of Research and Development.

NVX-CoV2373 is among 22 “Front Runner” leading COVID-19 candidates of more than 300 candidates ranked by GEN in its updated COVID-19 DRUG & VACCINE CANDIDATE TRACKER.

“Novavax continues to work with a sense of urgency to complete our regulatory submissions and deliver this vaccine, built on a well understood and proven platform, to a world that is still in great need of vaccines,” Erck added.