Novavax NVX-CoV2373 vaccine demonstrates 90% overall efficacy and 100% protection against moderate and severe COVID 19 disease in PREVENT-19 Phase III trial

The study enrolled 29,960 participants across 119 sites in the U.S. and Mexico to evaluate efficacy, safety and immunogenicity, with an emphasis on recruiting a representative population of communities and demographic groups most impacted by the disease.

The company intends to file for regulatory authorizations in the third quarter, upon completion of the final phases of process qualification and assay validation needed to meet chemistry, manufacturing and controls (CMC) requirements. Upon regulatory approvals, Novavax remains on track 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 of 2021.

Results: Consistent, high efficacy among circulating variants : In the placebo-controlled, observer-blinded study randomized 2:1, NVX-CoV2373 demonstrated overall efficacy of 90.4% (95% CI: 82.9, 94.6), achieving its primary endpoint. Seventy-seven cases were observed: 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. Ten moderate cases and four severe cases were observed, all in the placebo group, yielding a vaccine efficacy of 100% (95% CI: 87.0, 100) against moderate or severe disease. Efficacy endpoints were accrued from January 25 through April 30, 2021 — a time when the Alpha (B.1.1.7) variant, first identified in the U.K., became the predominant strain in the U.S. Other strains, including Variants of Interest (VoI) and Variants of Concern (VoC), were also on the rise during the PREVENT-19 endpoint accrual window. Sequence data are available for 54 of the 77 cases.

PREVENT-19 met its key secondary endpoint, demonstrating 100% efficacy (95% CI: 80.8, 100) against variants not considered VoC/VoI. Of the sequenced cases, 35 (65%) were VoC, 9 (17%) were VoI, and 10 (19%) were other variants. Against VoC/VoI, which represented 82% of the cases, vaccine efficacy was 93.2% (95% CI: 83.9, 97.1), achieving a key exploratory endpoint of the study. Thirty-eight of the VoC/VoI cases were in the placebo group and 6 were in the vaccine group. NVX-CoV2373 also showed success among "high-risk" populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure): vaccine efficacy was 91.0% (95% CI: 83.6, 95.0), with 62 COVID-19 cases in the placebo group and 13 COVID-19 cases in the vaccine group.

Results: Reasserting a favorable safety profile : 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.

Study Endpoints : The primary endpoint for PREVENT-19 was the 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. The statistical success criterion included a lower bound of 95% CI >30%. Novavax expects to share further details of the PREVENT-19 trial results as additional data become available. Further analyses of the trial are ongoing and will be shared via preprint servers as well as submitted to peer-review journals for publication. The placebo-controlled portion of PREVENT-19 continues in adolescents from 12 to less than 18 years of age, which recently completed enrollment with 2,248 participants.

Variant Virus Strains : The CDC has defined Variant of Interest (VoI) as a variant with genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, or predicted increase in transmissibility or disease severity. A Variant of Concern (VoC) is defined as a variant for which there is evidence of an increase in transmissibility, more severe disease, significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.