By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
The CDC has endorsed a fourth COVID-19 vaccine, based on a positive recommendation from the CDC Advisory Committee on Immunization Practices.1 Novavax COVID-19 vaccine, adjuvanted (NVX-CoV2373) includes recombinant nanoparticle spike (rS) protein from the Wuhan strain of SARS-CoV-2. A proprietary adjuvant (Matrix-M) was added to boost immunogenicity. This platform differs from the previous approved vaccines, which use mRNA or human adenovirus platforms.
INDICATIONS
The FDA issued an emergency use authorization (EUA) for Novavax. It is authorized to be administered to patients age 18 years and older for active immunization to prevent COVID-19 caused by SARS-CoV-2.2
DOSAGE
The recommended dose for the primary series is two doses (0.5 mL), administered intramuscularly three weeks apart.2 Each 0.5 mL dose contains 5 µg of a rS protein, plus 50 µg of Matrix-M adjuvant.2 The adjuvant is composed of saponin extracts from the soapbark tree, Quillaja saponaria Molina.2
POTENTIAL ADVANTAGES
Novavax provides another vaccine option, especially for patients concerned about mRNA vaccines. The vaccine may be stored up to six months at refrigerated temperatures.
POTENTIAL DISADVANTAGES
Clinical trial data show evidence of higher risk for myocarditis and pericarditis (six per 40,000 compared to one per 40,000 for placebo).3 Reports of cardiomyopathy or cardiac failure were higher with the Novavax vaccine recipients compared to placebo recipients (0.03% compared to less than 0.01%).2 Efficacy was demonstrated early in the SARS-CoV-2 pandemic on initial versions of the virus, such as alpha/B.1.1.7, before the emergence of variants and subvariants.
COMMENTS
The efficacy of Novavax was assessed in a randomized, placebo-controlled study (n = 29,945).2,4 Subjects were randomized in a 2:1 ratio to Novavax or placebo. The primary endpoint was first occurrence of PCR-confirmed symptomatic mild, moderate, or severe COVID-19 at least seven days after the second dose among subjects who were seronegative at baseline. The overall vaccine efficacy, based on an analytical data set (n = 25,657) and a median follow-up of approximately three months, was 90.4% (95% CI, 83.8-94.3). Efficacy against moderate-to-severe disease was 100% (95% CI, 87-100).3 Reactogenicity, local and systemic, appears similar to other vaccines (e.g., local pain tenderness, muscle pain, headache, fatigue) and is more frequent after the second dose.
CLINICAL IMPLICATIONS
Novavax is the fourth COVID-19 vaccine to become available in the United States. The efficacy study was conducted during a time when the B.1.1.7 variant was the dominant strain. That also was the time COVID-19 vaccines became available under early EUAs, which limited the enrollment to older adults.4 During the study, there was imbalance in the number of unblinding requests (those in the placebo arm) to gain access to authorized vaccines. Researchers implemented a blinded crossover three to four months after the first vaccination series to allow all trial participants to receive the Novavax vaccine.4 Myocarditis and pericarditis may be a concern, although these have been associated with mRNA vaccines, too.5,6 Efficacy against newer variants, especially omicron subvariants, is unknown. Considering these issues, the current clinical utility and role in the current SARS-CoV-2 landscape is unknown and difficult to assess. Novavax initiated a Phase III booster study (NCT05372588) in May 2022, targeted to the omicron variant. The study includes an estimated 1,240 previously vaccinated subjects.7 The treatment arms include two doses (day 0 and day 90) of the omicron SARS-CoV-2 rS protein nanoparticle vaccine (NVX-CoV2515), two doses of the Wuhan strain (NVX-CoV2373), and two doses of a bivalent vaccine (NVX-CoV2373 and NVX-CoV2515). Primary endpoints are safety and immunogenicity. Researchers are targeting July 2023 to complete this study.
REFERENCES
1. Centers for Disease Control and Prevention. CDC recommends Novavax’s COVID-19 vaccine for adults. July 19, 2022.
2. U.S. Food & Drug Administration. Emergency use authorization (EUA) of the Novavax COVID-19 vaccine, adjuvanted to prevent coronavirus disease 2019 (COVID-19). July 13, 2022.
3. Rendall J. Novavax: Everything you should know about the newest COVID-19 vaccine. CNET. July 24, 2022.
4. Dunkle LM, Kotloff KL, Gay CL, et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. N Engl J Med 2022;386:531-543.
5. Link-Gelles R, Levy ME, Gaglani M, et al. Effectiveness of 2, 3, and 4 COVID-19 mRNA vaccine doses among immunocompetent adults during periods when SARS-CoV-2 omicron BA.1 and BA.2/BA.2.12.1 sublineages predominated — VISION Network, 10 States, December 2021–June 2022. MMWR Morb Mortal Wkly Rep 2022;71:931-939.
6. Centers for Disease Control and Prevention. Myocarditis and pericarditis after mRNA COVID-19 vaccination. Updated July 14, 2022.
7. ClinicalTrials.gov. Phase 3 booster study for the SARS-CoV-2 rS vaccines.
Novavax is authorized to be administered to patients age 18 years and older for active immunization to prevent COVID-19 caused by SARS-CoV-2.
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