January 24, 2022
The Novavax COVID-19 vaccine, also known as Nuvaxovid (Biocelect Pty Ltd/Novavax Inc) has been tentatively approved by the Therapeutic Goods Administration (TGA) for use as part of primary vaccination in people aged 18 and over. The Novavax COVID-19 vaccine is an advanced protein-based vaccine. Each 0.5ml dose contains 5 micrograms of SARS-CoV-2 spike protein and 50 micrograms of Matrix-M as an adjuvant. The Novavax COVID-19 vaccine has been shown to be highly effective in preventing symptomatic COVID-19 in adults in a primary regimen, based on phase II-III clinical trials involving over 45,000 participants.
The Novavax COVID-19 vaccine is not currently registered by the TGA for use as a COVID-19 booster vaccine.
- ATAGI recommends that the Novavax COVID-19 vaccine can be used for the primary treatment of vaccination against COVID-19 in people aged 18 years or older.
- The recommended administration schedule is 2 doses, spaced at least 3 weeks apart.
- Contraindications to vaccination are anaphylaxis to a previous dose of Novavax COVID-19 vaccine or to a component of the vaccine (e.g. polysorbate 80).
- There are no special precautions for using the Novavax COVID-19 vaccine.
- The Novavax COVID-19 vaccine can be given to pregnant and breastfeeding women. ATAGI notes that unlike the Pfizer and Moderna vaccines for which there is substantial data on their safe use in pregnancy and lactation, there are no immunogenicity or safety data for these groups with the vaccine. Novavax COVID-19. However, there are no theoretical safety issues with use in pregnancy, as the Novavax COVID-19 vaccine, like other COVID-19 vaccines, is not a live vaccine.
- The Novavax COVID-19 vaccine can be given to people with a history of SARS-CoV-2 infection, as recommended for other COVID-19 vaccines.
- Severely immunocompromised people are recommended to receive 3 primary doses of COVID-19 vaccine, and the Novavax COVID-19 vaccine can be used for this purpose. Refer to the ATAGI statement on using a 3rd primary dose which is recommended at an interval of 2 months after the 2n/a dose.
- The Novavax COVID-19 vaccine can be given as part of a heterologous (mixed) primary regimen to people who have received one or more doses of another COVID-19 vaccine, including as a third dose for immunocompromised people severe.
- The Novavax COVID-19 vaccine is not currently recommended as a booster vaccine.
- The Novavax COVID-19 vaccine can be co-administered with other vaccines if needed.
Two phase III trials, conducted in the United States/Mexico and the United Kingdom, evaluated the efficacy of the Novavax COVID-19 vaccine.1.2 In these trials, about 27,000 participants received the full 2 doses of vaccine and about 17,000 received a placebo. A phase II trial conducted in South Africa included more than 4,000 participants and provided data on the efficacy of the vaccine against the beta variant of SARS-CoV-2.3
Vaccine efficacy (VE) against PCR-confirmed mild, moderate, or severe symptomatic COVID-19 in serologically negative adults, with onset at least 7 days after the 2nd dose was 90.4% (95% CI 82.88 – 94.62) in the US/Mexico trial, and 89.7% (95% CI 80.2 – 94.6%) in the UK trial.1.2 The estimated VE against moderate or severe COVID-19 was 100% (95% CI 80.9 – 100) in the USA/Mexico trial and 86.9% (95% CI 73.7 – 93 .5%) in the UK trial.1.2 In the phase II trial in South Africa, the VE in HIV-negative adults was 60.1% (95% CI 19.9 – 80.1%) overall, and specifically against the beta variant was estimated at 51% (95% CI -0.6 to 76.2).3 The significant difference in VE estimates between the US/UK trials and the South African trial was attributed to the prevalence of the beta variant in South Africa during the study period, but others contributing factors cannot be excluded.
Vaccine efficacy in several pre-specified subgroups was generally consistent with the overall study population. The VE in adults aged 65 years or older was 88.9% (95% CI 20.2 – 99.7) and in adults with a comorbid medical condition it was approximately 91% (CI at 95% 70.4 – 95.9%).1.2
Pregnant and nursing women were excluded from clinical trials of Novavax, however animal studies did not indicate direct or indirect harmful effects related to pregnancy or embryonic/foetal development.4
There are limited data on the safety and immunogenicity of the Novavax COVID-19 vaccine in immunocompromised people. In the South African phase II trial, among 2684 participants, 6% were HIV positive.3 Including all participants, vaccine effectiveness was 49.4% (95% CI 6.1-72.8), but when HIV-positive participants were excluded, vaccine effectiveness was 60.1% (95% CI 19.9-80.1).3 Geometric mean neutralizing antibody titers for seropositive participants were comparable in seropositive and seronegative participants. No safety issues were identified for HIV-positive participants.
A small substudy (n=431) of the UK phase III trial assessed the impact of co-administering the first dose of the Novavax COVID-19 vaccine or a placebo with a quadrivalent influenza vaccine based on of cells (for people aged 18 to 64). ) or a trivalent influenza vaccine with adjuvant (in people 65 years of age or older).5
Vaccine efficacy against laboratory-confirmed symptomatic COVID-19 was 87.5% (95% CI -0.2 to 98.4) in the co-administration group aged 18 to 64 years, compared with 89.8% efficacy (95% CI 79.7 to 95.5) in the main study for participants aged 18 to 64 who received the Novavax COVID-19 vaccine alone.5 Binding antibody responses to SARS-CoV-2 were approximately 0.6 times lower in participants who received the co-administered vaccines compared to those who received the Novavax COVID-19 vaccine alone. There were no significant differences in immune responses to influenza vaccines in the group that received the co-administered Novavax COVID-19 vaccine compared to those who received the influenza vaccine with a placebo. It is not yet known whether the impact of co-administration on immunogenicity translates into a difference in clinical protection or duration of protection against COVID-19. A post-introduction evaluation of real-world vaccine efficacy, as with all COVID-19 vaccines, should be performed to assess clinical protection.
Adverse events were reported more frequently in the co-administered group compared to the COVID-19 vaccine-only group, but were generally mild and of short duration.
There are currently no data available on co-administration of the Novavax COVID-19 vaccine with other vaccines, but there are no significant theoretical concerns regarding co-administration, which is permitted for all vaccines COVID-19 according to current ATAGI clinical guidelines.
Safety data from the three Phase II-III clinical trials included approximately 34,000 participants.4 Safety monitoring was performed after each vaccine dose with a median follow-up period of approximately 70 days. In the largest phase III trial (US/Mexico), local adverse events were reported in approximately 58% of Novavax COVID-19 vaccine recipients after the first dose, and in approximately 79% after the second dose.2 The most commonly reported local adverse events were tenderness and pain at the injection site. Local adverse events were more common in younger participants (aged 18 to 64) than in older participants.
Systemic adverse events were reported in 47.7% of Novavax COVID-19 vaccine recipients after dose 1 compared to 69.5% after dose 2.4 The most common solicited systemic adverse events were headache, myalgia, fatigue, and malaise, with a median duration of events of 2 days or less.
Serious adverse events were rare. There was a numerical imbalance in the reported incidence of hypertension in the elderly within 3 days of vaccination (1% in Novavax COVID-19 vaccine recipients versus 0.6% in placebo recipients) .4
A total of three cases of myocarditis were reported in the two phase III trials, including 2 in the vaccine group and 1 in the placebo group.4 Of the two cases in the vaccinated group, one was a healthy young participant with onset 3 days after dose 2, and the other was a participant over the age of 65. There is currently no additional information released on these cases. Based on this very small number of cases with limited information and the total number of trial participants, which is insufficient for the detection of very rare adverse events such as myocarditis, it is not possible to determine whether there is a causal relationship or to estimate the risk of myocarditis associated with this vaccine. The occurrence of these cases is not necessarily attributable to this vaccine. It is recommended that all COVID-19 vaccinated be aware of the potential signs and symptoms of myocarditis or pericarditis, and know when to seek medical attention. For more information see ATAGI’s advice on myocarditis and pericarditis.
ATAGI will continue to assess further data on the safety and efficacy of the Novavax COVID-19 vaccine as it emerges, including in special populations and as a booster vaccine, and provide recommendations updates if necessary.
- Heath, PT et al. Safety and efficacy of the NVX-CoV2373 Covid-19 vaccine. New England Journal of Medicine 385, 1172-1183, doi:10.1056/NEJMoa2107659 (2021).
- Dunkle, LM et al. Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico. New England Journal of Medicine, doi: 10.1056/NEJMoa2116185 (2021).
- Shinde, V. et al. Efficacy of the NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N English J med 384, 1899-1909, doi: 10.1056/NEJMoa2103055 (2021).
- Agency, EM Nuvaxovid: EPAR – Public Assessment Report, (2021).
- Toback, S. et al. Safety, immunogenicity and efficacy of a COVID-19 (NVX-CoV2373) vaccine co-administered with seasonal influenza vaccines: an exploratory sub-study of a randomized, observer-blinded phase 3 trial and placebo-controlled. The Lancet Respiratory Medicine, doi: 10.1016/S2213-2600(21)00409-4.