ATAGI statement on use of Novavax Covid vaccine

Department of Health

covid-19 vaccine tile

Novavax COVID-19 vaccine, also known as Nuvaxovid (Biocelect Pty Ltd/Novavax Inc) has been provisionally approved by the Therapeutic Goods Administration (TGA) for use in a primary course of vaccination in people aged 18 years and older. Novavax COVID-19 vaccine is a spike protein-based vaccine. Each 0.5mL dose contains 5 micrograms of the of SARS-CoV-2 spike protein and 50 micrograms of Matrix-M as an adjuvant. Novavax COVID-19 vaccine has been demonstrated to be highly effective in preventing symptomatic COVID-19 in adults in a primary schedule, based on phase II-III clinical trials involving over 45,000 participants.

Novavax COVID-19 vaccine is not currently registered by the TGA for use as a COVID-19 booster vaccine.

ATAGI recommendations

  • ATAGI recommends that Novavax COVID-19 vaccine can be used for the primary course of COVID-19 vaccination in people aged 18 or older.
  • The recommended schedule for administration is 2 doses, a minimum of 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 specific precautions for the use of Novavax COVID-19 vaccine.
  • Novavax COVID-19 vaccine can be administered to pregnant and breastfeeding women. ATAGI notes that unlike the Pfizer and Moderna vaccines for which there are substantial data on their safe use in pregnancy and with breastfeeding, there are no immunogenicity or safety data for these groups with the Novavax COVID-19 vaccine. However, there are no theoretical safety concerns relating to use in pregnancy, since the Novavax COVID-19 vaccine, similarly to other COVID-19 vaccines, is not a live vaccine.
  • Novavax COVID-19 vaccine can be administered to people with a prior history of SARS-CoV-2 infection, in line with recommendations for other COVID-19 vaccines.
  • People with severe immunocompromise are recommended to receive 3 primary doses of COVID-19 vaccine, and Novavax COVID-19 vaccine can be used for this purpose. Refer to the ATAGI statement on the use of a 3rd primary dose which is recommended at an interval of 2 months after the 2nd dose.
  • Novavax COVID-19 vaccine can be administered as part of a heterologous (mixed) primary schedule to people who have received one or more doses of another COVID-19 vaccine, including as a third dose for people with severe immunocompromise.
  • Novavax COVID-19 vaccine is not currently recommended for use as a booster vaccine.
  • Novavax COVID-19 vaccine can be co-administered with other vaccines if required.

Background

Vaccine efficacy

Two phase III trials, conducted in the USA/Mexico and in the UK, assessed the efficacy of Novavax COVID-19 vaccine.1,2 Across these trials approximately 27,000 participants received the full 2 doses of vaccine, and approximately 17,000 received a placebo. A phase II trial conducted in South Africa included over 4000 participants and provided data on vaccine efficacy against the Beta variant of SARS-CoV-2.3

Vaccine efficacy (VE) against PCR-confirmed symptomatic mild, moderate or severe COVID-19 in serologically negative adults, with onset at least 7 days after 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 South African phase II trial, VE among 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 American/UK trials and the South African trial has been attributed to the prevalence of the Beta variant in South Africa during the study period, however other contributory factors cannot be excluded.

Special populations

Vaccine efficacy in several pre-specified subgroups was generally consistent with the overall study population. 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 was about 91% (95% CI 70.4 – 95.9%).1,2

Pregnant and breastfeeding women were excluded from the Novavax clinical trials, however animal studies have not indicated any direct or indirect harmful effects relating to pregnancy or embryonic/foetal development.4

There are limited data on the safety and immunogenicity of Novavax COVID-19 vaccine in people with immunocompromise. In the South African phase II trial, among 2684 participants, 6% were HIV positive.3 When including all participants, vaccine efficacy was 49.4% (95%CI 6.1-72.8), however when HIV positive participants were excluded, vaccine efficacy was 60.1% (95%CI 19.9-80.1).3 Neutralising antibody geometric mean titres for HIV-positive participants were comparable in HIV-positive and HIV-negative participants. No safety concerns were highlighted for the HIV positive participants.

Co-administration

A small sub-study (n = 431) of the UK phase III trial assessed the impact of co-administering the first dose of Novavax COVID-19 vaccine or placebo with either a quadrivalent cell-based influenza vaccine (for those aged 18-64) or a trivalent adjuvanted influenza vaccine (in those aged 65 years 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 an efficacy of 89.8% (95%CI 79.7 to 95.5) in the main study for participants aged 18 to 64 years who received Novavax COVID-19 vaccine alone.5 SARS-CoV-2 binding antibody responses were approximately 0.6-fold lower in participants who received the co-administered vaccines compared with those who received Novavax COVID-19 vaccine alone. There were no significant differences in the immune responses to influenza vaccines in the group who received co-administered Novavax COVID-19 vaccine compared with those who received the influenza vaccine with placebo. It is not yet known whether the impact of co-administration on immunogenicity translates to any difference in clinical protection, or duration of protection against COVID-19. Post-introduction assessment of real-world vaccine effectiveness, as for all COVID-19 vaccines, should be conducted to assess clinical protection.

Adverse events were reported more frequently in the co-administration compared with the COVID-19 only vaccine group but were overall mild and of brief duration.

There are currently no data available on the co-administration of Novavax COVID-19 vaccine with other vaccines, but there are no significant theoretical concerns regarding co-administration, which is permissible for all COVID-19 vaccines as per current ATAGI clinical guidance.

Vaccine safety

Safety data from the three phase II-III clinical trials included approximately 34,000 participants.4 Safety monitoring was conducted after each vaccine dose with a median follow up period of around 70 days. In the larger (US/Mexico) phase III trial, local adverse events were reported in around 58% of Novavax COVID-19 vaccine recipients after the first dose, and in around 79% after the second dose.2 The most commonly reported local adverse events were injection site tenderness and pain. Local adverse events were more frequent among younger (age 18-64 years) participants compared with older participants.

Systemic adverse events were reported in 47.7% of Novavax COVID-19 vaccine recipients following dose 1 compared with 69.5% following 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 older adults during the 3 days following vaccination (1% in Novavax COVID-19 vaccine recipients vs 0.6% in placebo recipients).4

A total of three cases of myocarditis were reported in the two phase III trials, of which 2 occurred in the vaccine group and 1 in the placebo group.4

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