The Therapeutic Goods Administration (TGA) is aware of concerns about decreased effectiveness of monoclonal antibodies (mAbs) against the COVID-19 caused by emerging SAR-COV-2 variants. Other agencies including the FDA, EMA and NIH are also aware and have updated their recommendations accordingly.
The TGA has provisionally approved the following for the treatment and/or prevention of COVID-19:
Monoclonal antibodies that target the SARS-CoV-2 spike protein
- Casirivimab plus imdevimab (RONAPREVE)
- Regdanvimab (REGKIRONA)
- Sotrovimab (XEVUDY)
- Tixagevimab and cilgavimab (EVUSHELD)
Immune modulating monoclonal antibodies
Non monoclonal antibody antiviral agents used in the treatment of COVID 19
Monoclonal antibodies targeting the SARS-CoV-2 spike protein had shown clinical benefits against COVID-19 caused by variants predominant during the earlier stages of the pandemic. These antibodies are designed to neutralise the virus by binding to the spike protein on its surface. However, emerging data show that anti-spike protein monoclonal antibodies demonstrate a significant decrease in their in-vitro neutralising activities against many newer circulating SARS-CoV-2 variants, particularly Omicron and its subvariants. While there are few published clinical trials on the effectiveness of these monoclonal antibodies against clinical disease caused by these newer variants, it is expected that these mAbs will not provide clinical benefit in those people infected with the newer variants.
The activity of the monoclonal antibody tocilizumab is not reduced against variants as this antibody does not target the virus but acts as a modulator of the immune response. Non monoclonal antibody antiviral treatments such as nirmatrelvir/ritonavir (PAXLOVID), molnupiravir (LAGEVRIO) and remdesivir (VEKLURY), which have different mechanisms of action, are likely to retain their activity against the emerging strains.
In Australia, the situation continues to evolve, with the epidemiology of circulating variants changing regularly. The characteristics of the circulating SARS-CoV-2 viruses should be considered when prescribing monoclonal antibodies for prevention or treatment of COVID-19. Healthcare professionals will need to consider alternative treatments as appropriate.
The Communicable Diseases Genomics Network has a role in surveillance and reporting for variants of concern in Australia. Australian COVID 19 epidemiology information is also available. Recent data on the susceptibility of SARS-CoV-2 variants to monoclonal antibodies is available from Stanford University.
At this stage, the regulatory status of the products remain unchanged in Australia. The TGA and its counterparts will continue to monitor the efficacy and safety of all COVID-19 medicines in Australia. Potential updates to the Product Information for individual monoclonal antibodies will be published (if required) as they become available.
References
Uraki, R, Ito M, Kiso, M et al. 2023 Antiviral and bivalent vaccine efficacy against an omicron XBB.1.5 isolate. Lancet Infect Dis. 2023 Feb 8:S1473-3099(23)00070-1.
Cox, M., Peacock, T.P., Harvey, W.T. et al. (2022) SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies. Nat. Rev. Microbiol.
Takashita E, Yamayoshi S, Fukushi S, et al. Efficacy of Antiviral Agents against the Omicron Subvariant BA.2.75. N Engl J Med. 2022 Sep 29;387(13):1236-1238.
Wang Q, Iketani S, Li Z, et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. Cell. 2023 Jan 19;186(2):279-286.e8.
Arora P, Kempf A, Nehlmeier I, Schulz SR, Jack HM, Pohlmann S, et al. Omicron sublineage BQ.1.1 resistance to monoclonal antibodies. Lancet Infect Dis. 2023;23(1):22-3
Chauvin, C, Levillayer, L et al. Tocilizumab-treated convalescent COVID-19 patients retain the cross-neutralization potential against SARS-CoV-2 variants, iScience, 2023; Volume 26, Issue 3
EMA statement
ETF warns that monoclonal antibodies may not be effective against emerging strains of SARS-CoV-2
FDA information
FDA announces Evusheld is not currently authorized for emergency use in the U.S
FDA updates Sotrovimab emergency use authorization
