Safety, Efficacy and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Treatment of Mild-to-Moderate COVID-19: 15-Month Final Analysis of the TACKLE Trial

Springer Science and Business Media LLC - Tập 13 Số 3 - Trang 521-533 - 2024
F D Richard Hobbs1,2, H. E. Montgomery3, Francisco Padilla4, Jesus Abraham Simón Campos5, Douglas Arbetter6, Seth Seegobin7, Alexandre Kiazand8, Katie Streicher9, Nuria Martinez-Alier7, Taylor S. Cohen9, Mark T. Esser10
1NIHR Applied Research Collaboration (ARC) Oxford Thames Valley, Oxford, UK.
2Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK
3Department of Medicine, University College London, London, UK
4Centro de Investigación en Cardiología y Metabolismo, Guadalajara, Jalisco, Mexico.
5Köhler and Milstein Research/Méchnikov Project, Universidad Autonoma de Yucatan, Mérida, Yucatán, Mexico.
6Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Boston, MA, USA.
7Vaccines and Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
8Patient Safety, Chief Medical Office, R&D and Vaccines and Immune Therapies, AstraZeneca, Gaithersburg, MD, USA.
9Vaccines and Immune Therapies, BioPharmaceuticals R&D, Astrazeneca, 1 Medimmune Way, Gaithersburg, MD, 20878, USA.
10Vaccines and Immune Therapies, BioPharmaceuticals R&D, Astrazeneca, 1 Medimmune Way, Gaithersburg, MD, 20878, USA. [email protected].

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Zost SJ, Gilchuk P, Case JB, et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 2020;584(7821):443–9.

Loo YM, McTamney PM, Arends RH, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med. 2022;14(635):eabl8124.

Robbie GJ, Criste R, Dall’acqua WF, et al. A novel investigational Fc-modified humanized monoclonal antibody, motavizumab-YTE, has an extended half-life in healthy adults. Antimicrob Agents Chemother. 2013;57(12):6147–53.

Yu XQ, Robbie GJ, Wu Y, et al. Safety, tolerability, and pharmacokinetics of MEDI4893, an investigational, extended-half-life, anti-Staphylococcus aureus alpha-toxin human monoclonal antibody, in healthy adults. Antimicrob Agents Chemother. 2017;61(1):e01020–e1116.

Oganesyan V, Gao C, Shirinian L, Wu H, Dall’Acqua WF. Structural characterization of a human Fc fragment engineered for lack of effector functions. Acta Crystallogr D Biol Crystallogr. 2008;64:700–4.

European Medicines Agency. Evusheld: EPAR - Product information. 2022. https://www.ema.europa.eu/en/documents/product-information/evusheld-epar-product-information_en.pdf. Accessed 8 January 2024.

AstraZeneca. Evusheld long-acting antibody combination approved for prevention and treatment of COVID-19 in Japan. 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/evusheld-approved-for-covid-19-in-japan.html. Accessed 8 January 2024.

AstraZeneca Canada Inc. EVUSHELD. Tixagevimab and cilgavimab injection. Product monograph including patient medication information. 2022. https://covid-vaccine.canada.ca/info/pdf/evusheld-pm-en.pdf. Accessed 8 January 2024.

Australian Government Department of Health and Aged Care. Therapeutic Goods Administration. Evusheld. 2022. https://www.tga.gov.au/resources/auspmd/evusheld-0. Accessed 8 January 2024.

Imai M, Ito M, Kiso M, et al. Efficacy of antiviral agents against Omicron subvariants BQ.1.1 and XBB. N Eng J Med. 2023;388(1):89–91.

Arora P, Kempf A, Nehlmeier I, et al. Omicron sublineage BQ 1 1 resistance to monoclonal antibodies. Lancet Infect Dis. 2022;23(1):S1473-3099.

Wang Q, Li Z, Ho J, et al. Resistance of SARS-CoV-2 omicron subvariant BA 4.6 to antibody neutralisation. Lancet Infect Dis. 2022;22(12):1666–8.

United States Food and Drug Administration. FDA announces Evusheld is not currently authorized for emergency use in the U.S. 2023. https://www.fda.gov/drugs/drug-safety-and-availability/fda-announces-evusheld-not-currently-authorized-emergency-use-us. Accessed 8 January 2024.

Montgomery H, Hobbs FDR, Padilla F, et al. Efficacy and safety of intramuscular administration of tixagevimab-cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2022;10(10):985–96.

Hobbs FDR, Montgomery H, Padilla F, et al. Outpatient treatment with AZD7442 (tixagevimab/cilgavimab) prevented COVID-19 hospitalizations over 6 months and reduced symptom progression in the TACKLE randomized trial. Infect Dis Ther. 2023;12(9):2269–87.

Forte-Soto P, Albayaty M, Brooks D, et al. Safety, tolerability and pharmacokinetics of half-life extended severe acute respiratorysyndrome coronavirus 2 neutralizing monoclonal antibodies AZD7442 (tixagevimab-cilgavimab) in healthy adults. J Infect Dis. 2023;227(10):1153–63.

Levin MJ, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (tixagevimab-cilgavimab) for prevention of Covid-19. N Engl J Med. 2022;386(23):2188–200.

ACTIV-3–Therapeutics for Inpatients with COVID-19 (TICO) Study Group. Tixagevimab-cilgavimab for treatment of patients hospitalised with COVID-19: a randomised, double-blind, phase 3 trial. Lancet Respir Med. 2022;10(10):P972–84.

Clegg LE, Stepanov O, Schmidt S, et al. Consistency of AZD7442 (cilgavimab/tixagevimab) pharmacokinetics across prophylaxis and treatment and adult and pediatric participants: application of population pharmacokinetics to enable rapid decision-making during the COVID-19 pandemic. Open Forum Infect Dis. 2023. https://doi.org/10.1093/ofid/ofad500.464.

Okada H, Ishikawa K, Itoh Y, et al. Safety, tolerability, and pharmacokinetics of half-life extended SARS-CoV-2-neutralizing monoclonal antibodies AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults. J Infect Chemother. 2023;29:1061–7.

Akinosoglou K, Rigopoulos EA, Kaiafa G, et al. Tixagevimab/cilgavimab in SARS-CoV-2 prophylaxis and therapy: a comprehensive review of clinical experience. Viruses. 2022;15(1):118.

Elias LB, Jaber A, Manzano M, Leekoff M, Sylvester A, Tremblay MA. Real-world efficacy of COVID-19 pre-exposure prophylaxis with tixagevimab/cilgavimab in people with multiple sclerosis. Vaccines (Basel). 2023;11(12):1855.

Al Jurdi A, Morena L, Cote M, Bethea E, Azzi J, Riella LV. Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave. Am J Transplant. 2022;22(12):3130–6.

Angelico R, Romano F, Coppola L, et al. Effects of anti-COVID-19 vaccination and pre-exposure prophylaxis with tixagevimab-cilgavimab in kidney and liver transplant recipients. Medicina (Kaunas). 2023;59(12):2101.

Evans RA, Dube S, Lu Y, et al. Impact of COVID-19 on immunocompromised populations during the Omicron era: insights from the observational population-based INFORM study. Lancet Reg Health-Eur. 2023;35: 100747.

Ketkar A, Willey V, Pollack M, et al. Assessing the risk and costs of COVID-19 in immunocompromised populations in a large United States commercial insurance health plan: the EPOCH-US Study. Curr Med Res Opin. 2023;39(8):1–16.