Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies
Summary: Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infu...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001981 |
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| author | Rachel A. Bender Ignacio Kara W. Chew Carlee Moser Judith S. Currier Joseph J. Eron Arzhang Cyrus Javan Mark J. Giganti Justin Ritz Michael Gibbs Hervé Tchouakam Kouekam Mark T. Esser Eric S. Daar Manish Choudhary Rinki Deo Courtney V. Fletcher Jonathan Z. Li Michael D. Hughes Davey Smith David Alain Wohl |
| author_facet | Rachel A. Bender Ignacio Kara W. Chew Carlee Moser Judith S. Currier Joseph J. Eron Arzhang Cyrus Javan Mark J. Giganti Justin Ritz Michael Gibbs Hervé Tchouakam Kouekam Mark T. Esser Eric S. Daar Manish Choudhary Rinki Deo Courtney V. Fletcher Jonathan Z. Li Michael D. Hughes Davey Smith David Alain Wohl |
| author_sort | Rachel A. Bender Ignacio |
| collection | DOAJ |
| description | Summary: Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported. The analyzed IM group included 214 participants, and the IV group, 106 participants. Adverse events were not different between treatment and placebo. The half-life of both components was >90 days for IM or 75 days for IV. New anti-drug antibodies were about 3 times more likely in active vs. placebo recipients. SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants. |
| format | Article |
| id | doaj-art-8d4caab7ae3d4432b2deecca1e6a78c6 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-8d4caab7ae3d4432b2deecca1e6a78c62025-08-20T03:16:34ZengElsevieriScience2589-00422025-03-0128311193810.1016/j.isci.2025.111938Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodiesRachel A. Bender Ignacio0Kara W. Chew1Carlee Moser2Judith S. Currier3Joseph J. Eron4Arzhang Cyrus Javan5Mark J. Giganti6Justin Ritz7Michael Gibbs8Hervé Tchouakam Kouekam9Mark T. Esser10Eric S. Daar11Manish Choudhary12Rinki Deo13Courtney V. Fletcher14Jonathan Z. Li15Michael D. Hughes16Davey Smith17David Alain Wohl18Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA, USA; Vaccine and Infectious Disease Division, Fred Hutch Cancer Center, Seattle, WA, USA; Corresponding authorDivision of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USADivision of Infectious Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USADivision of Infectious Diseases, Department of Medicine, University of Carolina School of Medicine, Chapel Hill, NC, USANational Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USAVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USAVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UKVaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UKDivision of HIV Medicine, Lundquist Institute, Harbor-UCLA Medical Center, Los Angeles, CA, USADivision of Infectious Diseases, Department of Medicine, Harvard Medical School, Boston, MA, USADivision of Infectious Diseases, Department of Medicine, Harvard Medical School, Boston, MA, USAUNMC Center for Drug Discovery, University of Nebraska Medical Center, Omaha, NE, USADivision of Infectious Diseases, Department of Medicine, Harvard Medical School, Boston, MA, USADepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USADivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, San Diego, CA, USADivision of Infectious Diseases, Department of Medicine, University of Carolina School of Medicine, Chapel Hill, NC, USASummary: Monoclonal antibodies have potential as rapidly developable agents for treatment and prevention of emerging viruses. The ACTIV-2 trial randomized persons with mild-moderate COVID-19 to the monoclonal antibody combination tixagevimab/cilgavimab via intramuscular injection (600 mg IM) or infusion (300 mg IV) versus placebo. We present final safety and laboratory outcomes; primary outcomes were previously reported. The analyzed IM group included 214 participants, and the IV group, 106 participants. Adverse events were not different between treatment and placebo. The half-life of both components was >90 days for IM or 75 days for IV. New anti-drug antibodies were about 3 times more likely in active vs. placebo recipients. SARS-CoV-2 neutralizing antibodies increased 157-fold at 7 days and 127-fold at 1 month (IM-treated) but were less robust in IV participants. These data can inform future development of monoclonal antibodies against SARS-CoV-2 and other viruses, even if this intervention is of low utility for contemporary SARS-CoV-2 variants.http://www.sciencedirect.com/science/article/pii/S2589004225001981Health sciencesMedicineMedical specialtyImmunology |
| spellingShingle | Rachel A. Bender Ignacio Kara W. Chew Carlee Moser Judith S. Currier Joseph J. Eron Arzhang Cyrus Javan Mark J. Giganti Justin Ritz Michael Gibbs Hervé Tchouakam Kouekam Mark T. Esser Eric S. Daar Manish Choudhary Rinki Deo Courtney V. Fletcher Jonathan Z. Li Michael D. Hughes Davey Smith David Alain Wohl Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies iScience Health sciences Medicine Medical specialty Immunology |
| title | Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies |
| title_full | Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies |
| title_fullStr | Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies |
| title_full_unstemmed | Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies |
| title_short | Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies |
| title_sort | tixagevimab cilgavimab or placebo for covid 19 in activ 2 safety pharmacokinetics and neutralizing and anti drug antibodies |
| topic | Health sciences Medicine Medical specialty Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001981 |
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