Tixagevimab/cilgavimab or placebo for COVID-19 in ACTIV-2: Safety, pharmacokinetics and neutralizing and anti-drug antibodies
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.
Authors
- Kara W Chew (ORCID: https://orcid.org/0000-0003-4865-4348)
- Rachel Bender Ignacio (ORCID: https://orcid.org/0000-0001-6167-1447)
- Courtney Vail Fletcher (ORCID: https://orcid.org/0000-0002-3703-7849)
- Carlee Moser (ORCID: https://orcid.org/0000-0001-5601-9112)
- Arzhang Cyrus Javan
- Jonathan Z. Li (ORCID: https://orcid.org/0000-0001-9914-9662)
- Rinki Deo
- Davey M. Smith (ORCID: https://orcid.org/0000-0003-3603-1733)
- David A. Wohl (ORCID: https://orcid.org/0000-0002-7764-0212)
- M.R.J. Gibbs (ORCID: https://orcid.org/0000-0003-1978-3378)
- Manish C. Choudhary (ORCID: https://orcid.org/0000-0002-3192-7840)
- Eric S. Daar (ORCID: https://orcid.org/0000-0003-1880-7331)
- Mark J Giganti (ORCID: https://orcid.org/0000-0003-2255-9756)
- Judith S. Currier (ORCID: https://orcid.org/0000-0003-4279-4737)
- Justin Ritz (ORCID: https://orcid.org/0000-0001-6307-4849)
- Hervé Tchouakam Kouekam
- Michael D. Hughes (ORCID: https://orcid.org/0000-0001-8562-2316)
- Mark T. Esser
- Joseph J. Eron
Institutions
- AstraZeneca (United Kingdom) (GB)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Harvard University (US)
- University of California, Los Angeles (US)
- University of Washington (US)
- UCLA Medical Center (US)
- University of California System (US)
- University of California San Diego (US)
- Fred Hutch Cancer Center (US)
- National Institute of Allergy and Infectious Diseases (US)
- AstraZeneca (United States) (US)
- Harbor–UCLA Medical Center (US)
- University of Nebraska Medical Center (US)
Publication Details
- Journal
- iScience
- Published
- 2025-02-04
- DOI
- https://doi.org/10.1016/j.isci.2025.111938
- Citations
- 1
- Primary Topic
- SARS-CoV-2 and COVID-19 Research
- Type
- article
- Field-Weighted Citation Impact
- 1.40
Funders
- AstraZeneca
- ACT Government
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases