AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019
MD Myron J Levin, MD Andrew Ustianowski, MSc Steven Thomas, PhD Alison Templeton, PhD Yuan Yuan, PhD Seth Seegobin, PhD Catherine F Houlihan, MD Ibrahim Menendez-Perez, MBBS Simon Pollett, PhD Rosalinda H Arends, PhD Rohini Beavon, MSc Kanika Dey, MD Pedro Garbes, PhD Elizabeth J Kelly, PhD Gavin C K W Koh, MD Stefan Ivanov, MD Karen A Near, PhD Audrey Sharbaugh, PhD Katie Streicher, PhD Menelas N Pangalos, PhD Mark T Esser
Clinical Infectious Diseases, doi:10.1093/cid/ciac899
Background: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 Methods: Adults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription-polymerase-chain-reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183. Results: 1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442-and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] -25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo. Conclusions: This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.
References
Astrazeneca, Update to Evusheld recommended dosage regimen for pre-exposure prophylaxis of COVID-19
Bader, Mckinsey, Postexposure prophylaxis for common infectious diseases, Am Fam Physician
Bernal, Andrews, Gower, Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on COVID-19 related symptoms, hospital admissions, and mortality in older adults in England: Test negative case-control study, Bmj
Brandal, Macdonald, Veneti, Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to, Euro Surveill
Burugorri-Pierre, Lafuente-Lafuente, Oasi, Investigation of an outbreak of COVID-19 in a French nursing home with most residents vaccinated, JAMA Netw Open
Cao, Yisimayi, Jian, 2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection, Nature
Conte, Golzarri-Arroyo, Tixagevimab and Cilgavimab (Evusheld) boosts antibody levels to SARS-CoV-2 in patients with multiple sclerosis on b-cell depleters, Mult Scler Relat Disord
De Gier, Andeweg, Backer, Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), the Netherlands, Euro Surveill
Dejnirattisai, Huo, Zhou, SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses, Cell
Dong, Zost, Greaney, Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail, Nat Microbiol
Ikematsu, Hayden, Kawaguchi, Baloxavir marboxil for prophylaxis against influenza in household contacts, N Engl J Med
Iketani, Liu, Guo, Antibody evasion properties of SARS-CoV-2 Omicron sublineages, Nature
Lachiewicz, Srinivas, Varicella-zoster virus post-exposure management and prophylaxis: A review, Preventive medicine reports
Lauer, Grantz, Bi, The incubation period of coronavirus disease 2019 (COVID-19) from publicly reported confirmed cases: Estimation and application, Ann Int Med
Levin, Ustianowski, Wit, Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19, N Engl J Med
Loo, Cai, Ren, The SARS-CoV-2 monoclonal antibody combination AZD7442 (tixagevimab/cilgavimab) does not interfere with COVID-19 vaccine-induced immunogenicity ECCMID
Loo, Mctamney, Arends, The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans, Sci Transl Med
Montgomery, Hobbs, Padilla, 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
O'brien, Forleo-Neto, Musser, Subcutaneous REGEN-COV antibody combination to prevent Covid-19, N Engl J Med
O'brien, Forleo-Neto, Sarkar, Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial, Jama
Petros, Turcinovic, Welch, Early introduction and rise of the Omicron SARS-CoV-2 variant in highly vaccinated university populations, Clin Infect Dis,
doi:10.1093/cid/ciac1413Pritchard, Matthews, Stoesser, Impact of vaccination on new SARS-CoV-2 infections in the United Kingdom, Nat Med
Shitrit, Zuckerman, Mor, Gottesman, Chowers, Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population, Israel, July 2021, Euro Surveill
Singanayagam, Hakki, Dunning, Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: A prospective, longitudinal, cohort study, Lancet Infect Dis
Tuekprakhon, Nutalai, Dijokaite-Guraliuc, Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum, Cell
Vanblargan, Errico, Halfmann, An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies, Nat Med
Young-Xu, Epstein, Marconi, Tixagevimab/Cilgavimab for Prevention of COVID-19 during the Omicron Surge: Retrospective Analysis of National VA Electronic Data, medRxiv
Zhou, Wang, Misasi, Structural basis for potent antibody neutralization of SARS-CoV-2 variants including B.1.1.529, Science
Zost, Gilchuk, Case, Potently neutralizing and protective human antibodies against SARS-CoV-2, Nature
Zost, Gilchuk, Chen, Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein, Nat Med
DOI record:
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19)</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>Adults without prior SARS-CoV-2 infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2–infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab consecutively) or placebo. Primary endpoints were safety and first post-dose SARS-CoV-2 reverse-transcription–polymerase-chain-reaction (RT-PCR)–positive symptomatic COVID-19 event before day 183.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>1121 participants were randomized and dosed (mean age 46 years; 49% females; AZD7442, n=749; placebo, n=372). Median (range) follow-up was 49 (5–115) and 48 (20–113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR–positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction 33.3%; 95% confidence interval [CI] –25.9 to 64.7; P=.21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR–negative (n=974 [87%]) or missing an RT-PCR result (n=99 [9%]) at baseline, AZD7442 reduced RT-PCR–positive symptomatic COVID-19 by 73.2% (95% CI 27.1 to 90.1) versus placebo.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusions</jats:title>\n <jats:p>This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined analysis of participants who were SARS-CoV-2 RT-PCR–negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19.</jats:p>\n </jats:sec>",
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