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Published in: Infectious Diseases and Therapy 6/2024

Open Access 04-05-2024 | COVID-19 | Original Research

Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials

Authors: Myron J. Levin, Andrew Ustianowski, Stephane De Wit, Rohini Beavon, Jesse Thissen, Seth Seegobin, Kanika Dey, Karen A. Near, Katie Streicher, Alexandre Kiazand, Mark T. Esser

Published in: Infectious Diseases and Therapy | Issue 6/2024

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Abstract

Introduction

The phase 3 PROVENT and STORM CHASER studies evaluated AZD7442 (tixagevimab/cilgavimab) for pre-exposure and post-exposure prophylaxis of symptomatic coronavirus disease 2019 (COVID-19). We report the final 15-month results of both studies.

Methods

In PROVENT, participants were randomized 2:1 to receive 300 mg AZD7442 (n = 3460) or placebo (n = 1737). In STORM CHASER, participants were enrolled within 8 days of exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individual and randomized 2:1 to receive 300 mg AZD7442 (n = 749) or placebo (n = 372).

Results

In PROVENT, the relative risk reduction (RRR) in symptomatic COVID-19 for AZD7442 versus placebo was 76.7% at primary analysis [95% confidence interval (CI) 46.1, 90.0; p < 0.001], 83.0% at day 183 (95% CI 67.3, 91.2; nominal p < 0.001), and 46.3% at day 366 (95% CI 23.1, 62.4; nominal p < 0.001). Severe/critical COVID-19 was reduced by 91.4% with AZD7442 versus placebo by day 366 (95% CI 61.3, 98.1; nominal p < 0.0001). Adverse events (AEs) occurred in 58.2% and 58.0% of participants administered AZD7442 or placebo, respectively; serious AEs (SAEs) occurred in 6.2% and 5.6%, respectively.
In STORM CHASER, the RRR in symptomatic COVID-19 for AZD7442 versus placebo was 33.3% at primary analysis (95% CI − 25.9, 64.7; p = 0.212), 43.3% at day 183 (95% CI 1.4, 67.4; nominal p = 0.044) and 3.4% at day 366 (95% CI − 35.6, 31.2; nominal p = 0.842). Severe/critical COVID-19 did not occur in participants receiving AZD7442 versus 0.5% of participants receiving placebo by day 366. AEs occurred in 46.5% and 51.9% of participants administered AZD7442 or placebo, respectively; SAEs occurred in 2.7% and 4.3%, respectively. In both studies, serum concentration–time profiles over 457 days were similar for tixagevimab and cilgavimab and consistent with the extended half-life reported for AZD7442 (approximately 90 days).

Conclusion

This analysis provides proof of concept supporting long-term safety of intramuscularly administered AZD7442 for prevention of symptomatic/severe COVID-19.
A graphical abstract is available with this article.

Clinicaltrials.gov Identifiers

PROVENT (NCT04625725) and STORM CHASER (NCT04625972).

Graphical abstract

Appendix
Available only for authorised users
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Metadata
Title
Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials
Authors
Myron J. Levin
Andrew Ustianowski
Stephane De Wit
Rohini Beavon
Jesse Thissen
Seth Seegobin
Kanika Dey
Karen A. Near
Katie Streicher
Alexandre Kiazand
Mark T. Esser
Publication date
04-05-2024
Publisher
Springer Healthcare
Published in
Infectious Diseases and Therapy / Issue 6/2024
Print ISSN: 2193-8229
Electronic ISSN: 2193-6382
DOI
https://doi.org/10.1007/s40121-024-00970-x

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