PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults

Abstract: LB5. PROVENT: Phase 3 Study of Efficacy and Safety of AZD7442 (Tixagevimab/ Cilgavimab) for Pre-exposure Prophylaxis of COVID-19 in Adults Myron J. Levin, MD1; Andrew Ustianowski, MBBS2; Stéphane De Wit, MD3; Odile Launay, MD, PhD4; Miles Avila, MPH, GStat5; Seth Seegobin, PhD5; Alison Templeton, PhD5; Yuan Yuan, PhD6; Philip Ambery, FRCP5; Rosalinda H. Arends, PhD5; Rohini Beavon, PhD5; Karen A. Near, MD5; Kelly W. Padilla, PharmD5; Konstantina Psachoulia, PhD5; Audrey Sharbaugh, PhD5; Katie Streicher, PhD5; Menelas N. Pangalos, PhD5; Mark T. Esser, PhD5; Robert A. Gasser, Jr., MD5; 1University of Colorado Anschutz Medical Campus, Aurora, CO; 2North Manchester General Hospital, Manchester, England, United Kingdom; 3CHU St-Pierre, Brussels, Brussels Hoofdstedelijk Gewest, Belgium; 4Université de Paris, Inserm F-CRIN I-REIVAC, Paris, Ile-de-France, France; 5AstraZeneca, Gaithersburg, Maryland; 6AstraZeneca, Gaithersburg, MD, USA, Gaithersburg, Maryland Session: 55. Late Breaker Abstracts: COVID-19 Treatment & Prophylaxis Thursday, September 30, 2021: 6:15 PM Background. Vaccines effectively prevent COVID-19, but some individuals have medical comorbidities or receive therapies that impair their immune response to vaccination, or are ineligible for vaccination. For such individuals who remain at risk of COVID-19, monoclonal antibodies may provide additional rapid protection. AZD7442 comprises 2 fully human extended half-life SARS-CoV-2–neutralizing antibodies that bind distinct epitopes of the viral spike protein receptor binding domain. AZD7442 is in development for the prevention and treatment of COVID-19. Here, we report primary Phase 3 study results of AZD7442 for pre-exposure prophylaxis of symptomatic COVID-19. Methods. PROVENT (NCT04625725) is a Phase 3, 2:1 randomized, double-blind, placebo-controlled study of a single 300-mg AZD7442 dose (2 intramuscular injections; 150 mg each of tixagevimab and cilgavimab) for symptomatic COVID-19 prevention. Participants were unvaccinated adults (≥ 18 years old) without prior SARS-CoV-2 infection, who may benefit from immunoprophylaxis with antibodies due to an increased risk of either inadequate response to vaccination or SARS-CoV-2 exposure. The primary study endpoints were first case of SARS-CoV-2 RT-PCR-positive symptomatic illness post dose and prior to Day 183 (efficacy), and safety of AZD7442. Results. In total, 5197 participants (mean age 53.5 years, 46% female) were randomized and dosed (safety analysis set): AZD7442 n=3460; placebo n=1737. In the primary efficacy analysis (full pre-exposure analysis set, n=5172), AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval S810 • OFID 2021:8 (Suppl 1) • Late Breaking Abstracts 46.0, 90.0) vs placebo (P< 0.001) (Table). Adverse events occurred in 35% and 34% of participants administered AZD7442 and placebo, respectively, and injection site reactions occurred in 2.4% and 2.1% of participants, respectively (safety analysis set). There was 1 case of severe/critical COVID-19 and 2 COVID-19–related deaths in the placebo arm. Conclusion. The primary study endpoints were met: a one-time dose of AZD7442 demonstrated statistically significant protection against symptomatic COVID-19 and was well tolerated. AZD7442 is the first long-acting monoclonal antibody combination that represents a potential new option to augment COVID-19 prevention. PROVENT funding statement image Disclosures. Myron J. Levin, MD, GSK..