AZD7442 (Evusheld): A Comprehensive Monograph on a Long-Acting Monoclonal Antibody Combination for COVID-19

Executive Summary

AZD7442, commercially known as Evusheld, represents a landmark achievement in the global response to the COVID-19 pandemic. Developed by AstraZeneca, this biotech therapeutic is a combination of two long-acting monoclonal antibodies, tixagevimab and cilgavimab, designed to provide passive immunity against SARS-CoV-2. Its development was predicated on a critical unmet medical need: the protection of immunocompromised and other high-risk individuals who are unable to mount an adequate immune response to vaccination. Through sophisticated molecular engineering, including modifications to extend its half-life and enhance its safety profile, AZD7442 was positioned as the first long-acting antibody for pre-exposure prophylaxis (PrEP) against COVID-19.

The clinical development program for AZD7442 was robust, comprising three pivotal Phase III trials that evaluated its efficacy across the spectrum of disease prevention and treatment. The PROVENT trial unequivocally demonstrated its prophylactic efficacy, showing a 77% reduction in the risk of developing symptomatic COVID-19, with protection lasting at least six months. Conversely, the STORM CHASER trial failed to meet its primary endpoint for post-exposure prophylaxis, providing crucial evidence on the therapeutic window for passive immunization. The TACKLE trial successfully established its utility as an early outpatient treatment for mild-to-moderate COVID-19, significantly reducing the risk of progression to severe disease, particularly when administered within three days of symptom onset.