AstraZeneca's Long-Acting Antibody Cocktail Evusheld Receives FDA Emergency Use Authorization for Pre-Exposure Prevention of COVID-19

Author: Shi Bei

On December 8, AstraZeneca announced that the FDA had approved the Emergency Use Authorization (EUA) application for its long-acting antibody cocktail therapy Evusheld (tixagevimab + cilgavimab) for the pre-exposure prophylaxis of SARS-CoV-2. This is the first antibody therapy approved by the FDA for pre-exposure prevention of COVID-19.

Evusheld is a combination of two long-acting antibodies, tixagevimab and cilgavimab. These two antibodies were initially discovered by the Vanderbilt University Medical Center, both derived from B cells of recovered patients, and can bind to different sites of the SARS-CoV-2 spike protein. AstraZeneca obtained the development license in June 2020 and modified the antibody structure using its proprietary YTE half-life extension technology, reducing the ability to bind to Fc receptors and complement C1q. Compared with conventional antibodies, the modified antibodies have a more than threefold extended half-life, providing 12 months of protection with a single injection. Additionally, due to the reduced ability to bind to Fc receptors, the risk of ADE can be minimized.

In August 2021, AstraZeneca announced positive results from the PROVENT study for pre-exposure prophylaxis. The study included 5,197 participants, over 75% of whom had comorbidities and were immunocompromised, potentially requiring additional protection beyond vaccines to avoid SARS-CoV-2 infection. The results showed that AZD7442 reduced the risk of developing COVID-19 symptoms by 77% (95% CI: 46, 90) compared to placebo and was well-tolerated.

Evusheld also has the potential to provide a therapeutic option for patients already infected with the SARS-CoV-2 virus, preventing disease progression. Preclinical in vitro data suggest that AZD7442 possesses broad-spectrum antiviral activity, effective against variants such as Delta and Mu, and is the first antibody combination therapy to demonstrate long-term prevention of COVID-19 in Phase III clinical trials.

On October 11, AstraZeneca announced positive high-level results for the long-acting antibody (LAAB) cocktail therapy AZD7442 in the Phase III TACKLE trial for the treatment of COVID-19. TACKLE is a Phase III randomized, double-blind, placebo-controlled, multi-center trial designed to evaluate the safety and efficacy of a single 600mg intramuscular dose of AZD7442 compared to placebo in outpatient treatment of COVID-19. In this study, 90% of participants were at high risk of progressing to severe COVID-19, including those with comorbidities.

The trial met the primary endpoint. The results showed that, compared with placebo, intramuscular (IM) injection of AZD7442 (600mg) reduced the risk of progressing to severe COVID-19 or death (for any reason) by 50% in outpatients who developed symptoms within 7 days or less. The trial recorded 18 events in the AZD7442 group (18/407) and 37 events in the placebo group (37/415). The LAAB was well tolerated in the trial.

In a pre-specified analysis of subjects who received treatment within 5 days of symptom onset, compared with placebo, AZD7442 reduced the risk of progression to severe COVID-19 or death (for any reason) by 67%. There were 9 events in the AZD7442 group (9/253) and 27 events in the placebo group (27/251).

Compared with placebo, AZD7442 significantly reduced the risk of severe COVID-19 or death in non-hospitalized patients with mild to moderate symptoms of COVID-19. AZD7442 is the first Long-Acting Antibody (LAAB) to demonstrate benefits in both the prevention and treatment of COVID-19 and can be conveniently administered via intramuscular injection.