AstraZeneca Reports Positive Phase III Results for Long-Acting Antibody Cocktail AZD7442 in Treating COVID-19

Source: PharmaCube Info

Author: Shi Bei

On October 11, AstraZeneca announced that AZD7442, a long-acting antibody (LAAB) cocktail therapy, achieved positive topline results in the Phase III TACKLE trial for the treatment of COVID-19. Compared with placebo, AZD7442 significantly reduced the risk of severe COVID-19 or death in non-hospitalized patients with mild-to-moderate symptoms. AZD7442 is the first LAAB proven to demonstrate benefit in both the prevention and treatment of COVID-19, and can be conveniently administered via intramuscular injection.

AZD7442 is a combination of two long-acting antibodies, tixagevimab and cilgavimab. Originally discovered by the Vanderbilt University Medical Center, both antibodies are derived from the B cells of convalescent patients and bind to distinct epitopes on the SARS-CoV-2 spike protein. AstraZeneca obtained development rights in June 2020 and engineered the antibody structure using its proprietary YTE half-life extension technology, which reduces binding affinity to Fc receptors and complement C1q. Compared to conventional antibodies, the engineered antibodies exhibit a half-life extended by more than threefold, providing 12 months of protection with a single injection. Additionally, the reduced Fc receptor binding capability minimizes the risk of antibody-dependent enhancement (ADE).

TACKLE is a Phase III randomized, double-blind, placebo-controlled, multicenter trial designed to evaluate the safety and efficacy of a single 600 mg intramuscular dose of AZD7442 compared with placebo in the 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 its primary endpoint. Compared with placebo, intramuscular (IM) AZD7442 (600 mg) reduced the risk of progression to severe COVID-19 or death (from any cause) by 50% in outpatients with symptom onset within 7 days. The trial recorded 18 events in the AZD7442 group (18/407) and 37 events in the placebo group (37/415). LAAB was well tolerated in the trial.

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

AstraZeneca stated that it will discuss these data with health authorities. On October 5, 2021, the company announced that it had submitted an Emergency Use Authorization application to the U.S. FDA for AZD7442 for the prevention of COVID-19.

Note: The original text has been abridged.