Phase 3 Trial Shows AZ Antibody Combination Reduces Risk of Severe COVID-19, Death in High Risk Groups

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AstraZeneca’s (AZ) investigational long-acting antibody (LAAB) combination AZD7442 achieved a statistically significant reduction in severe COVID-19 or death compared to placebo in non-hospitalized patients with mild-to-moderate symptomatic COVID-19, according to a company statement on Monday, October 11, 2021.

The promising high-level results are from the AZ phase 3 TACKLE COVID-19 treatment trial in which the LAAB reduced by 50% vs placebo the risk of developing severe COVID-19 or death. Further, approximately 90% of trial participants were from populations at high risk for progression to severe infection, according to AZ.

The announcement follows the company’s October 5th notice that it had filed a request with the US Food and Drug Administration for an emergency use authorization for AZD7442 for prophylaxis of symptomatic COVID-19. According to the AZ statement, AZD7442, administered via intramuscular injection, is the first LAAB with phase 3 data demonstrating benefit in both prophylaxis and treatment of COVID-19.

“With continued cases of serious COVID-19 infections across the globe, there is a significant need for new therapies like AZD7442 that can be used to protect vulnerable populations from getting COVID-19 and can also help prevent progression to severe disease,” said TACKLE principal investigator Hugh Montgomery, professor of intensive care medicine at Medicine at University College London, in the company statement. Added Menge Pangalos, AZ executive vice president, biopharmaceuticals R&D, “An early intervention with our antibody can give a significant reduction in progression to severe disease, with continued protection for more than six months.”

The phase 3 TACKLE clinical trial included 903 participants, randomized 1:1 to receive AZD7442 (n=452) or placebo (n=451) administered in 2 separate sequential IM injections. Participants were outpatients aged ≥18 years with confirmed mild-to-moderate CVOID-19 who had been symptomatic for ≤7 days.

The primary efficacy endpoint was the composite of either severe COVID-19 or death from any cause through day 29.

In the final participant group, 13% were aged ≥65 years, 90% had comorbidities at baseline that increased their risk of progression to severe COVID-19 (see sidebar). Approximately 62% were White/Caucasian, 4% Black/African American, 6% Asian, and 24% American Indian or Alaskan Native.

The trial met its primary endpoint, with a dose of 600mg of AZD7442 reducing the risk of developing severe COVID-19 or death (from any cause) by 50% in patients symptomatic for 7 days or fewer vs placebo. Among the 407 participants receiving AZD7442, there were 18 events. There were 37 events among the 415 participants receiving placebo.

Results of a prespecified analysis of participants who were given treatment within 5 days of symptom onset demonstrated that AZD7442 reduced the risk of developing severe COVID-19 or death (from any cause) by 67% compared vs placebo. In this analysis, there were 9 events among 253 participants receiving AZD7442 and 27 events among the 251 who received placebo.

Subjects will continue to be followed for 15 months, the statement says.

“These important results for AZD7442…add to the growing body of evidence for use of this therapy in both prevention and treatment of COVID-19,” added Pangalos in the AZ statement.

Full results from TACKLE will be submitted for publication in a peer-reviewed medical journal and presented at a forthcoming medical meeting.