AstraZeneca’s COVID-19 therapy hits goal in phase 3, but efficacy falls short of rivals

AstraZeneca has chalked up another win for its anti-SARS-CoV-2 antibody combination, revealing the prospect cut the rate of severe COVID-19 or death in patients recently infected with the coronavirus. But with AstraZeneca arriving late to the market with efficacy results that fall short of its rivals, the commercial prospects of AZD7442 in the treatment of COVID-19 are uncertain.

In recent weeks, AstraZeneca has broken new ground by showing the antibody cocktail cuts the risk of symptomatic COVID-19 and going on to file for emergency use authorization. AstraZeneca’s phase 3 results and work to extend the protection provided by the antibodies out as far as 12 months set AZD7442 apart in the COVID-19 prevention space, but the company will face stiffer competition as it targets the treatment market. 

The good news for AstraZeneca is the treatment trial hit its primary endpoint. Having enrolled more than 800 non-hospitalized patients with mild to moderate symptomatic COVID-19, investigators saw 18 cases of severe disease or death in the AZD7442 arm compared to 37 in the placebo cohort. 

Linking AZD7442 to a 50% reduction in severe COVID-19 or death in high-risk patients, 90% of whom had comorbidities associated with poor coronavirus outcomes, suggests the combination can treat infections. The question of whether the results are good enough to make AZD7442 competitive is less clear-cut.

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Regeneron received EUA for REGN-COV2 after linking the anti-SARS-CoV-2 antibody cocktail to a 70% drop in coronavirus-related hospitalization and all-cause death. Brii Biosciences found its challenger reduced hospitalizations and deaths by 78%.

AstraZeneca fell well short of those numbers ,but, in addition to the standard caveats about cross-trial comparisons, there are specific differences between the studies that may have affected the results and the prospects of AZD7442. Notably, the Regeneron and Brii clinical trials both tested intravenous infusions of the antibodies. Regeneron’s EUA allows subcutaneous doses but “strongly” recommends REGN-COV2 is given intravenously when treating COVID-19.

The AstraZeneca trial tested an intramuscular dose of AZD7442. Intramuscular administration could lower a barrier to uptake of anti-SARS-CoV-2 antibodies, but, as it stands, there is a question mark over efficacy. Clarification of whether the route of administration influences efficacy should come when the National Institutes of Health reports data from its ACTIV-2 study, which tested intramuscular and intravenous versions of AZD7442 in outpatients with COVID-19. The presence of variants in the study populations is another potential factor.   

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