AstraZeneca is seeking Emergency Use Authorization (EUA) for AZD7442, a combination of 2 long-acting monoclonal antibodies for prophylaxis of symptomatic COVID-19.
The investigational antibodies, tixagevimab and cilgavimab, are designed to bind to distinct sites on the SARS-CoV-2 spike protein. According to the Company, the antibody therapy has been optimized with half-life extension that could afford up to 12 months of protection from COVID-19 with a single administration.
The submission is supported by data from the phase 3 PROVENT (ClinicalTrials.gov Identifier: NCT04625725) and STORM CHASER (ClinicalTrials.gov Identifier: NCT04625972) trials, which compared the efficacy and safety of AZD7442 to placebo for pre-exposure and post-exposure prophylaxis, respectively, of COVID-19 in participants 18 years of age and older. Participants were randomly assigned 2:1 to receive a single intramuscular dose of either 300mg of AZD7442 or saline placebo, administered as 2 separate intramuscular injections.
The primary endpoint for both trials was incidence of the first case of SARS-CoV-2 reverse transcriptase-polymerase chain reaction positive symptomatic illness occurring post dose prior to day 183.
Findings from the PROVENT trial (N=5172) showed that AZD7442 reduced the risk of developing symptomatic COVID-19 by 77% (95% CI, 46-90) compared with placebo. There were no cases of severe COVID-19 or COVID-19-related deaths in the AZD7442 treatment arm compared with 3 cases of severe COVID-19 in the placebo arm, including 2 deaths.
Findings from the STORM CHASER trial (N=1121) showed that in the overall trial population (primary analysis), AZD7442 reduced the risk of developing symptomatic COVID-19 by 33% (95% CI, -26, 65) compared with placebo, which was not statistically significant. In a pre-planned subgroup analysis, AZD7442 reduced the risk of developing symptomatic COVID-19 by 73% (95% CI, 27-90) vs placebo, in participants who were PCR negative at the time of dosing. A post-hoc analysis showed that in PCR-negative participants, AZD7442 was associated with a 92% (95% CI, 32-99) reduction in risk more than 7 days following dosing, and a 51% (95% CI, -71, 86) reduction in risk up to 7 days following dosing.
“With this first global regulatory filing, we are one step closer to providing an additional option to help protect against COVID-19 alongside vaccines,” said Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca. “We look forward to sharing AZD7442 data for the treatment of COVID-19 later this year.”
- AZD7442 request for Emergency Use Authorization for COVID-19 prophylaxis filed in US. News release. AstraZeneca. Accessed October 5, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/azd7442-request-for-emergency-use-authorization-for-covid-19-prophylaxis-filed-in-us.html.
- Update on AZD7442 STORM CHASER trial in post-exposure prevention of symptomatic COVID-19. News release. AstraZeneca. June 15, 2021. Accessed October 5, 2021. https://www.astrazeneca.com/media-centre/press-releases/2021/update-on-azd7442-storm-chaser-trial.html.