New analyses were announced from the phase 3 PROVENT and TACKLE trials evaluating the efficacy and safety of AZD7442 for the prevention of COVID-19.
AZD7442 is a combination of 2 long-acting monoclonal antibodies, tixagevimab and cilgavimab, derived from B-cells donated by convalescent patients who were infected with the SARS-CoV-2 virus. The investigational antibodies are designed to bind to distinct sites on the SARS-CoV-2 spike protein with an extended half-life and reduced Fc receptor and complement C1q binding.
PROVENT (ClinicalTrials.gov Identifier: NCT04625725) is a multicenter, randomized, double-blind, placebo-controlled trial that included 5197 participants aged 18 years and older who would benefit from 2 long-acting antibodies, defined as having increased risk for inadequate response to active immunization or having increased risk of SARS-CoV-2 infection. At the time of screening, participants were unvaccinated and had a negative point-of-care SARS-CoV-2 serology test. Participants were randomly assigned 2:1 to receive a single intramuscular (IM) dose of either 300mg of AZD7442 or saline placebo, administered in 2 separate IM injections.
At a median follow-up of 6 months, results showed that AZD7442 achieved an 83% risk reduction of developing symptomatic COVID-19 compared with placebo. There were no cases of severe COVID-19 or COVID-19-related deaths in the AZD7442 treatment arm at either the primary or 6-month analyses compared with 2 additional cases of severe COVID-19 in the placebo arm for a total of 5 cases, including 2 deaths. These results support the previously reported primary analysis from August 2021, which showed a 77% risk reduction of developing symptomatic COVID-19.
TACKLE (ClinicalTrials.gov Identifier: NCT04723394) is a multicenter, randomized, double-blind, placebo-controlled trial that included 903 participants aged 18 years and older who were non-hospitalized with mild to moderate COVID-19 and symptomatic for 7 days or less. Participants had a documented laboratory-confirmed SARS-CoV-2 infection and were randomly assigned 1:1 to receive 2 separate, sequential IM injections of either AZD7442 or saline placebo.
According to an exploratory analysis of the TACKLE trial, findings showed that one 600mg IM dose of AZD7442 achieved an 88% risk reduction of developing severe COVID-19 or death (from any cause) among patients who were symptomatic for 3 days or less compared with placebo.
Full data from both trials will be submitted for publication in a peer-reviewed medical journal and presented at a forthcoming medical meeting. AstraZeneca has submitted a request to the Food and Drug Administration (FDA) for Emergency Use Authorization for AZD7442 for the prevention of COVID-19.
Hugh Montgomery, Professor of Intensive Care Medicine at University College London, UK and AZD7442 principal investigator, said: “These compelling results give me confidence that this long-acting antibody combination can provide my vulnerable patients with the long-lasting protection they urgently need to finally return to their everyday lives. Importantly, six months of protection was maintained despite the surge of the Delta variant among these high-risk participants who may not respond adequately to vaccination.”
New analyses of two AZD7442 COVID-19 phase III trials in high-risk populations confirm robust efficacy and long-term prevention. News release. AstraZeneca. Accessed November 18, 2021. https://www.businesswire.com/news/home/20211118005506/en/New-Analyses-of-Two-AZD7442-COVID-19-Phase-III-Trials-in-High-Risk-Populations-Confirm-Robust-Efficacy-and-Long-Term-Prevention.