AstraZeneca has announced positive results from its PROVENT phase 3 trial that show that AZD7442, a combination of two long-acting antibodies, reduced the risk of developing symptomatic COVID-19 by 77% compared to placebo.
The trial studied more than 5,000 participants who did not have SARS-CoV-2 infection at baseline. During the trial, 25 people developed symptomatic disease including three cases of severe COVID-19 (including two deaths) in the placebo arm but there were no cases of severe disease or death in the treated cohort.
More than two-fifths of participants were 60 years and over and three-quarters had co-morbidities, which included conditions that can cause a reduced immune response to vaccination.
AZD7442 is the first antibody combination modified to provide long-lasting protection that has demonstrated efficacy in preventing COVID-19 in a clinical trial. It is a combination of tixagevimab (AZD8895) and cilgavimab (AZD1061), which were derived from B-cells donated by convalescent patients after SARS-CoV-2 virus.
In June, an earlier phase 3 trial – the snappily titled STORM CHASER – which tested the combination in people who had been exposed to the virus, did not meet its primary endpoint.
“The PROVENT data shows that one dose of AZD7442, delivered in a convenient intramuscular form, can quickly and effectively prevent symptomatic COVID-19,” said principal investigator and professor of paediatrics and medicine at the University of Colorado school of medicine, Myron Levin.
The ease of administration for AZ antibody combination has been highlighted. “This antibody combination treatment can be given via an intramuscular injection which makes it simpler to use in a community setting, as opposed to Ronapreve which is given via intravenous infusion,” commented Penny Ward, visiting professor in pharmaceutical medicine at Kings College, London.
Regeneron’s Ronapreve/REGEN-COV, an antibody cocktail of casirivimab and imdevimab, is approved under emergency or temporary authorisations in more than 20 countries and was approved for use in the UK last week.
Discovered by Vanderbilt University Medical Center, AstraZeneca’s human monoclonal antibody combination has been optimised to extend its half-life, more than tripling the “durability of its action” compared to conventional antibodies, said the company.
“In addition it appears to be very long lasting with a single administration potentially offering protection for up to 12 months,” said Penny Ward. “This could be very important as an option for patients at high risk from COVID-19 infection who have responded poorly to vaccination or who must take immune-suppressing treatment for other disease… it could potentially be game changing for these individuals, who are currently being advised to continue to shield despite being fully vaccinated.”
“We need additional approaches for individuals who are not adequately protected by COVID-19 vaccines,” said Mene Pangalos, AZ executive vice president of BioPharmaceuticals R&D. “We look forward to sharing further data from the AZD7442 phase 3 clinical trial programme later this year.”
AstraZeneca will prepare regulatory submission of the prophylaxis data from both PROVENT and STORM CHASER for health authorities for potential emergency use authorisation or conditional approval.
AZ licensed AZD7442 in 2020 from Vanderbilt University and, under the terms of the licensing agreement, the company will pay single-digit royalties on future net sales.