AstraZeneca has started a phase 1 clinical trial of its two-antibody cocktail against COVID-19. The 48-subject trial is set to deliver data later this year and set AstraZeneca up to evaluate the protective and therapeutic effect of the drug in larger phase 2 and 3 studies.
In the trial, AstraZeneca will test multiple intramuscular and intravenous doses of the drug, AZD7442, and a placebo in healthy adults. The trial is primarily designed to gather safety data. Subjects will stay at the clinical research unit for at least 24 hours after receiving AZD7442 and continue to be tracked for about one year after they are discharged.
AstraZeneca will share data from the trial well before the end of the follow-up period. As it stands, AstraZeneca expects to share data before the end of the year. The readout will inform AstraZeneca’s plans for phase 2 and 3 development of AZD7442.
Like other developers of COVID-19 antibodies such as Eli Lilly and Regeneron, AstraZeneca foresees its prospect being used to both treat and prevent the infectious disease. Antibodies could provide an extra layer of protection to vaccinated, high-risk individuals or serve as the sole defense of people who are ineligible for vaccination.
AstraZeneca, which consistently highlighted the prophylactic potential of antibodies in its updates, has extended the half-lives of its candidates in a bid to provide upward of six months of protection. The use of half-life extension technologies sets AstraZeneca apart from other antibody developers such as Regeneron, which advanced unmodified antibodies in the belief it can achieve good duration and durability without making modifications that could come with certain risks.
Researchers investigated the protective power of the AstraZeneca antibodies in rhesus macaques. Monkeys that received an isotype control monoclonal antibody had high levels of subgenomic viral RNA after being exposed to SARS-CoV-2. No subgenomic viral RNA was found in the monkeys that received 50 mg/kg of one of two types of anti-SARS-CoV-2 antibody as a monotherapy.
The same paper also assessed the therapeutic potential of the antibodies. At the most efficient dose, around 20 mg/kg, four out of five mice had no detectable levels of infectious virus in the lung.
Work on the drug dates back to the early days of the coronavirus crisis, when scientists at Vanderbilt University Medical Center isolated 389 spike-protein-reactive monoclonal antibodies from the B cells of two convalescing people who were infected in Wuhan, China. The work led to the identification of antibodies that target non-overlapping sites on the protein the virus uses to enter human cells.
AstraZeneca soon signed up to evaluate the antibodies. In June, AstraZeneca licensed six antibodies from Vanderbilt and outlined plans to start a clinical trial to evaluate a combination of two of them within two months.
The timeline has put AstraZeneca a little behind the COVID-19 antibody front-runners. Eli Lilly took its asset, LY-CoV555, into the clinic in late May and initiated a phase 2 trial in mild to moderate patients the following month. A phase 3 assessment of LY-CoV555’s ability to prevent COVID-19 got underway earlier this month.
Regeneron began phase 1/2 trials of its cocktail in ambulatory and hospitalized COVID-19 patients in early June. A phase 3 trial to assess the protective power of REGN-COV2 began later that month. Regeneron added an early-phase assessment of repeated subcutaneous doses of its antibodies in healthy volunteers to its slate of studies last week.