AstraZeneca has talked up the prospects of its anti-SARS-CoV-2 antibody working in severe COVID-19 patients despite rival assets from Eli Lilly and Regeneron failing in that population. Mene Pangalos, Ph.D., an AstraZeneca executive vice president, made the comments while sharing news the antibody is set to start a prophylaxis study next week.
The COVID-19 antibodies in clinical development have potentially important differences. Regeneron took unmodified antibodies into the clinic in the belief it could achieve sufficient durability without exposing itself to perceived risks of engineering. Lilly’s lead candidate is also a full antibody.
AstraZeneca, in contrast, modified the Fc region of its antibodies. The Fc region does not act on the target antigen but can still have biological effects, for example by activating the immune system. By modifying the Fc region, researchers can change the half-life of an antibody or tweak its effect on the immune system.
The modifications made by AstraZeneca have largely been seen in the context of their effect on half-life so far. However, with the unmodified Fc region fingered as a possible cause of the setbacks Lilly and Regeneron have suffered in severe COVID-19 patients, other implications of AstraZeneca’s action are now coming to the fore.
“The fact that we’ve inactivated the Fc domain in terms of Fc receptor binding, and the fact that we’re going with much lower doses, I think means that we may have a better chance of seeing some activity or some efficacy in that more severe patient population,” Pangalos told investors on a third-quarter results conference call.
The National Institutes of Health (NIH) is set to test AstraZeneca’s candidate in hospitalized patients as part of the same ACTIV-3 phase 3 that evaluated Lilly’s LY-CoV555 in the population. The trial will test an intravenous infusion of an as-yet-undecided dose of AstraZeneca’s antibody.
Pangalos discussed AstraZeneca’s involvement in ACTIV-3 as part of a breakdown of its clinical trials. AstraZeneca plans to start testing a 300-mg intramuscular dose in immune-compromised patients, who are vulnerable and may not respond well to vaccines, next week. Pangalos said the U.K. alone has 500,000 immune-compromised patients
Another planned study will give a 600-mg intramuscular dose to everybody in care homes that has a COVID-19 case. By immunizing everyone with the antibody, AstraZeneca could potentially prevent the fatal outbreaks that hit care homes during the first wave of COVID-19 cases. Two outpatient trials, one sponsored by AstraZeneca, another by NIH, are also in the works.
The prophylaxis, post-exposure and outpatient treatment studies are evaluating intramuscular, and in some cases intravenous, doses of 300 mg and 600 mg. That sets AstraZeneca apart from Regeneron and, to a lesser extent, Lilly. Regeneron is taking forward the 2400-mg dose of its antibody cocktail in outpatient settings. Lilly, which only has one antibody in its lead candidate, chose the 700-mg dose. Both drugs are given intravenously, although Regeneron is testing a subcutaneous formulation.
Pangalos thinks the differences between the assets could be meaningful “We think, overall, the half-life, the route of administration and the dose give us a real competitive advantage relative to the other antibodies,” the AstraZeneca executive said.