Eli Lilly has begun clinical development of an anti-SARS-CoV-2 antibody designed to work against all currently known circulating variants of concern. The action comes weeks after the FDA revoked the single use emergency authorization of Lilly’s first COVID-19 antibody due to the rise of variants.
Researchers have shown COVID-19 antibodies including Lilly’s bamlanivimab are less effective against variants of concern such as B.1.351 than the original SARS-CoV-2 virus when given as monotherapies. The research, coupled to the emergence of variants of concern as the dominant causes of COVID-19 in parts of the world, has led to reassessments of the use of antibodies as single agents.
AbCellera, which worked with Lilly on bamlanivimab, responded to variants by searching the blood of a patient who recovered from COVID-19 for an antibody that is effective against them. The result is LY-CoV1404, an antibody that binds to a conserved part of the receptor-binding domain.
The targeted region is distinct from the mutations seen in variants and the parts targeted by existing neutralizing antibodies. To assess whether that translates into the neutralization of variants, AbCellera, Lilly and their collaborators pitted LY-CoV1404 against the original SARS-CoV-2 and the B.1.1.7, B.1.351, P.1, B.1.526, B.1.427 and B.1.429 versions that have arisen around the world.
LY-CoV1404 retained full neutralization potency against all the tested variants. Against the original SARS-CoV-2, LY-CoV1404 had potency values ranging from 9 ng/mL to 22.1 ng/mL. Bamlanivimab and S309, a Vir Biotechnology antibody that fared well against variants in another study, were found to be less potent. The potency opens the door to subcutaneous administration.
Lilly is now set to test whether the preclinical promise translates into clinical efficacy. The Big Pharma has added LY-CoV1404 to BLAZE-4, a clinical trial testing multiple antibodies as single agents and combinations in patients with mild-to-moderate COVID-19.
The addition of LY-CoV1404 to BLAZE-4 keeps the candidate on the course that AbCellera sketched out in March. At that time, AbCellera CEO Carl Hansen, Ph.D., said the goal was to get into the clinic in the second quarter and secure emergency use authorization by the midpoint of the year.