Regeneron, Lilly move toward subcutaneous mAb cocktails to treat COVID
Plus: IV infusion of Lilly’s combo reduces outpatient risk
Companies developing mAbs against COVID-19 are moving to subcutaneous injection to ameliorate deployment problems that have plagued their uptake.
FDA has authorized REGEN-COV (casirivimab/imdevimab) from Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) and bamlanivimab from Eli Lilly and Co. (NYSE:LLY) and AbCellera Biologics Inc. (NASDAQ:ABCL) in the outpatient setting. But both are administered IV, creating logistical barriers that have limited their use.
Regeneron reported on Tuesday early data from its prophylactic Phase III study showing subcutaneous injection of REGEN-COV reduced symptomatic and asymptomatic COVID-19, and shorted infection times in those who contracted SARS-CoV-2.
Separately, Lilly revealed plans to test subcutaneous bamlanivimab plus etesevimab, which it developed with Shanghai Junshi Biosciences Co. Ltd. (HKEX:1877; Shanghai:688180). The pharma reported Phase III data Tuesday showing IV infusion of the combination, which is under FDA review, reduced hospitalizations and mortality.
Regeneron’s subcutaneous data
In an exploratory analysis of the first 409 subjects in a Phase III trial to prevent COVID-19 in individuals with COVID-19-positive household contacts, subcutaneous REGEN-COV reduced SARS-CoV-2 infection rates by 48% versus placebo, and completely prevented symptomatic cases.
Infections in the cocktail group lasted ≤1 week vs. three to four weeks in the placebo cohort, and average peak viral loads were over 100 times lower in individuals given REGEN-COV.
Confirmatory results from the trial, run with NIH’s National Institute of Allergy and Infectious Diseases, are expected early next quarter. If the readout holds up in the full trial population, subcutaneous REGEN-COV could become an easier-to-administer bridge to immunity for individuals who haven’t yet been vaccinated.
Regeneron, which is also testing subcutaneous REGEN-COV in a Phase II outpatient study, will discuss the prevention data and potential expansion of the cocktail’s EUA with regulatory agencies.
Lilly will evaluate subcutaneous injection of its mAb cocktail in a third arm of its Phase III BLAZE-1 study to treat mild-to-moderate COVID-19 in high-risk outpatients.
FDA is currently evaluating an EUA request for Lilly’s IV cocktail based on data from the Phase II portion of BLAZE-1.
Phase III data from the trial reported Tuesday showed IV infusion of the combination reduced hospitalization or death due to COVID-19 through day 29 by 70% vs. placebo (p=0.0004). No patient treated with the mAbs died by day 29, whereas 8/10 deaths in the placebo group were COVID-related.
The mAbs also lowered viral loads and led to a greater proportion of patients who resolved all symptoms.
The antibodies in Regeneron’s and Lilly’s cocktails are effective against the majority of SARS-CoV-2 variants in the U.S., where most of their studies’ trial sites are. But emerging variants pose a looming problem that may lead them and other companies to develop new mAbs, or new combinations of existing mAbs.