Vulnerability of COVID-19 mAbs to emerging variants: Data Byte
Lilly’s mAbs hit hardest, while a Vir mAb that was designed to work across coronavirus species ranks among the least affected
Lilly’s mAbs are the hardest hit by two COVID-19 variants, while Vir’s mAb, which targets epitopes conserved across coronaviruses, ranks among the least affected.
Data on the vulnerability of mAbs to emerging SARS-CoV-2 variants supports the hypothesis that antibodies that bind epitopes conserved across coronavirus species will be most resilient to mutations.
Recent studies on neutralizing mAb potencies against emerging variants suggest that products from Vir Biotechnology Inc. (NASDAQ:VIR) and Regeneron Pharmaceuticals Inc. (NASDAQ:REGN) are among the least vulnerable to the mutants, while mAbs from Eli Lilly and Co. (NYSE:LLY) and its partners are the most likely to lose efficacy.
Early on, Vir set out to target epitopes shared between SARS-CoV-1 and SARS-CoV-2, banking on the idea that such sites would be unlikely to change when the virus mutates.
A paper published Tuesday in bioRxiv by Columbia University researchers, collaborating with Regeneron and NIAID, showed that S309, a precursor to VIR-7831 and VIR-7832 from Vir, was unaffected in pseudovirus assays incorporating spike mutations from the B.1.351 variant, first identified in South Africa; and only 3.1 times less potent in assays incorporating the mutations from the B.1.1.7 variant, first identified in the U.K., versus the prevalent single mutation D614G.
Regeneron took a different approach, leaning on the promise of combinations to prevent escape mutations.
According to the study’s authors, Regeneron’s REGEN-COV (casirivimab/imdevimab) was “seemingly unaffected” by the mutations in both variants, even though casirivimab on its own had a 58.8-fold drop in potency against B.1.351. The company said Wednesday it independently confirmed the findings. The cocktail has an EUA to treat high-risk outpatients.
A Regeneron spokesperson told BioCentury the company is continuing to test its mAbs against new mutations in vitro, and has multiple neutralizing antibody candidates that it is considering for future combinations if necessary.
One combination — bamlanivimab plus the precursor to etesevimab — fared less well against the variants.
Lilly is developing bamlanivimab, which has an EUA from FDA as a monotherapy, with AbCellera Biologics Inc. (NASDAQ:ABCL); and etesivimab with Shanghai Junshi Biosciences Co. Ltd. (HKEX:1877; Shanghai:688180), respectively.
Separately on Wednesday, Lilly, Vir and GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) announced they would combine bamlanivimab with VIR-7831 to address emerging SARS-CoV-2 variants. The new cocktail is under evaluation in the Phase II BLAZE-4 study to treat low-risk COVID-19 outpatients.
Regulators have yet to disclose how they will approach expanding EUAs and approvals to accommodate new mAb cocktails to address new variants.
In a tweet on Monday, Acting FDA Commissioner Janet Woodcock said the agency is considering regulatory pathways for authorized COVID-19 vaccines or other products that would require changes in response to emerging variants.