• Otávio Santiago

‘Super-antibodies’ could curb COVID-19 and help avert future pandemics

According to analysts and researchers alike, so-called super-antibodies such as sotrovimab should have an edge over first-generation monoclonal antibody (mAb) therapies for COVID-19 because of their broad neutralization capacity in the face of emerging virus variants. “Physicians aren’t going to sequence what version of the virus people have, so they’ll go for the antibodies that have the higher barrier to resistance or the ones that work on [known] variants,” says Phil Nadeau, an analyst at Cowen.

The antibody therapy from Vir Biotechnology and GlaxoSmithKline, a recombinant human immunoglobulin G1 mAb, is now the third mAb-based treatment marketed for individuals with mild-to-moderate COVID-19 who are at high risk for progression to severe disease. (Eli Lilly and Regeneron each have a two-mAb cocktail with EUAs for the same indication.) And although sales opportunities should diminish for all these products as vaccination rates increase worldwide, Nadeau anticipates there will be a sustained market for COVID-19 mAbs to help treat individuals who, for medical reasons, can’t mount an appropriate immune response to vaccination or, for whatever reason, elect not to get the shot.

According to his models, sotrovimab should capture around 10% of the $3 billion global COVID-19 mAb market this year, rising to 30% of the $1.67 billion market in 2022.

Other broadly cross-reactive mAbs could soon be jockeying for market share as well, as investment money flows in to rush some of the leading candidates through late-stage clinical development. In April, for example, Adagio Therapeutics raised $336 million (on top of the $130 million war chest it amassed last year) to bankroll large-scale trials of ADG20, an mAb now being evaluated for use as a therapy and for prevention. Startups such as Centivax, Corat Therapeutics, IDBiologics, Leyden Labs, Memo Therapeutics and SpikImm are working on next-generation mAbs for COVID-19 as well.

Sotrovimab traces its roots back to blood drawn in 2013 from an individual who had recovered from the 2003 outbreak of severe acute respiratory syndrome (SARS); ADG20 has a similar origin story, while most other clinical-stage mAbs were inspired by antibodies found in more recent COVID-19 survivors. Many companies then optimized their mAbs by extending half-lives, enhancing neutralizing activity, manipulating constant region (Fc)-mediated effector functions, or applying some combination of these engineering strategies.

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