Monoclonal antibodies targeting Covid-19 have high potential, but ability to tackle new SARS-CoV-2 variants remains muddled

GlobalData Healthcare 29 March 2021 (Last Updated March 29th, 2021 11:29)

The emergence of new SARS-CoV-2 variants has been detected in over 40 countries and is disrupting drug development worldwide. The prevalence of these more transmissible strains is growing fast and may require adjustments to current Covid-19 therapies to ensure they retain clinical efficacy.

Monoclonal antibodies targeting Covid-19 have high potential, but ability to tackle new SARS-CoV-2 variants remains muddled
The emergence of new SARS-CoV-2 variants may require adjustments to current Covid-19 therapies. Credit: Cryptographer / Shutterstock.

The emergence of new SARS-CoV-2 variants has been detected in over 40 countries and is disrupting drug development worldwide. The prevalence of these more transmissible strains is growing fast and may require adjustments to current Covid-19 therapies to ensure they retain clinical efficacy. Variants of concern include B.1.1.7 from the UK, B.1.351 from South Africa and P.1 from Brazil.

The strains are associated with an increase of around 50% in transmission, while B.1.351 and P.1 are also linked to decreased neutralisation by monoclonal antibodies (mAbs) and lower post-vaccination immunity. Covid-19 vaccine rollouts are, fortunately, expanding, with 110,978,514 people already fully vaccinated worldwide. This is likely to significantly limit the use of mAbs for treating Covid-19, leaving Regeneron and Eli Lilly to compete in a smaller, more challenging market.

Recent data show that the South African variant can escape from most mAb therapies. It also completely evades neutralising antibodies in convalescent plasma derived from patients who were previously infected with the original SARS-CoV-2 strain. Experts believe this B.1.351 variant is more heavily mutated than the UK B.1.1.7 strain and will be more difficult to contain. B.1.1.7 is currently the most prevalent variant in the US, with over 7,500 cases reported. The B.1.351 variant has 219 reported cases, while P.1 lags behind with 61.

Regeneron and Eli Lilly have both been granted an Emergency Use Authorisation (EUA) for mAbs against Covid-19. According to recent data, Lilly’s single mAb (bamlanivimab) is not effective against variants and will no longer be used in the US, while the combination therapy bamlanivimab + etesevimab is slightly better, with potency detected against B.1.1.7. Regeneron’s mAb combination therapy casirivimab + imdevimab, however, has been proven to be the most effective against the emerging variants of concern.

Top-line third-phase trial data for Regeneron’s antibody cocktail REGEN-COV (casirivimab + imdevimab) was positive, meeting its primary endpoint by reducing the risk of hospitalisation or death by 70% compared to placebo. REGEN-COV also met all secondary endpoints, which included reducing the duration of symptoms by four days. With an EUA already granted in the US, Regeneron plans to submit a Biologics License Application, including this most recent third-phase data. FDA updates also indicate that REGEN-COV is the only mAb therapy that has retained potency against these emerging strains.

Eli Lilly’s mAbs, bamlanivimab and etesevimab, will likely stumble in attempts to gain full FDA approval, given the antiviral resistance observed in B.1.351, P.1. and the New York variant B.1.526. This mAb combination, however, may yet prove effective against the B.1.1.7 variant.

More data is required for all potential and current Covid-19 therapies due to the rapid spread of variant strains. While mAb treatments will likely be more scrutinised due to their specific targets, vaccine development also needs to be reassessed to determine efficacy and durability across the various platforms.