Lilly and GSK/Vir antibody pairing offers resistant COVID-19 hope

Two antibodies targeting different parts of the COVID-19 virus spike protein, from Eli Lilly and GlaxoSmithKline/Vir Biotech, can cut viral load dramatically within a week. 

The BLAZE-4 trial found that co-administration of Lilly’s bamlanivimab – already granted emergency approval as a COVID-19 treatment – and GSK/Vir’s experimental antibody VIR-7831 reduced virus levels by 70% after seven days compared to placebo in people with mild or moderate COVID-19 symptoms.

The combination did better than bamlanivimab given alone, according to the data, which comes after the US opted to stop using Lilly’s antibody as a monotherapy due to the surge in coronavirus variants in circulation that might have resistance to the drug.

Bamlanivimab can still be used in the US in combination with Lilly’s other COVID-19 antibody etesevimab, but with new variants of SARS-CoV-2 being discovered at an alarming rate having multiple combinations available could be important.

Bamlanivimab and VIR-7831 (also known as GSK4182136) target different regions of the SARS-CoV-2 spike protein, and the hope is that will boost potency and make the virus less able to evade neutralisation.

Backing up that hypothesis, bamlanivimab/VIR-7831 seems to be slightly better at reducing viral load at day seven than bamlanivimab/etesevimab was at day 11 in the BLAZE-1 study, which showed a 67% reduction.

That comes the usual caveats about comparing data from different studies, and particularly as the data from BLAZE-4 is preliminary and comes from an interim readout before the data are mature.

The new study also wasn’t able to show an effect of bamlanivimab/VIR-7831 on the secondary endpoint of hospitalisation rates, as no patient in either group had to be admitted to hospital at the data cut-off.

Lilly’s chief scientific officer Daniel Skovronsky said however that reducing high viral load has been shown to be “strongly correlated with the clinical outcome of COVID-19 related hospitalisations and deaths in high-risk patients”.

That has been shown in the BLAZE-1 trial with bamlanivimab/etesevimab, as well as with VIR-7831 on its own in the COMET-ICE study.

With vaccination rates climbing the need for antibody therapies may be diminishing, but it is always possible that variants will emerge that will cause breakthrough disease, and new drugs required to prevent patients developing severe COVID-19.

“Recent preclinical data suggest that VIR-7831 maintains activity against current circulating variants of concern,” said Vir chief executive George Scangos. In contrast, there is preliminary evidence that resistance is emerging to bamlanivimab.

“Now, with these exciting new data from the BLAZE-4 trial, we believe that VIR-7831 has an important role to play as both monotherapy and in combination with other [antibodies],” he added.

GSK and Vir say they are discussing emergency use authorisation of VIR-7831 with the EMA and other regulators, including possible co-administration with bamlanivimab.

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