Eli Lilly/AbCellera’s COVID-19 variant-targeting antibody enters clinical trials

An antibody targeting variants of COVID-19, developed as part of a collaboration between Eli Lilly and Canadian biotech company AbCellera, has entered clinical trials.

The antibody – LY-CoV1404 – will be evaluated in patients with mild-to-moderate COVID-19, and will be studied alone and together with other monoclonal antibodies (mAb) in the expanded BLAZE-4 trial.

The progression into clinical trials is supported by preclinical data released by AbCellera, which showed that LY-CoV1404 binds to a ‘rarely mutated region’ of the SARS-CoV-2 spike protein.

This data also demonstrated that the mAb can neutralise all currently known variants of concern, including ones identified in the UK (B.1.1.7), South Africa (B.1.351), Brazil (P.1), California (B.1.426 and B.1.429) and New York (B.1.526).

AbCellera added that LY-CoV1404 is ‘substantially more potent’ in viral neutralisation assays when compared to other broadly neutralising antibodies.

“The ability of SARS-CoV-2 variants to negatively alter the trajectory of the pandemic emphasises the essential need for antibody therapies that can be developed in real time to combat the virus as it evolves,” said Bo Barnhart, scientific director at AbCellera.

“LY-CoV1404’s powerful neutralisation of SARS-CoV-2 allows for exploration of lower clinical doses, which may support subcutaneous administration and availability of more doses to treat patients around the world,” he added.

The need for antibodies that combat variants of concern is growing substantially, especially since Lilly discontinued its other AbCellera-partnered mAb bamlanivimab when administered alone.

In April, the US Food and Drug Administration (FDA) revoked the emergency use authorisation (EUA) for bamlanivimab monotherapy following concerns that COVID-19 variants may be resistant against the mAb when administered alone.

However, a combination of bamlanivimab and etesevimab still retains an EUA for the treatment of mild-to-moderate COVID-19 in high-risk adults and paediatric patients aged 12 years and older weighing at least 40kg.

“While the risk-benefit assessment for using bamlanivimab alone is no longer favourable due to the increased frequency of resistant variants, other monoclonal antibody therapies authorised for emergency use remain appropriate treatment choices when used in accordance with the authorised labelling and can help keep high risk patients with COVID-19 out of the hospital,” said Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research.