Evusheld (tixagevimab + cilgavimab) failed to improve outcomes in a phase III trial involving hospitalised COVID-19 patients

Evusheld was given to 214 of the 399 participants in the DISCOVERY study and did not offer substantial improvement in clinical status or expedite viral clearance in these patients. Despite this, the drug was found to cause a substantial increase in neutralising antibodies against SARS-CoV-2 at days three and eight. Although no major safety events or increased cardiovascular risks were recorded, the trial found no significant differences in mortality or hospital admission rates between those who received Evusheld and those given standard care.

The mortality rate at day 90 was around 15% for both the control arm and the cases.

Researchers speculate that different Covid-19 variants present in the trials could have caused the discrepancy between the results of the DISCOVERY trial and the prior ACTIV-3-TICO study, which showed a decline in mortality at day 15. In the DISCOVERY trial, 40% of infections were caused by the Omicron variant, whereas the ACTIV trial occurred primarily during the prevalence of the Delta variant. The Omicron variant’s ability to evade Covid-19 vaccines and therapeutic monoclonal antibodies (mABs) has been noted as more pronounced than that of the original strain or Delta variant.

Evusheld is a combination of two long-acting antibodies, tixagevimab (AZD8895) and cilgavimab (AZD1061).