
Despite a substantial increase in neutralizing antibodies against SARS-CoV-2 at days 3 and 8, the monoclonal antibody combination drug Evusheld did not significantly improve hospitalized COVID-19 patients' clinical status or accelerate viral clearance in a phase 3 DISCOVERY European trial.
The results of the trial were described yesterday in a research letter in the Journal of Infection. Evusheld is composed of tixagevimab and cilgavimab (T-C) monoclonal antibodies (mABs), and the study included 399 participants, 214 of whom received Evusheld. A previous study, ACTIV-3-TICO, showed a significant reduction in mortality at day 15 in patients who received Evusheld as an intramuscular injection.
Though there were no major safety events and no increased cardiovascular risks seen in the present trial, researchers found no significant differences in mortality or hospitalization among participants randomized to receive Evusheld and those who received standard care (not remdesivir).
Study conducted during Omicron
Both controls and cases in the trial had an approximate mortality rate of 15% at day 90.
The researchers said the difference seen between the ACTIV trial and DISCOVERY may be due to variants: 40% of COVID infections in the DISCOVERY trial were caused by the Omicron variant, compared to the ACTIV trial, which was primarily during Delta variant dominance.
The SARS-CoV-2 Omicron variant and its multiple sub-lineages have proven to be more evasive than the ancestral strain or Delta variant to vaccines and therapeutic mABs.
"In the ambulatory setting, and while ancestral strains were circulating, the administration of intramuscular T-C to treat SARS-CoV-2 infections significantly reduced the risk of hospitalization and death in patients at risk for disease progression, compared to placebo," the authors wrote, referring to yet another phase 3 trial, called TACKLE. "The SARS-CoV-2 Omicron variant and its multiple sub-lineages have proven to be more evasive than the ancestral strain or Delta variant to vaccines and therapeutic mABs, including T-C."