Antibody Combo Evusheld Fails to show Impressive results in COVID-19 Trial
In the Phase 3 DISCOVERY European trial, although there was a considerable rise in neutralizing antibodies against SARS-CoV-2 at days 3 and 8, Evusheld monoclonal antibody combination drug failed to exhibit significant improvements in the clinical status of hospitalized COVID-19 patients or accelerated viral clearance.
The findings of this clinical trial were reported in a research letter published in the Journal of Infection. The trial involved 399 participants, 214 of whom were administered Evusheld, a combination of tixagevimab and cilgavimab (T-C) monoclonal antibodies (mABs).
A previous study, ACTIV-3-TICO, showed a significant reduction in mortality at day 15 in patients who received Evusheld as an intramuscular injection.
In the current trial, no significant differences in mortality or hospitalization were observed between the participants who were administered Evusheld and those who received standard care (not remdesivir) despite the absence of any major safety events or increased cardiovascular risks, as reported by researchers.
The ACTIV-3-TICO trial primarily enrolled participants infected with the Delta variant, while the DisCoVeRy trial had a substantially higher proportion of patients infected with the Omicron variant, at 40%. Despite the Omicron variant's greater evasiveness to vaccines and therapeutic monoclonal antibodies, including T-C, as demonstrated by in-vitro neutralization assays, it is generally considered less virulent than prior variants, such as Delta. However, the high mortality rate of 15% observed at day 90 in our trial and the significant morbidity described by Kamboj et al. highlight that many patients who did require hospitalization were still at risk of dying, they said.
According to the researchers, the discrepancy observed between the ACTIV trial and DISCOVERY may be attributed to the presence of variants. Notably, the Omicron variant caused 40% of COVID-19 infections in the DISCOVERY trial, whereas the ACTIV trial occurred primarily during the Delta variant's prevalence.
In the ambulatory setting, when ancestral strains of the virus were circulating, a study called TACKLE found that administering intramuscular T-C to treat SARS-CoV-2 infections significantly reduced the likelihood of hospitalization and death in high-risk patients compared to a placebo.
The Omicron variant of SARS-CoV-2 and its various sub-lineages have demonstrated a greater ability to evade vaccines and therapeutic monoclonal antibodies (mABs), such as T-C, compared to the ancestral strain or Delta variant.
Reference:
Maya Hites et al. Tixagevimab-cilgavimab (AZD7442) for treating patients hospitalized with COVID-19 (DisCoVeRy): a phase 3, randomized, double-blind, placebo-controlled trial. Journal of Infection. Published: February 15, 2024
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