Discussion
tixagevimab-cilgavimab
DISEASE PROGRESSION, SECONDARY
In these 2 phase 2 randomized clinical trials conducted prior to the emergence of the SARS-CoV-2 Delta and Omicron variants in a predominantly unvaccinated population with a median symptom duration of 6 days at the time of treatment, a single 600-mg IM dose of tixagevimab-cilgavimab to the thigh was safe but did not lead to improvement in symptom outcomes among adult outpatients with mild-to-moderate COVID-19 compared with placebo. Within the smaller group administered a 300-mg IV dose of tixagevimab-cilgavimab or placebo, there was a similar absence of benefit on symptoms. However, an antiviral effect of tixagevimab-cilgavimab is supported by the primary virologic analysis in the IM group and in secondary and post hoc analyses of both groups. There were fewer hospitalizations in both IM and IV T-C arms compared with placebo arms, but the study had limited power to evaluate effects.Intramuscular tixagevimab-cilgavimab administered in the vastus lateralis muscle of the thigh was safe and well-tolerated. Absorption of drugs administered to the thigh is expected to be quicker with less interperson variability compared with injection into gluteal musculature, especially in women and those with higher body mass index.The virologic findings from this study complement those from the placebo-controlled phase 3 TACKLE trial of gluteal IM administration of tixagevimab-cilgavimab,We found a significant decline in SARS-CoV-2 RNA from baseline to day 3 in the post hoc analysis for IV but not IM tixagevimab-cilgavimab compared with placebo. It is possible the more rapid achievement of effective mAb concentrations with IV compared with IM administration could also provide greater protection from disease progression, depending on the timing of treatment. Drugs with demonstrated antiviral effect have consistently shown effect on hospitalizations, while clinical benefits have also been observed in the absence of effect on nasopharyngeal RNA.