Testing 2 Monoclonal Antibodies to Treat COVID-19 Symptoms

Using the monoclonal antibodies tixagevimab and cilgavimab (AstraZeneca’s Evusheld) was safe but had no significant impact on COVID-19 symptoms, according to a paper published in JAMA Network Open.

Investigators primarily based in the US conducted a pair of phase 2 randomized clinical trials to determine if the long-acting COVID-19 monoclonal antibodies tixagevimab and cilgavimab given in combination improve COVID-19 symptoms and viral shedding when administered. The patients were adults aged 18 years or older who were not hospitalized but had a positive COVID-19 test and presented symptoms between February 1-May 31, 2021.

In the first study, there were 229 participants randomized to receive either 600 mg of tixagevimab and cilgavimab (300 mg each) given intramuscularly in the lateral thigh, or a placebo. Half of the participants in this study were men, most participants were white, and the median age was 39 years. After the patients received either the drug or placebo, they completed a daily symptom diary through day 28 and collected daily self-nasal swabs through day 14. Additionally, the patients returned to the clinic for assessments on days 3, 7, 14, and 28 for staff-collected nasopharyngeal swabs.

Time to symptom improvement in the intramuscular study did not differ significantly between the intervention and placebo arms at 8 and 10 days, respectively. The median time to return to health was also not significantly different at 14 and 13 days, respectively. There were no deaths in either study arm, though 4 participants were hospitalized in the intervention group and 7 patients were hospitalized in the placebo group in the first 28 days.

In the second study, 119 participants were randomized to receive either 300 mg of tixagevimab and cilgavimab (150 mg each) given intravenously or a placebo. The median age of the participants was 44 years, about 60% of this group of participants were women, and most reported white ethnicity. The participants in this group had the same follow up (daily self-swabs, symptom diary, clinical visits) as the intramuscular group.

Again, time to symptom improvement was similar between the groups with the intravenous group needing 11 days and the placebo group needing 10 days, the study authors reported. The median time to return to heath was similar again, requiring 12 and 15 days, respectively. No deaths and no hospitalizations were reported in the intravenous study in the first 28 days.

The study authors found that a greater proportion of intramuscular participants who received the intervention compared to placebo had COVID-19 RNA below the lower limit of quantification (LLOQ) at day 7, but not at days 3 or 14. There were no differences in the proportion below LLOQ observed in the intravenous intervention compared to placebo group at any of the time points.

Notably, just 13 participants in the intramuscular trial and 1 participant in the intravenous trial reported receiving at least 1 COVID-19 dose prior to enrollment. They also noted, these 2 trials were conducted prior to the Delta and Omicron COVID-19 variant surges.

“Results of these 2 randomized clinical trials indicate that tixagevimab-cilgavimab administered intramuscularly to the thigh was safe but neither intramuscular nor intravenous treatment had significant effects on measured symptom outcomes,” the study authors concluded. “An antiviral effect of tixagevimab-cilgavimab was demonstrated in the primary virologic analysis for intramuscular and other analyses in the truncated intravenous study. There were numerically fewer hospitalizations with receipt of tixagevimab-cilgavimab.”