Investigators tested bamlanivimab monotherapy as well as in combination with etesevimab.
Bamlanivimab combination therapy with etesevimab can reduce the viral load of novel coronavirus (COVID-19) by Day 11, according to a paper published in JAMA.
Investigators from across the US reported the results of the phase 2 portion of their randomized Phase 2/3 trial, which aimed to determine the effect of bamlanivimab alone and bamlanivimab in combination with etesevimab as a treatment for mild to moderate COVID-19. Across 49 centers in the US, 533 patients who tested positive for COVID-19 and had 1 or more mild to moderate symptom were included in the analysis.
The patients enrolled in the first wave, which took place from June to August 2020, received bamlanivimab alone in a single infusion of 700 mg, 2800 mg, 7000 mg, or placebo. Patients enrolled in the second wave, from August to September 2020, received bamlanivimab combined with etesevimab (2800 mg bamlanivimab and 2800 mg etesevimab) or placebo.
The investigators then measured change in COVID-19 viral load at about day 11, in addition to measuring change in symptom score at days 7, 11, 15, and 22, time to symptom improvement, time to symptom resolution, the proportion of patients showing symptom improvement, and the proportion of patients with COVID-19-related hospitalization, emergency department visit, or death by day 29. The investigators used a self-rating questionnaire to assess symptom severity, including cough, shortness of breath, fever, fatigue, body aches and pain, sore throat, chills, and headache.
By day 11, the study authors said the change in log viral load from baseline was -3.72 for the 700 mg group, -4.08 for the 2800 mg group, -3.49 for the 7000 mg group, -4.37 for the combination therapy group, and -3.80 for the placebo group. They said that change in log viral load therefore was not significantly different for any of the monotherapy groups compared to placebo, but the combination therapy group showed a statistically significant difference.
Change in mean total symptom score from baseline to day 11 was different for the 700 mg monotherapy group and the combination group compared to placebo, but the difference wasn’t statistically difference for the 2800 mg monotherapy group or the 7000 mg group, the study authors said. Additionally, change in symptom improvement by day 11 was scattered as well among the groups. For example, it was statistically different for the 700 mg group and the 7000 mg group, but not in the 2800 mg group or the combination treatment group, the study authors learned.
The investigators noted that the proportion of patients with COVID-19-related hospitalizations or emergency department visits by Day 29 was 1.0 percent for the 700 mg group, 1.9 percent for the 2800 mg group, 2.0 percent for the 7000 mg group, and 0.9 percent for the combination therapy group. In the placebo group, the proportion was 5.8 percent (9 events out of 156 patients).
There were no serious adverse events in the bamlanivimab monotherapy groups and in just 1 of 112 patients in the bamlanivimab and etesevimab combination therapy group (urinary tract infection unrelated to the study drug), the study authors said. There was 1 serious adverse event in the placebo group (upper abdominal pain, also unrelated to the study drug).
The most frequently reported adverse event was nausea and diarrhea across all groups. There were immediate hypersensitivity reactions observed in the all groups, which may have been related to the infusion, the study authors also said. Most reactions occurred during infusion and were mild.
“Recently, the 700 mg dose of bamlanivimab has been authorized for emergency use in the US and Canada for the treatment of outpatients with mild to moderate COVID-19,” the study authors concluded. “Treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11; no significant difference in viral load reduction was observed for bamlanivimab monotherapy.”