Effect of Bamlanivimab as Monotherapy or in Combination With Etesevimab on Viral Load in Patients With Mild to Moderate COVID-19

Abstract

IMPORTANCE Coronavirus disease 2019 continues to spread rapidly worldwide. Neutralizing antibodies are a potential treatment for COVID-19.OBJECTIVE To determine the effect of bamlanivimab monotherapy and combination therapy with bamlanivimab and etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe BLAZE-1 study is a randomized phase 2/3 trial at 49 US centers including ambulatory patients (N = 613) who tested positive for SARS-CoV-2 infection and had 1 or more mild to moderate symptoms. Patients who received bamlanivimab monotherapy or placebo were enrolled first (June 17-August 21, 2020) followed by patients who received bamlanivimab and etesevimab or placebo (August 22-September 3). These are the final analyses and represent findings through October 6, 2020. INTERVENTIONS Patients were randomized to receive a single infusion of bamlanivimab (700 mg [n = 101], 2800 mg [n = 107], or 7000 mg [n = 101]), the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab [n = 112]), or placebo (n = 156). MAIN OUTCOMES AND MEASURES The primary end point was change in SARS-CoV-2 log viral load at day 11 (±4 days). Nine prespecified secondary outcome measures were evaluated with comparisons between each treatment group and placebo, and included 3 other measures of viral load, 5 on symptoms, and 1 measure of clinical outcome (the proportion of patients with a COVID-19-related hospitalization, an emergency department [ED] visit, or death at day 29).RESULTS Among the 577 patients who were randomized and received an infusion (mean age, 44.7 [SD, 15.7] years; 315 [54.6%] women), 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was -3.72 for 700 mg, -4.08 for 2800 mg, -3.49for7000mg,-4.37forcombinationtreatment,and-3.80forplacebo.Comparedwithplacebo, the differences in the change in log viral load at day 11 were 0.09 (95% CI, -0.35 to 0.52; P = .69)for 700 mg, -0.27 (95% CI, -0.71 to 0.16; P = .21) for 2800 mg, 0.31 (95% CI, -0.13 to 0.76; P = .16) for 7000 mg, and -0.57 (95% CI, -1.00 to -0.14; P = .01) for combination treatment. Among the secondary outcome measures, differences between each treatment group vs the placebo group werestatisticallysignificantfor10of84endpoints.TheproportionofpatientswithCOVID-19-related hospitalizationsorEDvisitswas5.8%(9events)forplacebo,1.0%(1event)for700mg,1.9%(2events) for 2800 mg, 2.0% (2 events) for 7000 mg, and 0.9% (1 event) for combination treatment. Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment.CONCLUSIONS AND RELEVANCE Among nonhospitalized patients with mild to moderate COVID-19 illness, 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...

Monoclonal antibodies for treating COVID-19

“…The final analysis for the BLAZE-1 study included a fourth treatment arm that used the combination of bamlanivimab and etesevimab 2800 mg/2800 mg. 8 Results were similar to the interim analysis with no significant differences compared with placebo. The bamlanivimab-etesevimab group hospitalization or emergency department rate was 0.9% (1 of 109 patients) compared to placebo at 5.8% (9 of 152 patients, P = .049).…”

Impact of monoclonal antibody treatment on hospitalization and mortality among non-hospitalized adults with SARS-CoV-2 infection

“…17 A post hoc analysis in BLAZE-1 of those 65 or older or with BMI of 35 kg/m 2 or greater demonstrated a larger numerical benefit, 2.7% vs 13.5%. 3 In this report of our experience, we identified a similar association between bamlanvimab monotherapy and hospitalization or mortality in a propensity matched analysis with an OR of 0.31, or a 69% lower odds of hospitalization or mortality.…”

“…Our observational study suggests a benefit of mAb treatment in reducing the risk of COVID-19 complications for patients at higher risk of severe disease. Initial reports of bamlanivimab 700 mg in outpatients showed improvement of symptoms at day 11 for the entire study population 3 and numerically fewer hospitalizations and ED visits at day 29 (1.6% vs 6.3%). 17 A post hoc analysis in BLAZE-1 of those 65 or older or with BMI of 35 kg/m 2 or greater demonstrated a larger numerical benefit, 2.7% vs 13.5%.…”

“…Several clinical trials currently evaluate mAbs for prevention or treatment of COVID-19; however, real-world data are limited, and the role of mAbs for patients with COVID-19 remains controversial. 3, 5…”

Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Ambulatory Patients with Early COVID-19

“…Early clinical trial data suggest that the efficacy of combination monoclonal antibodies targeting multiple, non-overlapping epitopes may be superior to monovalent products. 4 Differential activity against emerging variant SARS-CoV2 strains may also play a role. In contrast to casirivimab/imdevimab, bamlanivimab may exhibit reduced activity against the E484 17 mutation found in the B.1.351, P.1 and B.1.526 strains and perhaps the L452 mutation found in the B.1.149 California variant.…”