Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: A randomized clinical trial

Robert L. Gottlieb, Ajay Nirula, Peter Chen, Joseph Boscia, Barry Heller, Jason Morris, Gregory Huhn, Jose Cardona, Bharat Mocherla, Valentina Stosor, Imad Shawa, Princy Kumar, Andrew C. Adams, Jacob Van Naarden, Kenneth L. Custer, Michael Durante, Gerard Oakley, Andrew E. Schade, Timothy R. Holzer, Philip J. EbertRichard E. Higgs, Nicole L. Kallewaard, Janelle Sabo, Dipak R. Patel, Paul Klekotka, Lei Shen, Daniel M. Skovronsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

IMPORTANCE Coronavirus disease 2019 (COVID-19) 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 PARTICIPANTS The 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 placebowere 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 Patientswere randomized to receive a single infusion of bamlanivimab (700mg [n = 101], 2800mg [n = 107], or 7000mg [n = 101]), the combination treatment (2800mg of bamlanivimab and 2800mg of etesevimab [n = 112]), or placebo (n = 156). MAIN OUTCOMES AND MEASURES The primary end pointwas 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 patientswhowere 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 11was -3.72 for 700mg, -4.08for2800mg, -3.49for7000mg,-4.37forcombinationtreatment,and-3.80forplacebo.Comparedwithplacebo, the differences in thechangein log viral load atday 11were0.09(95%CI,-0.35 to0.52;P = .69)for 700mg, -0.27 (95%CI, -0.71 to0.16; P = .21) for2800mg,0.31 (95%CI, -0.13 to0.76; P = .16) for 7000mg, and -0.57 (95%CI, -1.00to -0.14; P = .01) for combination treatment.Among the secondary outcome measures, differences between each treatment group vs the placebo group werestatistically significant for10of84endpoints.TheproportionofpatientswithCOVID-19-related hospitalizationsorEDvisitswas5.8%(9events)forplacebo, 1.0%(1event)for700mg,1.9%(2events) for2800mg, 2.0%(2 events) for 7000mg, and0.9%(1 event) for combination treatment. Immediatehypersensitivity reactionswere reported in9patients (6 bamlanivimab,2combination treatment, and 1 placebo).Nodeaths 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 reduction was observed for bamlanivimab monotherapy. Further ongoing clinical trials will focus on assessing the clinical benefit of antispike neutralizing antibodies in patients with COVID-19 as a primary end point.

Original languageEnglish (US)
Pages (from-to)632-644
Number of pages13
JournalJAMA - Journal of the American Medical Association
Volume325
Issue number7
DOIs
StatePublished - Feb 16 2021

ASJC Scopus subject areas

  • Medicine(all)

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