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Bamlanivimab Alone vs. With Etesevimab on Viral Load in Mild-Moderate COVID-19
Quick Takes
- Bamlanivimab and etesevimab are potent antispike neutralizing monoclonal antibodies that were derived from two separate patients who recovered from COVID-19.
- Combination therapy bamlanivimab and etesevimab was associated with a reduction in viral load at day 11 in outpatients with mild COVID-19.
- Bamlanivimab and etesevimab were safe and well tolerated. Their clinical efficacy remains to be proven.
Study Questions:
What is the impact of bamlanivimab with or without etesevimab on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load in mild to moderate coronavirus 2019 (COVID-19)?
Methods:
The BLAZE-1 study is a two-part randomized phase 2/3 trial at 49 US centers, which included 533 adult outpatients (mean age 45 years, 55% women, 43% Hispanic, and 67% with ≥1 risk factor for severe COVID-19) who tested positive for SARS-CoV-2 infection and had ≥1 mild to moderate symptoms. In the first part of the trial, patients enrolled from June 17–August 21, 2020 (n = 309) were randomized to bamlanivimab (at different doses) or placebo. In the second part (August 22–September 3), patients (n = 268) received either combination bamlanivimab and etesevimab or placebo. Randomization was stratified by symptom duration (≤8 days and >8 days). Treatment was administered within 3 days of the positive SARS-CoV-2 test. The primary endpoint was change in SARS-CoV-2 log viral load at day 11 (±4 days). Clinical outcomes and symptoms were also compared.
Results:
The change in log viral load from baseline at day 11 was –3.72 for 700 mg, –4.08 for 2800 mg, –3.49 for 7000 mg, –4.37 for combination treatment, and –3.80 for placebo. Only combination therapy was associated with a more significant decrease in viral load compared to placebo (–0.57; 95% confidence interval [CI], –1.00 to –0.14; p = 0.01) for combination treatment. Viral clearance (defined as two consecutive negative test results for SARS-CoV-2) did not differ among any of the treatment groups at any time point. Interestingly, symptoms were significantly improved only in the 700 mg bamlanivimab group. The combination treatment group had a significantly lower proportion of COVID-19–related hospitalizations or emergency department visits (–4.9%; 95% CI, –8.9% to –0.8%; p = 0.049). Serious adverse events unrelated to SARS-CoV-2 infection or considered related to the study drug occurred in 0% (0/309) of patients in the bamlanivimab monotherapy groups, in 0.9% (1/112) of patients in the bamlanivimab and etesevimab combination group, and in 0.6% (1/156) of patients in the placebo group.
Conclusions:
Treatment with bamlanivimab and etesevimab, compared with placebo, was associated with a statistically significant reduction in SARS-CoV-2 viral load at day 11.
Perspective:
Bamlanivimab (also known as LY3819253 or LY-CoV555) and etesevimab (LY3832479 or LY-CoV016) are antispike neutralizing monoclonal antibodies that were derived from two separate patients who recovered from COVID-19 in North America and China. They bind to the receptor binding domain of the spike protein of SARS-CoV-2, blocking the spike protein’s attachment to the human ACE2 receptor. The Food and Drug Administration (FDA) issued an emergency use authorization for the use of bamlanivimab in the treatment of outpatients with mild to moderate COVID-19 at risk for progressing to severe COVID-19 based on an interim analysis of the BLAZE-1 trial that showed a significant reduction in the secondary endpoint of hospitalization for COVID-19. This study represents an analysis of the final dataset of BLAZE-1, which interestingly no longer shows a statistically significant difference in the reduction of hospitalizations, except in the combination therapy group. BLAZE-1 was not powered to detect differences in clinical outcomes, and these findings remain preliminary at best—as highlighted by the differing conclusions of this analysis compared to the initial one. Until adequately powered clinical trials show evidence of efficacy, routine use of these monoclonal antibodies should be re-evaluated.
Clinical Topics: COVID-19 Hub, Prevention, Novel Agents
Keywords: Antibodies, Monoclonal, Coronavirus, COVID-19, Emergency Service, Hospital, Outpatients, Pharmaceutical Preparations, Primary Prevention, Risk Factors, Severe Acute Respiratory Syndrome, Spike Glycoprotein, Coronavirus, Viral Load
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