BACKGROUND AND PURPOSE:

• Bamlanivimab and etesevimab are both antispike neutralizing monoclonal antibody treatments granted emergency use authorization as treatments for COVID-19
• Gottlieb et al. (JAMA, 2021) examined the effect of bamlanivimab, and combination therapy with bamlanivimab and etesevimab in patients with mild to moderate COVID-19

METHODS:

• Randomized phase 2/3 trial
  • BLAZE-1 (Blocking Viral Attachment and Cell Entry with SARS-CoV-2 Neutralizing Antibodies) Trial
• Setting
  • 49 US centers
• Participants
  • Ambulatory patients who tested positive for SARS-CoV-2 and had one or more mild to moderate symptoms
• Interventions
  • Bamlanivimab therapy only
    • Single infusion of either
      • 700 mg
      • 2800 mg
      • 7000 mg
  • Combination therapy
    • 2800 mg of bamlanivimab and 2800 mg of etesevimab
  • Placebo
• Primary outcomes
  • Change in SARS-CoV-2 log viral load at day 11 (±4 days)
• Secondary outcomes
  • Other measures of viral load
  • Symptoms
  • Clinical outcomes: Hospitalization, emergency department visit, or death)

RESULTS:

• 533 patients completed evaluation
  • Mean (SD) age: 44.7 (15.7) years
  • 54.6% women
  • Bamlanivimab group: 309 participants (distributed evenly between dosing strengths)
  • Combination group: 112 participants
  • Placebo: 156 participants
• Change in log viral load from baseline to day 11
  • 700 mg bamlanivimab: –3.72
  • 2800 mg bamlanivimab: –4.08
  • 7000 mg bamlanivimab: –3.49
  • Combination: –4.37
  • Placebo: –3.80
• Differences in change in log viral load at day 11, compared to placebo
  • 700 mg bamlanivimab: 0.09 (95%,  CI –0.35 to 0.52; P = 0.69)
  • 2800 mg bamlanivimab: –0.27 (95% CI, –0.71 to 0.16; P = 0.21)
  • 7000 mg bamlanivimab: 0.31 (95% CI, –0.13 to 0.760; P = 0.16)
  • Combination: –0.57 (95% CI, –1.00 to –0.14; P = 0.01)
• Proportion of patients with COVID-19-related hospitalizations or ED visits
  • 700 mg bamlanivimab: 1.0% (1 event)
  • 2800 mg bamlanivimab: 1.9% (2 events)
  • 7000 mg bamlanivimab: 2.0% (2 events)
  • Combination: 0.9% (1 event)
  • Placebo: 5.8% (9 events)
• Immediate hypersensitivity reactions were reported in some patients
  • Bamlanivimab: 6 patients
  • Combination: 2 patients
  • Placebo: 1 patient
• No deaths occurred during the study

CONCLUSION:

• For patients with mild to moderate COVID-19, treatment with combined bamlanivimab and etesevimab monoclonal antibodies led to reduction in viral load at day 11, compared to placebo
  • With bamlanivimab therapy only there was no significant reduction in viral load
• An editorial points out that viral load (primary endpoint) can change over the disease course | Hospitalizations (a secondary outcome) may be a more clinically relevant outcome

While the world waits for widespread administration of effective vaccines and additional data on treatments, local efforts should work to improve testing access and turnaround time and reduce logistical barriers to ensure that monoclonal therapies can be provided to patients who are most likely to benefit 

Learn More – Primary Sources:

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

JAMA Editorial: Neutralizing Monoclonal Antibody for Mild to Moderate COVID-19

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