Bamlanivimab–Etesevimab for Mild to Moderate COVID-19 in Patients at High Risk of Progression
- The phase 3 portion of the BLAZE-1 trial examined the efficacy of bamlanivimab plus etesevimab in preventing the progression of early mild or moderate COVID-19 in 1,035 adolescent and adult patients with certain preexisting medical conditions
- By day 29 after a single infusion, the incidence of COVID-19–related hospitalization or death from any cause was 4.8 percentage points lower among patients who received bamlanivimab plus etesevimab than among those who received placebo—a 70% relative reduction in risk
- No deaths or hospitalizations were reported among the patients who received bamlanivimab plus etesevimab, whereas 10 deaths occurred in the placebo group (nine deaths were considered COVID-19–related)
- The incidence of serious adverse events was low and similar in the bamlanivimab–etesevimab group (1.4%) and the placebo group (1.0%), indicating that bamlanivimab plus etesevimab has an acceptable safety profile for high-risk populations
In February 2021, the FDA issued an Emergency Use Authorization (EUA) that permits the use of the unapproved monoclonal antibodies bamlanivimab and etesevimab, administered together, for the treatment of mild to moderate COVID-19 in adults and pediatric patients (age ≥12 years and weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death.
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Michael Dougan, MD, PhD, physician in the Division of Gastroenterology and director of the GI Center for Cancer Complications at Massachusetts General Hospital and the Mass General Cancer Center, served as one of the BLAZE-1 Investigators, who conducted the clinical trial that supported the EUA. He is the first author of the published trial outcomes report in The New England Journal of Medicine.
Recruitment for the phase 3 portion of BLAZE-1 lasted from September 4 to December 8, 2020. The database was locked on January 20, 2021. The investigators included 1,035 adolescent and adult outpatients who had been diagnosed recently with mild or moderate COVID-19 and had at least one risk factor for severe COVID-19 as specified below. 29% of patients identified as Hispanic or Latinx and 8% identified as Black.
In a randomized, double-blind fashion, the patients were assigned to receive a single one-hour intravenous infusion of either placebo or the combination of 2800 mg bamlanivimab and 2800 mg etesevimab (BE). The median time between symptom onset and treatment was four days.
Risk Factor Inclusion Criteria
Adolescents 12–17 years old:
- BMI ≥85th percentile for age and sex
- Sickle cell disease
- Congenital or acquired heart disease
- Neurodevelopmental disorder such as cerebral palsy
- Dependence on a medical-related mechanical device or procedure such as tracheostomy, gastrostomy or positive-pressure ventilation (unrelated to COVID-19)
- Chronic respiratory disease
- Type 1 or type 2 diabetes
- Immunocompromised condition or receipt of immunosuppressive treatment
Adults ≥65 years old:
- BMI ≥35
- Chronic kidney disease
- Diabetes mellitus type 1 or 2
- Immunosuppressive disease or receipt of immunosuppressive treatment
- Age ≥55 with cardiovascular disease, hypertension or chronic respiratory disease
The primary outcome was the composite of COVID-19–related hospitalization or death from any cause by day 29:
- BE group: 2.1%
- Placebo group: 7.0%
The absolute risk difference was −4.8 percentage points (relative risk difference, 70%; P<0.001).
Other Efficacy Measures
- Death by day 29: 0 in the BE group vs. 10 in the placebo group (9 were judged COVID-19–related by trial staff unaware of group assignment)
- COVID-19–related hospitalization, emergency department visit or death from any cause by day 29: 2.3% vs. 7.2% (P<0.001)
- Time to sustained resolution of symptoms: 8 days vs. 9 days (P=0.007)
Adverse events (AEs) were reported in 13.3% of the BE group and 11.6% of the placebo group. Serious AEs occurred in 1.4% and 1.0%, respectively. In both groups, the most common AEs were nausea, rash, dizziness, diarrhea and hypertension. No deaths were reported among the patients who received bamlanivimab plus etesevimab.
Based on results from BLAZE-2, a separate trial, the FDA revised the EUA in September 2021 to authorize the use of bamlanivimab plus etesevimab as post-exposure prophylaxis for prevention of COVID-19 in people who have been exposed to SARS-CoV-2 and are not fully vaccinated or are not expected to have sufficient immune response to vaccination.
Both trials were funded by Eli Lilly.
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