Table 4b. Anti-SARS-CoV-2 Monoclonal Antibodies: Selected Clinical Data

Last Updated: April 29, 2022

This table describes only the clinical trials that have evaluated anti-SARS-CoV-2 mAbs for the treatment of COVID-19. Please see Prevention of SARS-CoV-2 Infection for a discussion of the clinical trials that have evaluated anti-SARS-CoV-2 mAbs for PEP of SARS-CoV-2 infection.

Table 4b. Anti-SARS-CoV-2 Monoclonal Antibodies: Selected Clinical Data
Methods	Results	Limitations and Interpretation
BLAZE-1: Double-Blind RCT of Bamlanivimab 700 mg Plus Etesevimab 1,400 mg in Nonhospitalized Patients With Mild to Moderate COVID-19 in the United States and Puerto Rico¹
Key Inclusion Criteria Aged ≥12 years At high risk for severe COVID-19 or hospitalization Interventions Within 3 days of a positive SARS-CoV-2 test result, single infusion of: BAM 700 mg plus ETE 1,400 mg (n = 511) Placebo (n = 258) Primary Endpoint COVID-19-related hospitalization (defined as ≥24 hours of acute care) or death from any cause by Day 29	Participant Characteristics Median age 56 years; 30% aged ≥65 years; 53% women 87% White, 27% Hispanic/Latinx, 8% Black/African American Mean duration of symptoms was 4 days 76% with mild COVID-19, 24% with moderate COVID-19 Primary Outcomes COVID-19-related hospitalizations or all-cause deaths by Day 29: 4 (0.8%) in BAM plus ETE arm vs. 15 (5.8%) in placebo arm (change of -5.0%; 95% CI, -8.0% to -2.1%; P < 0.001) All-cause deaths by Day 29: 0 in BAM plus ETE arm vs. 4 (1.6%) in placebo arm	Key Limitation Conducted before widespread circulation of the Omicron VOC Interpretation Compared to placebo, BAM plus ETE significantly reduced the number of COVID-19-related hospitalizations and all-cause deaths in high-risk patients.
BLAZE-4, Treatment Arms 9–11: Double-Blind RCT of Bamlanivimab Plus Etesevimab Plus Bebtelovimab Versus Bebtelovimab Alone Versus Placebo in Low-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19²
Key Inclusion Criteria Aged 18–64 years No risk factors for progression to severe COVID-19 Key Exclusion Criteria ≥1 of the following: SpO₂ ≤93% on room air Respiratory rate ≥30 breaths/min Heart rate ≥125 bpm Interventions Within 3 days of a positive SARS-CoV-2 test result, single infusion of: BAM 700 mg plus ETE 1,400 mg plus BEB 175 mg (n = 127) BEB 175 mg (n = 125) Placebo (n = 128) Primary Endpoint Proportion of patients with PHVL (defined as SARS-CoV-2 VL >5.82 log₁₀ by Day 7) Key Secondary Endpoints Mean change in VL from baseline to Days 3, 5, 7, and 11 COVID-19-related hospitalization or death from any cause by Day 29 Time to sustained symptom resolution	Participant Characteristics Median age 35 years; 56% women 36% Hispanic/Latinx, 19% Black/African American Mean duration of symptoms prior to enrollment was 3.6 days Primary Outcomes Proportion with PHVL: 13% in BAM plus ETE plus BEB arm vs. 21% in placebo arm (P = 0.098), with a relative reduction of 38% (95% CI, -9% to 65%) 14% in BEB arm vs. 21% in placebo arm (P = 0.147), with a relative reduction of 34% (95% CI, -15% to 62%) Secondary Outcomes Mean decline in VL greater in mAb arms vs. placebo arm at Day 5 but not at Days 3, 7, or 11 COVID-19-related hospitalizations or all-cause deaths by Day 29: 3 (2.4%) in BAM plus ETE plus BEB arm, including 1 death 2 (1.6%) in BEB arm 2 (1.6%) in placebo arm Median time to sustained symptom resolution: 7 days in BAM plus ETE plus BEB arm vs. 8 days in placebo arm (P = 0.289) 6 days in BEB arm vs. 8 days in placebo arm (P = 0.003)	Key Limitations Only low-risk patients included Not powered to assess hospitalizations and deaths Conducted before widespread circulation of the Omicron VOC Interpretations There were no differences in the proportion of patients with PHVL across the arms. Few COVID-19-related hospitalizations or deaths from any cause occurred by Day 29 across the arms, as is expected for a population of individuals who were at low risk of severe COVID-19. Compared to placebo, the median time to sustained symptom resolution was shorter in the BEB arm.
BLAZE-4, Treatment Arms 12 and 13: Open-Label RCT of Bamlanivimab Plus Etesevimab Plus Bebtelovimab and Bebtelovimab Alone in High-Risk, Nonhospitalized Patients With Mild to Moderate COVID-19²
Key Inclusion Criteria Aged ≥12 years Weight ≥40 kg ≥1 risk factor for progression to severe COVID-19 Key Exclusion Criteria ≥1 of the following: SpO₂ ≤93% on room air Respiratory rate ≥30 breaths/min Heart rate ≥125 bpm Interventions Within 3 days of a positive SARS-CoV-2 test result, single infusion of: BAM 700 mg plus ETE 1,400 mg plus BEB 175 mg (n = 50) BEB 175 mg (n = 100) Efficacy Endpoints COVID-19-related hospitalization or death from any cause by Day 29 Mean change in VL from baseline to Days 3, 5, 7, and 11	Participant Characteristics Median age 50 years; 52% women 18% Hispanic/Latinx, 18% Black/African American Mean duration of symptoms prior to enrollment was 4.7 days 21% had at least 1 dose of COVID-19 vaccine Efficacy Outcomes COVID-19-related hospitalization or death from any cause by Day 29: 2 (4%) in BAM plus ETE plus BEB arm vs. 3 (3%) in BEB arm Mean decline in VL greater in BAM plus ETE plus BEB arm vs. BEB arm at Day 5 but not at Days 3, 7, or 11	Key Limitations Open-label study No placebo arm Not powered to assess hospitalizations and deaths Conducted before widespread circulation of the Omicron VOC Interpretation There was no difference in the proportion of patients who were hospitalized or who died between the arms.
Double-Blind RCT of Casirivimab Plus Imdevimab in Nonhospitalized Patients With Mild to Moderate COVID-19³
Key Inclusion Criteria Aged ≥18 years Laboratory-confirmed SARS-CoV-2 infection Symptom onset within 7 days of randomization For patients included in the modified full analysis only: ≥1 risk factor for severe COVID-19 Positive SARS-CoV-2 RT-PCR result at baseline Interventions Single IV infusion of: CAS 600 mg plus IMD 600 mg (n = 736) or placebo (n = 748) CAS 1,200 mg plus IMD 1,200 mg (n = 1,355) or placebo (n = 1,341) Primary Endpoint ≥1 COVID-19-related hospitalization or death from any cause by Day 29	Participant Characteristics Median age 50 years 35% Hispanic/Latinx, 5% Black/African American Median duration of symptoms prior to enrollment was 3 days Primary Outcomes COVID-19-related hospitalizations or all-cause deaths through Day 29: 7 (1.0%) in CAS 600 mg plus IMD 600 mg arm vs. 24 (3.2%) in placebo arm (P = 0.002) 18 (1.3%) in CAS 1,200 mg plus IMD 1,200 mg arm vs. 62 (4.6%) in placebo arm (P < 0.001) All-cause deaths: 1 (0.1%) in CAS 600 mg plus IMD 600 mg arm vs. 1 (0.1%) in placebo arm 1 (< 0.1%) in CAS 1,200 mg plus IMD 1,200 mg arm vs. 3 (0.2%) in placebo arm	Key Limitation Conducted before widespread circulation of the Omicron VOC Interpretation Compared to placebo, CAS 600 mg plus IMD 600 mg and CAS 1,200 mg plus IMD 1,200 mg reduced the risk of COVID-19-related hospitalizations or all-cause deaths in patients with mild to moderate COVID-19.
COMET-ICE: Double-Blind RCT of Sotrovimab in Nonhospitalized Patients With Mild to Moderate COVID-19 in Brazil, Canada, Peru, Spain, and the United States⁴
Key Inclusion Criteria Aged ≥18 years ≥1 comorbidity or aged ≥55 years Positive SARS-CoV-2 RT-PCR or antigen test result Symptom onset ≤5 days before enrollment Key Exclusion Criteria Hospitalized or required supplemental oxygen Severely immunocompromised Interventions SOT 500 mg IV (n = 528) Placebo (n = 529) Primary Endpoint Hospitalization or death from any cause by Day 29	Participant Characteristics Median age 53 years; 20% aged ≥65 years; 54% women 65% Hispanic/Latinx, 8% Black/African American 63% with obesity; 22% with DM; 17% with moderate to severe asthma Primary Outcome Hospitalizations or all-cause deaths by Day 29: 6 (1%) in SOT arm vs. 30 (6%) in placebo arm, including 2 deaths (adjusted relative risk 0.21; 95% CI, 0.09–0.50; absolute difference -4.53%; 95% CI, -6.70% to -2.37%; P < 0.001)	Key Limitation Conducted before widespread circulation of the Omicron VOC Interpretation Compared to placebo, SOT reduced the incidence of all-cause hospitalizations and deaths among patients with mild to moderate COVID-19.
Key: BAM = bamlanivimab; bpm = beats per minute; BEB = bebtelovimab; CAS = casirivimab; DM = diabetes mellitus; ETE = etesevimab; IMD = imdevimab; IV = intravenous; mAb = monoclonal antibody; PEP = post-exposure prophylaxis; PHVL = persistently high viral load; RCT = randomized controlled trial; RT-PCR = reverse transcription polymerase chain reaction; SOT = sotrovimab; SpO₂ = oxygen saturation; VL = viral load; VOC = variant of concern

References

Dougan M, Azizad M, Mocherla B, et al. A randomized, placebo-controlled clinical trial of bamlanivimab and etesevimab together in high-risk ambulatory patients with COVID-19 and validation of the prognostic value of persistently high viral load. Clin Infect Dis. 2021;Published online ahead of print. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34718468.
Food and Drug Administration. Fact sheet for healthcare providers: emergency use authorization for bebtelovimab. 2022. Available at: https://www.fda.gov/media/156152/download.
Weinreich DM, Sivapalasingam S, Norton T, et al. REGEN-COV antibody combination and outcomes in outpatients with COVID-19. N Engl J Med. 2021;385(23):e81. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34587383.
Gupta A, Gonzalez-Rojas Y, Juarez E, et al. Effect of sotrovimab on hospitalization or death among high-risk patients with mild to moderate COVID-19: a randomized clinical trial. JAMA. 2022;327(13):1236-1246. Available at: https://www.ncbi.nlm.nih.gov/pubmed/35285853.