Table 3a. Anti-SARS-CoV-2 Monoclonal Antibodies: Selected Clinical Data

Last Updated: April 21, 2021

Table 3a. Anti-SARS-CoV-2 Monoclonal Antibodies: Selected Clinical Data
Study Design Methods Results Limitations and Interpretation
Bamlanivimab Plus Etesevimab Versus Placebo in Outpatients With COVID-19 (BLAZE-1)1,2

Double-blind, Phase 3 RCT in outpatients with mild to moderate COVID-19 who are at high risk for progressing to severe COVID-19 and/or hospitalization as defined in the BAM plus ETE EUA (n = 1,035)

Note: These data are from the FDA EUA for BAM plus ETE and from a conference abstract presentation.

Key Inclusion Criteria:
  • Aged ≥12 years
  • Not currently hospitalized
  • ≥1 mild or moderate COVID-19 symptom
  • At high risk for progressing to severe COVID-19 and/or hospitalization

Key Exclusion Criteria:

  • SpO2 ≤93% on room air, or
  • Respiratory rate ≥30 breaths/min, or
  • Heart rate ≥125 bpm

Interventions:

  • Single IV infusion of:
    • BAM 2,800 mg plus ETE 2,800 mg, or
    • Placebo
  • Administered within 3 days after receiving a positive result on a SARS-CoV-2 virologic test

Primary Endpoint:

  • Proportion of participants with COVID-19 related hospitalization (defined as ≥24 hours of acute care) or death by any cause by Day 29

Secondary Endpoints:

  • Proportion of participants with persistently high VL (defined as SARS-CoV-2 level >5.27 log10 copies/mL) at Day 7
  • Mean change in VL from baseline to Days 3, 5, and 7
Number of Participants:
  • BAM plus ETE (n = 518) and placebo (n = 517)

Participant Characteristics:

  • Median age was 56 years; 31% of the participants were aged ≥65 years.
  • 48% of the participants were men.
  • 87% of the participants were White; 8% were Black or African American; and 29% were Hispanic/Latinx.
  • Mean duration of symptoms was 4 days.
  • 77% of the participants had mild COVID-19.

Primary Outcomes:

  • Proportion of participants with COVID-19 related hospitalization or death by any cause by Day 29:
    • 11 of 518 participants (2.1%) in the BAM plus ETE arm vs. 36 of 517 (7.0%) in the placebo arm (P = 0.0004)
    • Relative reduction: 70%
  • Proportion of participants who had died from any cause by Day 29:
    • 0 of 518 participants (0%) in the BAM plus ETE arm vs. 10 of 517 (1.9%) in the placebo arm (P < 0.001).

Secondary Outcomes:

    The proportion of participants with persistently high VLs at Day 7 was 10% in the BAM plus ETE arm vs. 29% in the placebo arm (P < 0.000001).
Limitations:
  • Trial data have not yet been peer reviewed and published.

Interpretation:

  • There was a 5% absolute reduction and a 70% relative reduction in COVID-19-related hospitalizations or deaths from any cause among the participants who received BAM plus ETE compared to those who received placebo.
  • Data are for a BAM plus ETE dose which is not the dose authorized in the EUA.
REGN10933 and REGN10987 (Casirivimab Plus Imdevimab) Versus Placebo in Outpatients with COVID-19 (Modified Full Analysis of R10933-10987-COV-2067 Trial)3

Double-blind, Phase 3 RCT in outpatients with mild to moderate COVID-19 (n = 4,180 for modified full analysis subset of the Phase 3 trial)

These data are publicly available but have not been peer reviewed or published.

Key Inclusion Criteria:
  • Onset of COVID-19 symptoms ≤7 days before randomization
  • SARS-CoV-2 PCR positive at baseline
  • Criteria only for the modified full analysis:
    • Aged ≥18 years
    • ≥1 risk factor for severe COVID-19

Interventions:

  • Single IV infusion of:
  • CAS 600 mg plus IMD 600 mg,
  • CAS 1,200 mg plus IMD 1,200 mg, or
  • Placebo

Endpoint:

  • Proportion of participants with COVID-19-related hospitalization or all-cause death through Day 29
Number of Participants:
  • CAS 600 mg plus IMD 600 mg (n = 736) vs. placebo (n = 748)
  • CAS 1,200 mg plus IMD 1,200 mg (n = 1,355) vs. placebo (n = 1,341)

Participant Characteristics:

  • Median age was 50 years.
  • 35% of the participants were Hispanic/Latinx and 5% were Black or African American.
  • Median duration of symptoms prior to enrollment was 3 days (IQR 2–5 days).4

Outcomes:

  • Percentage of participants with COVID-19-related hospitalization or all-cause death through Day 29 (based on participants in the modified cohort):
    • 7 of 736 (1.0%) in the CAS 600 mg plus IMD 600 mg arm vs. 24 of 748 (3.2%) in the placebo arm (P = 0.0024)
    • 18 of 1,355 (1.3%) in the CAS 1,200 mg plus IMD 1,200 mg arm vs. 62 of 1,341 (4.6%) in the placebo arm (P < 0.0001)
  • Percentage of participants who died (based on all study participants):
    • 1 of 827 (0.1%) in the CAS 600 mg plus IMD 600 mg arm
    • 1 of 1,849 (0.05%) in the CAS 1,200 mg plus IMD 1,200 mg arm
    • 5 of 1,843 (0.3%) in the placebo arm
Limitations:
  • The modified full analysis data have not been peer reviewed or published.
  • Details of the study design, follow-up, and full methods are limited.

Interpretation:

  • There was a 2.2% absolute reduction and a 70% relative risk reduction in COVID-19-related hospitalizations or all-cause deaths in participants who received CAS 600 mg plus IMD 600 mg compared to those who received placebo.
  • There was a 3.3% absolute reduction and a 71% relative risk reduction in COVID-19 related hospitalizations and all-cause deaths in participants who received CAS 1,200 mg plus IMD 1,200 mg compared to those who received placebo.
REGN10933 and REGN10987 (Casirivimab Plus Imdevimab) Versus Placebo in Outpatients With COVID-19 (R10933-10987-COV-2067 Trial)5

Double-blind, Phase 1 and 2 RCT in outpatients with mild to moderate COVID-19 (n = 799)

Note: These data are from the FDA EUA for CAS plus IMD.

Key Inclusion Criteria:
  • Onset of COVID-19 symptoms ≤7 days before randomization
  • SpO2 ≥93% on room air

Key Exclusion Criteria:

  • Hospitalization before or at randomization due to COVID-19
  • Prior, current, or planned future use of any of the treatments specified in the protocol (e.g., COVID-19 CP, IVIG for any indication)

Interventions:

  • Single IV infusion of:
    • CAS plus IMD 2,400 mg (CAS 1,200 mg and IMD 1,200 mg),
    • CAS plus IMD 8,000 mg (CAS 4,000 mg and IMD 4,000 mg), or
    • Placebo
  • Administered ≤3 days after receiving a positive result on a SARS-CoV-2 virologic test

Primary Endpoint:

  • TWA change in NP VL from baseline to Day 7

Secondary Endpoints:

  • COVID-19-related medical visits including hospitalization or ED, urgent care, or physician office/telemedicine visit within 28 days of treatment
  • Safety
  • Symptom improvement
Number of Participants:
  • CAS plus IMD (n = 533):
    • CAS plus IMD 2,400 mg (n = 266)
    • CAS plus IMD 8,000 mg (n = 267)
  • Placebo (n = 266)

Participant Characteristics:

  • Median age was 42 years; 7% of the participants were aged ≥65 years.
  • 34% of the participants had risk factors for severe COVID-19.
  • Median duration of symptoms was 3 days.

Primary Outcomes:

  • The primary endpoint was evaluated in the modified full analysis set of participants with detectable virus at baseline (n = 665).
  • TWA change in NP VL at Day 7 was greater among the CAS plus IMD-treated participants overall than among the placebo-treated participants (-0.36 log10 copies/mL; P < 0.0001).

Secondary Outcomes:

  • The proportion of participants who had COVID-19-related medical visits within 28 days of treatment was lower in the combined CAS plus IMD arms than in the placebo arm:
    • Combined CAS plus IMD arms: 2.8% of patients
    • Placebo arm: 6.5% of patients
  • In a post hoc analysis, percentage of participants who were hospitalized or had a medical visit within 28 days of treatment:
    • All CAS plus IMD doses: 8 of 434 (2%)
    • CAS plus IMD 2,400 mg: 4 of 215 (2%)
    • CAS plus IMD 8,000 mg: 4 of 219 (2%)
    • Placebo: 10 of 231 (4%)
  • In a post hoc analysis, percentage of participants at high-risk for progression to severe COVID-19 and/or hospitalization who required hospitalization or ED visit:
    • All CAS plus IMD doses: 4 of 151 (3%)
    • Placebo: 7 of 78 (9%)
  • Median time to symptom improvement:
    • Combined CAS plus IMD arms: 5 days
    • Placebo arm: 6 days
  • The safety profile of CAS plus IMD was similar to the profile for the placebo.
  • 4 infusion related reactions of grade 2 severity or higher were reported in the CAS plus IMD 8,000 mg arm resulting in permanent discontinuation of the infusion in 2 participants; 1 participant had an anaphylactic reaction that resolved with treatment.
Limitations:
  • Relatively small number of participants in each arm
  • Low number of hospitalizations or ED visits

Interpretation:

  • Compared to placebo, a single infusion of CAS plus IMD showed a reduction in NP VL at Day 7 among outpatients with mild or moderate COVID-19.
  • The combined hospitalization or ED visit rate was lower in the CAS plus IMD arms than in the placebo arm, but the number of events in each arm was small.
  • Because of the small number of clinical events, it is difficult to draw definitive conclusions about the clinical benefit of CAS plus IMD from this study. Additional data from a follow-up trial have been reported but remain unpublished.

REGN10933 (Casirivimab) Plus REGN10987 (Imdevimab) Versus Placebo in Outpatients With COVID-19 (R10933-10987-COV-2067 Interim Analysis)6

Note: The data presented in this published interim analysis represent a subset of participants described in the CAS plus IMD EUA (see study above).

Double-blind, Phase 1 and 2 RCT in outpatients with mild to moderate COVID-19 (n = 275) Key Inclusion Criteria:
  • Onset of COVID-19 symptoms ≤7 days before randomization
  • SpO2 ≥93% on room air

Key Exclusion Criteria:

  • Hospitalization before or at randomization due to COVID-19
  • Prior, current, or planned future use of any of the treatments specified in the protocol (e.g., COVID-19 CP, IVIG for any indication)

Interventions:

  • Single IV infusion of:
    • CAS plus IMD 2,400 mg (CAS 1,200 mg and IMD 1,200 mg),
    • CAS plus IMD 8,000 mg (CAS 4,000 mg and IMD 4,000 mg), or
    • Placebo
  • Administered ≤3 days after receiving a positive result on a SARS-CoV-2 virologic test

Primary Endpoint:

  • TWA change in NP VL from baseline to Day 7 in participants with negative serum antibody status at baseline

Secondary Endpoints:

  • COVID-19-related medical visits, including hospitalization or ED, urgent care, or physician office/telemedicine visit within 28 days of treatment
  • Safety
  • Symptom improvement
Number of Participants:
  • All CAS plus IMD doses (n = 182):
    • CAS plus IMD 2,400 mg (n = 92)
    • CAS plus IMD 8,000 mg (n = 90)
  • Placebo (n = 93)

Participant Characteristics:

  • Median age was 44 years (range 35–52 years).
  • Median time from symptom onset to randomization was 3 days.
  • Baseline serum antibody status:
    • Positive: 45% of participants
    • Negative: 41% of participants
    • Unknown: 14% of participants

Primary Outcomes:

  • Primary endpoint evaluated in modified full analysis set of participants with detectable virus at baseline (n = 221).
  • TWA change in NP VL at Day 7 was greater among the participants who received CAS plus IMD (-1.74 ± 0.11 log10 copies/mL; 95% CI, -1.95 to -1.53) than among those who received placebo (-1.34 ± 0.13 log10 copies/mL; 95% CI, -1.60 to -1.08).
  • Among the participants with a negative serum antibody status at baseline, TWA change in VL was greater among those who received CAS plus IMD (-1.94 ± 0.13 log10 copies/mL; 95% CI, -2.20 to -1.67) than among those who received placebo (-1.37 ± 0.20 log10 copies/mL; 95% CI, -1.76 to -0.98).

Secondary Outcomes:

  • The percentage of participants who had COVID-19-related medical visits within 28 days of treatment was lower in the CAS plus IMD arms than in the placebo arm:
    • All CAS plus IMD doses: 6 of 182 (3%)
    • Placebo: 6 of 93 (6%)
  • Among participants with negative serum antibody status at baseline, the percentage of those who had COVID-19-related medical visits within 28 days of treatment was lower in the CAS plus IMD arms:
    • All CAS plus IMD doses: 5 of 80 (6%)
    • Placebo: 5 of 33 (15%)
  • The safety profile of CAS plus IMD was similar to the profile of the placebo; 2 hypersensitivity or infusion related reactions of grade 2 severity or higher were reported in both the CAS plus IMD 8,000 mg arm and the placebo arm.
  • The mean half-life for both CAS and IMD antibodies ranged from 25–37 days.
Limitations:
  • No formal hypothesis testing
  • Interim analysis
  • Relatively small number of participants in each arm
  • These data represent only a subset of participants described in the CAS plus IMD EUA (see the study above).
  • Low number of medical visits

Interpretation:

  • Compared to placebo, a single infusion of CAS plus IMD showed a reduction in VL at Day 7 among outpatients with mild or moderate COVID-19.
  • The percentage of participants with medical visits was lower in the CAS plus IMD arms than in the placebo arm, but the number of events in each arm was small.
  • CAS plus IMD may have a greater effect in patients who are serum antibody negative but further investigation is needed.
  • Because of the small number of clinical events, it is difficult to draw definitive conclusions about the clinical benefit of CAS plus IMD from this study.