Table 3.
Pivotal clinical trials with bamlanivimab/etesevimab, casirivimab/imdevimab and regdanvimab [18,22,84]
| Study | Patients | Treatments | Virologic Outcomes | Clinical Outcomes | Treatment-Emergent AEs | Hypersensitivity/Infusion Reactions | Serious AEs |
|---|---|---|---|---|---|---|---|
| BLAZE-1 [18,70](Phase 2/3) | Ambulatory patients with SARS-CoV-2 infection and ≥1 mild/moderate symptom(s) | Bamlanivimab 700 mg (n = 101) [18] |
Mean difference in change from baseline log viral load versus placebo Day 11: 0.09 log10 cp/mL 95% CI −0.35 to 0.52 |
Hospitalizations or ED visits within 29 days: 1.0% (1 event) |
27 (26.7%) Most common: nausea, diarrhea |
6 events across all bamlanivimab monotherapy doses (1.9%)a | 0 |
| Bamlanivimab 2800 mg (n = 107) [18] |
Mean difference in change from baseline log viral load versus placebo Day 11: −0.27 log10 cp/mL 95% CI −0.71 to 0.16 |
Hospitalizations or ED visits within 29 days: 1.9% (2 events) |
26 (24.3%) Most common: nausea, diarrhea |
0 | |||
| Bamlanivimab 7000 mg (n = 101) [18] |
Mean difference in change from baseline log viral load versus placebo Day 11: 0.31 log10 cp/mL 95% CI −0.13 to 0.76; p = 0.16 |
Hospitalizations or ED visits within 29 days: 2.0% (2 events) |
22 (21.8%) Most common: diarrhea, nausea |
0 | |||
| Bamlanivimab 2800 mg/etesevimab 2800 mg (n = 112) [18] |
Mean difference in change from baseline log viral load versus placebo Day 11: −0.57 log10 cp/mL 95% CI −1.00 to −0.14; p = 0.01 |
Hospitalizations or ED visits within 29 days: 0.9% (1 event) |
19 (17.0%) Most common: nausea, diarrhea |
2 (1.8%)a | 1 (0.9%)b | ||
| Placebo (n = 156) [18] |
Hospitalizations or ED visits within 29 days: 5.8% (9 events) |
42 (26.9%) Most common: diarrhea, nausea |
1 (0.6%)a | 1 (0.6%)c | |||
| Bamlanivimab 2800 mg/etesevimab 2800 mg (n = 518) [70] |
Mean difference in change from baseline log viral load versus placebo Day 7: −1.20 log10 cp/mL 95% CI −1.46 to −0.94; p < 0.001 |
Hospitalizations or death within 29 days: 2.1% (11 patients) |
69 (13.3%) Most common: rash, nausea |
Not reported | 7 (1.4%) | ||
| Placebo (n = 517) [70] |
Hospitalizations or death within 29 days: 7.0% (36 patients) |
60 (11.6%) Most common: rash, nausea, dizziness |
Not reported | 5 (1.0%) | |||
| Weinreich, et al. [22] (Phase 1–2) |
Non-hospitalized patients with SARS-CoV-2 infection | Casirivimab and imdevimab 2.4 g (n = 92) |
LS mean difference in change from baseline log viral load versus placebo Day 7: −0.25 log10 cp/mL 95% CI −0.60 to 0.10 |
Medically attended visit within 29 days: 3% (3 patients) |
Overall incidence not reported Most common AEs of special interest: vomiting, nausea |
0d | 1 (1%) |
| Casirivimab and imdevimab 8.0 g (n = 90) |
LS mean difference in change from baseline log viral load versus placebo Day 7: −0.56 log10 cp/mL 95% CI −0.91 to −0.21 |
Medically attended visit within 29 days: 3% (3 patients) |
Overall incidence not reported Most common AEs of special interest: abdominal pain, pruritus, urticaria, chills, flushing |
2 (2%)d | 0 | ||
| Placebo (n = 93) |
Medically attended visit within 29 days: 6% (6 patients) |
Overall incidence not reported Most common AEs of special interest: hypertension, hypoxia, vomiting, nausea, rash, dizziness, headache |
1 (1%)d | 2 (2%) | |||
| Ison, et al. [84](Phase 2/3 – Part 1) | Non-hospitalized patients with mild-to-moderate SARS-CoV-2 infection | Regdanvimab 40 mg/kg (n = 100) |
Median (95% CI) time to negativef RT-qPCR, days All: 12.8 (9.00–12.87) Mild infection: 12.72 (8.90–12.89) Moderate infection: 12.75 (8.84–15.78) |
Median (95% CI) time to clinical recovery, days: All: 5.4 (3.97–6.78) Mild infection: 4.37 (2.15–7.67) Moderate infection: 5.73 (4.13–7.33) |
31 (29.5%) Most common treatment-emergent AE related to study drug: hypertriglyceridemia |
1 (1.0%) | 0e |
| Regdanvimab 80 mg/kg (n = 103) |
Median (95% CI) time to negativef RT-qPCR, days All: 11.9 (8.94–12.91) Mild infection: 9.05 (8.85–12.92) Moderate infection: 12.72 (8.89–13.82) |
Median (95% CI) time to clinical recovery, days: All: 6.2 (5.53–7.85) Mild infection: 5.49 (3.15–7.60) Moderate infection: 7.30 (5.58–10.72) |
27 (24.5%) No treatment-emergent AE related to study drug reported in >1 patient |
0 | 0e | ||
| Placebo (n = 104) |
Median (95% CI) time to negativef RT-qPCR, days All: 12.9 (12.69–13.89) Mild infection: 12.95 (8.96–15.84) Moderate infection: 12.87 (10.83–15.83) |
Median (95% CI) time to clinical recovery, days: All: 8.8 (6.72–11.73) Mild infection: 6.88 (4.80–8.78) Moderate infection: 10.81 (6.81–n.c.) |
34 (30.9) Most common treatment-emergent AEs related to study drug: hypertriglyceridemia, infusion-related reaction |
2 (1.8%) | 0e | ||
| Ison, et al. [84](Phase 2/3 – Part 2) | Non-hospitalized patients with mild-to-moderate SARS-CoV-2 infection | Regdanvimab 40 mg/kg (n = 656) |
[Exploratory] Mean change from baseline in viral load titer Day 7: –2.770 log10 cp/mL |
Patients progressing to severe COVID-19 up to day 28 (hospitalization, oxygen therapy or mortality): High-risk patients: 3.1% All patients: 2.4% |
198 (30.4%) Specific AEs not reported |
4 (0.6%) | 4 (0.6%)e |
| Placebo (n = 659) |
[Exploratory] Mean change from baseline in viral load titer Day 7: –2.236 log10 cp/mL |
Patients progressing to severe COVID-19 up to day 28 (hospitalization, oxygen therapy or mortality): High-risk patients: 11.1% All patients: 8.0% |
202 (31.1%) Specific AEs not reported |
7 (1.1%) | 1 (0.2%)e |
All trials conducted prior to the current dominance of the omicron variant.
aMost occurred during infusion, were mild in severity and unrelated to dose.
bUrinary tract infection considered unrelated to study medication.
cUpper abdominal pain considered unrelated to study medication.
dGrade ≥2 within 4 days of infusion.
eTreatment-emergent serious AEs.
fThreshold <2.33 log10 cp/mL.
AE: adverse event; CI: confidence interval; COVID-19: coronavirus disease 2019; cp: copies; ED: emergency department; LS: least-squares; n.c.: not calculable; RT-qPCR: quantitative reverse transcription–polymerase chain reaction.