Monoclonal antibody for COVID-19: Unveiling the recipe of a new cocktail

Table 1 Properties of different studies of antibodies therapy in coronavirus disease 2019

Ref.	Study type	Dose and duration	Primary outcome	Secondary outcomes	Primary result	Additional characteristics	Adverse effects
Chen et al[17], BLAZE-1	Randomised, double-blind, placebo-controlled, single-dose trial	Total 452 patients; 309 in the bamlanivimab (LY-CoV555) group and 143 in the placebo group. mAb at doses of 700 mg, 2800 mg, and 7000 mg and placebo administered within 3 d after positive SARS-CoV-2 results	The change from baseline to day 11 (4 d) in SARS-CoV-2 viral load	COVID-19 related inpatient hospitalisation, a visit to the emergency department, death, safety, symptom severity, and time points for viral clearance	The viral load at day 11 was lower in patients who received 2800 mg drug compared to the placebo group	High-risk subgroups (an age of ≥ 65 yr or a BMI of ≥ 35), the percentage of hospitalisation was 4.2% in the LY-CoV555 group and 14.6% in the placebo group	Serious adverse events occurred in none of the patient treatment groups, diarrhoea was reported in 3.2% of the patients
Weinreich et al[23], REGN-COV2	Double-blind, phase 1-3 trial, 275 (1:1:1) non-hospitalised patients with COVID-19	REGN-COV2 is a combination of casirivimab (REGN10933) and imdevimab (REGN10987). Among the 275 patients, 90 were assigned to receive high-dose (8.0 g), 92 to receive low-dose (2.4 g), and 93 to receive placebo	The time-weighted average change in viral load from baseline (day 1) through day 7	The percentage of patients with at least one COVID-19 related medically attended visit through day 29	REGN-COV2 enhanced clearance of virus, particularly in patients in whom an endogenous immune response had not yet been initiated	The median age was 44.0 yr, 49% were male, 13% identified as Black or African American, and 56% as Hispanic or Latino	In this interim analysis, both REGN-COV2 doses (2.4 g and 8.0 g) were associated with few and low-grade toxic effects (1%) in the combined REGN-COV2 dose groups
Gottlieb et al[20], BLAZE 1	Multipart, 49 United States centres including phase 2/3, randomised, double-blind, placebo-controlled, single-infusion study (BLAZE-1) ambulatory patients (n = 613) and had one or more mild to moderate symptom	Patients were randomised to receive a single infusion of bamlanivimab [700 mg (n = 101), 2800 mg (n = 107), or 7000 mg (n = 101)], the combination treatment (2800 mg of bamlanivimab and 2800 mg of etesevimab (n = 112), or placebo (n = 156)	Change in SARS-CoV-2 log viral load at day 11 (± 4 d)	A total of nine prespecified secondary outcome measures were evaluated. Three focused on viral load (time to viral clearance; the proportion of patients with viral support at days 7, 11, 15, and 22; time to symptom improvement; time to symptom resolution; and the balance of patients showing symptom improvement or resolution at days 7, 11, 15, and 22), and 1 focused on clinical outcomes (the proportion of patients with a COVID-19 related hospitalisation, emergency department visit, or death) at day 29	Among the 577 patients who were randomised and received an infusion, 533 (92.4%) completed the efficacy evaluation period (day 29). The change in log viral load from baseline at day 11 was –3.72 for 700 mg, –4.08 for 2800 mg, –3.49 for 7000 mg, –4.37 for combination treatment, and –3.80 for placebo	The mean age of patients was 44.7 ± 15.7 yr. A total of 315 patients (54.6%) were female, 245 patients (42.5%) identified as Hispanic, and 387 patients (67.1%) had at least one risk factor for severe COVID-19 (aged ≥ 55 yr, BMI ≥ 30, or ≥ 1 relevant comorbidity such as hypertension)	Immediate hypersensitivity reactions were reported in 9 patients (6 bamlanivimab, 2 combination treatment, and 1 placebo). No deaths occurred during the study treatment
BLAZE-2[21]	Randomised, double-blind, single-dose, phase 3 placebo-controlled trial, 966 participants (300 residents and 666 staff) who tested negative for SARS-CoV-2 at baseline	Bamlanivimab 4200 mg or placebo only if a nursing home recorded at least one confirmed case of SARS-CoV-2 infection among residents or facility staff from a sample collected within the last 7 d	To find incidence of COVID-19, defined as the detection of SARS-CoV-2 by reverse transcriptase-PCR and mild or worse disease severity within 21 d of detection, within 8 wk of randomisation	To find incidence of moderate or worse COVID-19 severity and incidence of SARS-CoV-2 infection	Bamlanivimab significantly reduced the incidence of COVID-19 in the prevention population compared with placebo [8.5% vs 15.2%; odds ratio: 0.43 (95%CI: 0.28-0.68); P < 0.001]; absolute risk difference, −6.6 (95%CI: −10.7 to −2.6 percentage points)	Significantly reduced the incidence of moderate or worse COVID-19 compared with placebo (8.3% vs 14.1%)	The rate of participants with adverse events was 20.1% in the bamlanivimab group and 18.9% in the placebo group. The most common adverse events were urinary tract infection (2.0%) in bamlanivimab and (2.4%) placebo and hypertension (1.2%) in bamlanivimab and (1.7%) placebo
Lundgren et al[18], ACTIVE-3	Randomised, double-blind, placebo-controlled trial	Hospitalised COVID-19 patients (n = 314) without end organ failure, single infusion of the neutralising mAb antibody LY-CoV555 (at a dose of 7000 mg)	A sustained recovery, as assessed in a time-to-event analysis, through day 90 as well as two ordinal outcomes that were measured at day 5	Death from any cause	Hospitalised patients with COVID-19 who received mAb did not have better clinical outcomes at day 5 than those who received placebo	The majority of patients had hypoxemia and tested the effect of LY-CoV555 on a background of remdesivir and substantial glucocorticoid therapy	Serious adverse events (19%) in the LY-CoV555 group and (14%) in the placebo
REGN-COV206724	Phase (I-III) adaptive randomised placebo control double-blind	COVID-19 in infected non-hospitalised patients (n = 4567; REGN-COV2067)	1200 mg cocktail (n = 736), placebo (n = 748), and another group cocktail dose 2400 mg IV (n = 1355), placebo (n = 1341)	Clinically significant effect on risk of COVID-19 hospitalisation or all-cause death in high-risk non-hospitalised patients and confirm safety	Cocktail of casirivimab and imdevimab significantly reduced the risk of hospitalisation or death by 70% (1200 mg IV) and 71% (2400 mg IV) compared to placebo	Cocktail therapy reduced symptom duration from 14 d to 10 d (median numbers)	Not mentioned

BMI: Body mass index; COVID-19: Coronavirus disease 2019; IV: intravenous; mAb: Monoclonal antibody; SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2.