Monoclonal Antibodies Update per CDC/IDSA

Monoclonal antibodies (mAbs) against SARS-CoV-2 spike protein show promise in phase 3 clinical trials for the treatment and prevention of COVID-19

Emergency use authorizations (EUAs) for treatment approved for:

• ambulatory patients 
• with mild to moderate COVID-19 
• at high risk for progression 
• within 10 days of symptoms onset

FDA links: https://www.fda.gov/media/143603/download

https://www.fda.gov/media/143892/dowmload

The mAbs being studied:

• Bamlanivimab (700 mg)
• Casirivimab + Imdevimab (2400mg)

Bamlanivimab (Chen, et al NEJM 2020)

In outpatients with mild to moderate COVID-19, Bamlanivimab appears to:

• accelerate decline in SARs-CoV-2 level compared to placebo
• lower rate of ED visits/hospitalizations (2% vs 6%) in all participants who received Bamlanivimab vs. placebo, particularly among high-risk patients (5% vs. 10%) n=452

Casirivimab + Imdevimab (C/I) (Weinreich et al NEJM 2020)

In outpatients with mild to moderate COVID-19, C/I appears to 

• accelerate decline in SARs-CoV-2 level compared to placebo
• lower rate of ED visits/hospitalizations (2% vs. 4%) in all participants who received C/I vs. placebo, particularly among high-risk patients (3% vs. 9%) n=799

There was 1 anaphylactic reaction and 4 infusion reactions in the 18000 mg group

Timing of C/I administration:

• In a subset of these patients, SARs-CoV-2 endogenous Ab was negative at baseline (n=275, 41%)
• The viral load change was greater in the endogenous Ab negative group than in participants that had already developed endogenous antibodies
• 6% of endogenous antibody negative at baseline and 15% of endogenous antibody positive recipients needed a medically attended visit – suggesting a boost in immune response with therapy.

Bamlanivimab with or without Etesevimab (Gottlieb RL et al, JAMA, 2021) (Phase 2)

• Compared with placebo, differences in change in viral level at day 11 not statistically significant for Bamlanivimab monotherapy
• Significantly greater change in viral level in those who received Bamlanivimab/Etesevimab 

Hospitalizations/ED visit:

• Placebo 5.8%
• Bam 700 mg 1%, 2800 mg 1.9%, 7000 mg 2%
• Bam/Etesevimab 0.9% 

Bamlanivimab with or without Etesevimab Phase 3 (press release)

• N=1035 high risk outpatients within 3 days of a positive SARs-CoV-2 test
• Randomized to receive bam/etesevimab (2800 mg/2800mg) or placebo
• Study population: 65 years or older: 30-32%: mean BMI 33-34
• Duration of symptoms: mean 4.1-4.2 days

1. Hospitalizations/death by any cause at 28 days 2.1% vs 7% (p 0.0004) in Bam/Ete vs. placebo
2. Deaths by day 19 of any cause at day 28  0% vs 1.9%
3. Viral load changes also statistically significant
4. Serious adverse effects: 1.4% vs 1% 

Bamlanivimab in Hospitalized Patients (NEJM 2020)

Hospitalized patients with COVID-19 and without end-organ failure randomized to receive bam vs placebo study stopped for futility after 314 participants enrolled  no evidence for antibody efficacy

Casirivimab/Imdevimab in Hospitalized patients

is still being evaluated in RECOVERY trial and in ongoing trials in patients on low flow oxygen 

Monoclonal Antibodies for Prevention

mAbs offer immediate protection for those exposed or unvaccinated in high-risk settings

• can be provided to patients unlikely to respond to vaccine or allergic
• they could stop viral replication and block progression of disease

Target populations: 

• Nursing home residents and attendants
• High incident workplaces
• Index case contacts (household contacts)

Bamlanivimab for Prevention (BLAZE-2)

Phase 3 trail – Bamlanivimab 4200 mg vs. placebo

Staff and residents in long term care facility with at least one confirmed case of SARs-CoV-2 <=7 days prior to randomization

• Prevention: 965 participants who tested negative for SARs-CoV-2 (299 residents and 666 staff)
• Treatment: 132 participants who tested positive for SARs-CoV-2 (41 residents and 91 staff) and had risk factors for severe SARs-CoV-2 

• Among all participants, lower frequency of symptomatic COVID-19 with Bamlanivimab (OR 0.43 p 0.00021)
• For nursing home residents, lower frequency of symptomatic COVID-19 with Bamlanivimab (OR 0.2, p 0.00026)
• 4 deaths, all in placebo group

Casirivimab/Imdevimab for Prevention 

Ongoing phase 3 trail in household contacts (n=3k)

Exploratory analysis of 400 participants with striking results

Participants were randomized to C/I 1200 mg, subQ, 4 injections or placebo

• Symptomatic +asymptomatic infection: 23/223 placebo, 10/186 in mAb (approx. 50% reduction)
• Decreased in peak viral levels placebo group >100 fold higher peak viral load
• Decreased duration of viral shedding 
• One death, 1 hospitalization in placebo group and none in mAb group

Information current as of 1/30/2021