bamlanivimab and etesevimab together

This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.

What were the common treatment emergent adverse events with bamlanivimab and etesevimab treatment?

In the BLAZE-1 trial, most treatment-emergent adverse events were mild to moderate in severity and no deaths were reported with bamlanivimab and etesevimab treatment.

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Bamlanivimab and Etesevimab Emergency Use Authorization

Bamlanivimab and etesevimab have not been approved, but have only been authorized for emergency use by FDA to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization.1,2

Bamlanivimab and etesevimab are authorized to be administered together for the treatment of mild to moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progressing to severe COVID-19 and/or hospitalization only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of the bamlanivimab and etesevimab under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.1,2

For information on the authorized use of bamlanivimab and etesevimab together and mandatory requirements under the EUA, please review the FDA Letter of Authorization, Fact Sheet for Healthcare Providers, and Fact Sheet for Patients/Caregivers at BAMandETE.com.

Bamlanivimab and Etesevimab Fact Sheet for Healthcare Providers

Warnings

There are limited clinical data available for bamlanivimab and etesevimab. Serious and unexpected AEs may occur that have not been previously reported with use of bamlanivimab and etesevimab.2

Patients with known hypersensitivity to any ingredient of bamlanivimab or etesevimab must not receive bamlanivimab or etesevimab.2

Clinical Worsening After Bamlanivimab Administration

Clinical worsening of COVID-19 after administration of bamlanivimab has been reported and may include signs or symptoms of

  • fever
  • hypoxia or increased respiratory difficulty
  • arrhythmia (e.g. atrial fibrillation, sinus tachycardia, bradycardia)
  • fatigue, and
  • altered mental status.2

Some of these events required hospitalization and it is not known if these events were related to bamlanivimab use or were due to progression of COVID-19.2

Side Effects

Adverse events have been reported with bamlanivimab and etesevimab.2

Additional AEs associated with bamlanivimab and etesevimab, some of which may be serious, may become apparent with more widespread use.2

Bamlanivimab and Etesevimab Available Clinical Data

The information presented in the sections below contain data on unauthorized doses of bamlanivimab and etesevimab administered together. The only authorized dose of bamlanivimab and etesevimab administered together for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg) is bamlanivimab 700 mg and etesevimab 1400 mg.

The EUA for bamlanivimab alone has been revoked by the US FDA as of April 16, 2021. Therefore, any information on bamlanivimab alone in the sections below is being provided for scientific and/or educational purposes, and is regarding an unauthorized and unapproved medication and dose. 

Clinical Trial Design Overview

BLAZE-1 is a phase 2/3 randomized, double-blind, placebo-controlled trial evaluating bamlanivimab alone and together with etesevimab, in non-hospitalized patients with mild to moderate COVID-19.3,4BLAZE Clinical Trial Designs summarizes the BLAZE-1 clinical trial designs.

BLAZEa Clinical Trial Designs2-5

 

BLAZE-1 Phase 2 (NCT04427501)

BLAZE-1 Phase 3 (NCT04427501)

Design

Randomized, double-blind, placebo-controlled trial in non-hospitalized patients with mild to moderate COVID-19

Randomized, double-blind, placebo-controlled trial in non-hospitalized patients with mild to moderate COVID-19 and at least 1 risk factorb for developing severe COVID-19 illness

Primary Endpoint

Change from baseline to day 11 in SARS-CoV-2 viral load.

Percentage of participants who experience COVID-related hospitalization or death through Day 29.

Treatment arms included in analyses

Patients randomized to IV infusion of

  • bamlanivimab alone 700mg (n=101), 2800 mg (n=107), or 7000 mg (n=101)
  • bamlanivimab 2800 mg and etesevimab 2800 mg together (n=112), or
  • placebo (n=156)

Patients randomized to IV infusion of

  • bamlanivimab 2800 mg and etesevimab 2800 mg together (n=518), or
  • placebo (n=517)

BAM = bamlanivimab; BMI = body mass index; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; COVID-19 = coronavirus disease 2019; CVD = cardiovascular disease ETE = etesevimab; IV = intravenous; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2.

aBLAZE clinical trials are ongoing studies, outcomes measures, inclusion/exclusion criteria, and eligibility may change throughout the study.

bRisk factors include: ≥ 65 years of age, BMI ≥ 35, CKD, type 1 or type 2 diabetes, immunosuppressive disease, receiving immunosuppressive treatment; ≥ 55 years of age AND have a history of CVD, or hypertension, or COPD or other chronic respiratory disease; 12-17 years of age AND satisfy at least one of the following at the time of screening: BMI ≥85th percentile for their age and gender based on CDC growth charts, sickle cell disease, congenital or acquired heart disease, neurodevelopmental disorders (for example, cerebral palsy), medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation not related to COVID-19), asthma or reactive airway or other chronic respiratory disease, type 1 or type 2 diabetes, immunosuppressive disease, or currently receiving immunosuppressive treatment.

Baseline Demographics and Disease Characteristics

Baseline demographics and disease characteristics were well balanced across treatment groups for each of the studies.2BLAZE Clinical Trials Baseline Demographics and Disease Characteristics provides information by study.

BLAZE Clinical Trials Baseline Demographics and Disease Characteristics2

 

BLAZE-1 Phase 2

BLAZE-1 Phase 3

Median age, years

45

56

≥ 65 years old

12%

31%

Female

55%

52%

White

89%

87%

Hispanic or Latino

43%

29%

Black or African American

6%

8%

High-risk for severe COVID-19 illnessa

42%

100%

Mild COVID-19

78%

77%

Moderate COVID-19

22%

23%

Mean duration of symptoms, days

5 

4

Mean viral load by CT

24

24

Abbreviations: BMI = body mass index; CKD = chronic kidney disease; COVID-19 = coronavirus disease 2019; CT = cycle threshold.

aHigh risk is defined as patients who meet at least one of the following criteria: BMI ≥35, CKD, diabetes, immunosuppressive disease, receiving immunosuppressive treatment, ≥65 years old, ≥55 years old AND have cardiovascular disease, OR hypertension, OR chronic obstructive pulmonary disease/other chronic respiratory disease. Are 12 – 17 years of age AND have BMI ≥85th percentile for their age and gender based, OR sickle cell disease, OR congenital or acquired heart disease, OR neurodevelopmental disorders, OR a medical-related technological dependence, OR asthma, reactive airway or other chronic respiratory disease that requires daily medication for control.

Bamlanivimab and Etesevimab: Overall Summary of Exposure

Approximately 1500 subjects have been exposed to bamlanivimab and etesevimab administered together in clinical trials in ambulatory (non-hospitalized) subjects at doses of bamlanivimab 700 mg and etesevimab 1400 mg or higher.2

More than 3900 subjects have received bamlanivimab (either alone or with etesevimab) at doses ranging from 700 to 7000 mg.2

Bamlanivimab and etesevimab at the authorized doses of 700 mg and 1400 mg have been administered together to approximately 770 subjects.2

Bamlanivimab and Etesevimab: Summary of Safety Results

Treatment-Emergent Adverse Event Classification and Definition

A TEAE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.4,6

TEAE Intensity Classification

The investigator made an assessment of intensity for each TEAE and SAE reported during the study and assigned it to one of the following categories

  • mild: symptoms causing no or minimal interference with usual social and functional activities, with intervention not indicated
  • moderate: symptoms causing greater than minimal interference with usual social and functional activities, with intervention indicated, or
  • severe: symptoms causing inability to perform usual social and functional activities, with intervention or hospitalization indicated.4,6

Serious Adverse Event Definition

A TEAE assessed as severe by the investigator was not necessarily designated as an SAE unless it met the SAE definition.4,6

An SAE is defined as

  • death
  • a life-threatening AE
  • inpatient hospitalization or prolongation of existing hospitalization
  • a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • a congenital anomaly/birth defect, or
  • a medical or surgical intervention to prevent
    • death
    • a life-threatening event
    • hospitalization
    • disability, or
    • congenital anomaly.2,4

BLAZE-1 Phase 2 Safety Data

The safety data presented here are from the interim analysis of the BLAZE-1 phase 2 trial, when the last patient randomized to treatment with bamlanivimab and etesevimab together (2800 mg each; N=112) had reached Day 29 of treatment. .4

In the phase 2 portion of the BLAZE-1 trial,

  • the majority of TEAEs were mild to moderate in severity
  • the frequency of severe TEAEs was similar across treatment groups, and
  • there were no deaths or discontinuations due to AEs.7

Summary of Adverse Events from the BLAZE-1 Phase 2 Study provides a summary of the TEAEs from the interim analysis of the phase 2 BLAZE-1 trial.

Summary of Adverse Events from the BLAZE-1 Phase 2 Study4

n (%)ab

Placebo

(N=156)

BAM 700 mg
Alone 
(N=101)

ETE 2800 mg + BAM 2800 mg
Together
(N=112)

≥1 TEAEs

42 (26.9)

27 (26.7)

19 (17.0)

Mild

21 (13.5)

17 (16.8)

15 (13.4)

Moderate

18 (11.5)

7 (6.9)

3 (2.7)

Severe

3 (1.9)

2 (2.0)

1 (0.9)

SAEs

1 (0.6)

0

1 (0.9)

Death

0

0

0

Abbreviations: % = proportion of patients; BAM = bamlanivimab; COVID-19 = coronavirus disease 2019; ETE = etesevimab; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aIncludes full randomized population that received at least 1 infusion.

bDoes not include SAEs and deaths related to COVID 19, as they are captured as study outcomes.

Treatment -Emergent Adverse Events In BLAZE-1 Phase 2

In the phase 2 portion of the BLAZE-1 trial, there were no clinically meaningful differences between treatment groups in the frequency of TEAEs. The most commonly reported AE across the treatment groups was nausea.2,4

Most Common TEAEs Reported in the BLAZE-1 Phase 2 Study summarizes the common TEAEs occurring in patients in the phase 2 portion of the BLAZE-1 trial.

Most Common TEAEs Reported in the BLAZE-1 Phase 2 Study4

Adverse Events,
n (%)a

Placebo

(N=156)

BAM 700 mg
Alone
(N=101)

BAM 2800 mg + ETE 2800 mg
Together
(N=112)

Chest discomfort

1 (0.6)

0

0

Chills

0

0

0

Diarrhea

7 (4.5)

1 (1.0)

1 (0.9)

Dizziness

3 (1.9)

3 (3.0)

1 (0.9)

Headache

3 (1.9)

3 (3.0)

0

Nasal congestion

1 (0.6)

2 (2.0)

0

Nausea

6 (3.8)

3 (3.0)

4 (3.6)

Pruritus

1 (0.6)

2 (2.0)

2 (1.8)

Pyrexia

0

1 (1.0)

1 (0.9)

Rash

1 (0.6)

1 (1.0)

1 (0.9)

Syncope

2 (1.3)

0

0

Vomiting

4 (2.6)

1 (1.0)

1 (0.9)

Abbreviations: % = proportion of patients; BAM = bamlanivimab; ETE = etesevimab; TEAE = treatment-emergent adverse event.

aIncludes full randomized population that received at least 1 infusion.

BLAZE-1 Phase 3 Safety Data

In the phase 3 portion of the BLAZE-1 trial, AEs occurred in

  • 13% of patients who received a single infusion of bamlanivimab and etesevimab together (2800 mg each; N=518), and
  • 12% of placebo-treated patients (N=517).2

The most common AEs reported were nausea, dizziness, and rash. These events each occurred in 1% of subjects treated with bamlanivimab and etesevimab and in 1% of placebo subjects.2

BLAZE-4: Accelerated Infusion Substudy Results

Safety and Tolerability With 15-Minute Infusion

Summary of Adverse Events With 30-Minute and 15-Minute Bamlanivimab and Etesevimab Infusion summarizes the safety of IV administration of undiluted bamlanivimab (20 mL) and undiluted etesevimab (40 mL) added to an empty infusion bag, and infused to patients over 30 or 15 minutes in the BLAZE-4 substudy.

Summary of Adverse Events With 30-Minute and 15-Minute Bamlanivimab and Etesevimab Infusion7

n (%)a

BAM 700 mg + ETE 1400 mg
30 minutes
(N=6)

BAM 700 mg + ETE 1400 mg
15 minutes
(N=30)

TEAEs

0

3 (10.0)

     Mild

0

2 (6.7)

     Moderate

0

0

     Severe

0

0

     Missing data

0

1 (3.3)

Discontinuation due to AE

0

0

SAEs

0

0

Death

0

0

Abbreviations: % = proportion of patients; AE = adverse event; BAM = bamlanivimab; ETE = etesevimab; SAE = serious adverse event; TEAE = treatment-emergent adverse event.

aNumbers in table represent the number of patients reporting AEs, not number of events.

In the bamlanivimab and etesevimab 15-minute infusion cohort (N = 30), 2 uncoded events were observed. One was defined as an infusion-related reaction and the other defined as shortness of breath/“feeling of infusion” in the chest.7

References

The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).

1United States Food and Drug Administration. Bamlanivimab and Etesevimab FDA Emergency Use Authorization Letter. Issued February 9, 2021. Accessed February 9, 2021. http://pi.lilly.com/eua/bam-and-ete-eua-fda-authorization-letter.pdf

2Fact sheet for healthcare providers. Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. US Food and Drug Administration (FDA). 2021.

3A study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in participants with mild to moderate COVID-19 illness (BLAZE-1). ClinicalTrials.gov identifier: NCT04427501. Updated January 27, 2021. Accessed January 27, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04427501

4Gottlieb RL, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19. JAMA. Published online January 21, 2021. http://dx.doi.org/10.1001/jama.2021.0202

5A study of immune system proteins in participants with mild to moderate COVID-19 illness (BLAZE-4). ClinicalTrials.gov identifier: NCT04634409. Updated January 22, 2021. Accessed January 27, 2021. https://clinicaltrials.gov/ct2/show/NCT04634409

6Chen P, Nirula A, Heller B, et al; BLAZE-1 Investigators. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with covid-19. N Engl J Med. Published online October 28, 2020. https://doi.org/10.1056/nejmoa2029849

7Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

AE = adverse event

COVID-19 = coronavirus disease 2019

EUA = emergency use authorization

FDA = Food and Drug Administration

IV = intravenous

SAE = serious adverse event

SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2

TEAE = treatment-emergent adverse event

Date of Last Review: March 31, 2021


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