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; no deaths were reported in the bamlanivimab/ etesevimab treatment arm.

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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 progression to severe COVID-19, including hospitalization or death.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 progression to severe COVID-19, including hospitalization or death 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 www.LillyAntibody.com.

Bamlanivimab and etesevimab are not authorized for use in states, territories, and US jurisdictions in which the combined frequency of variants resistant to bamlanivimab and etesevimab exceeds 5%, as determined by FDA. A list of states, territories, and US jurisdictions in which bamlanivimab and etesevimab are and are not currently authorized is available on the following FDA website: https://www.fda.gov/media/151719/download .1,2

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 together.1

Clinical Worsening After Bamlanivimab and Etesevimab Administration

Clinical worsening of COVID-19 after administration of bamlanivimab and etesevimab together 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.1

Some of these events required hospitalization. It is not known if these events were related to bamlanivimab and etesevimab use or were due to progression of COVID-19.1

Side Effects

Adverse events have been reported with bamlanivimab and etesevimab.1

Additional AEs associated with bamlanivimab and etesevimab, some of which may be serious, may become apparent with more widespread use.1

Overall Safety Summary

Clinical Trial Experience

The safety of bamlanivimab administered with etesevimab is primarily based on exposure of approximately 1400 ambulatory (non-hospitalized) patients who received doses of bamlanivimab and etesevimab together, at the recommended dose or higher, in BLAZE-1 and BLAZE-4. Bamlanivimab and etesevimab at the authorized doses of 700 mg and 1,400 mg have been administered together to approximately 800 subjects in clinical trials.1

The most common TEAEs in the bamlanivimab and etesevimab treatment group in BLAZE-1 and BLAZE-4 included

  • nausea,
  • dizziness, and
  • pruritis.1

No TEAEs occurred in >1% of participants and the rates were comparable in the treatment and placebo groups.1

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.

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-19.3,4

BLAZEa Clinical Trial Designs1,3-5

 

BLAZE-1 Phase 2 (NCT04427501)

BLAZE-1 Phase 3 (NCT04427501)

BLAZE-4 Phase 2 (NCT04634409)

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

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

Percentage of patients with SARS-CoV-2 Viral Load Greater than 5.27 at day 7.

Treatment arms included in analyses

Patients randomized to IV infusion of

  • bamlanivimab alone 700 mg (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)

Patients randomized to IV infusion of

  • bamlanivimab 700 mg and etesevimab 1400 mg together (n=511), or
  • placebo (n=258)

Patients 18-64 years old randomized to IV infusion of

  • bamlanivimab 700 mg alone 
  • bamlanivimab and etesevimab together, dosed at
    • BAM 700 mg + ETE 1400 mg 
    • BAM 2800 mg + ETE 2800mg , or
  • placebo 

Abbreviations: 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.1BLAZE Clinical Trials Baseline Demographics and Disease Characteristics provides information by study.

BLAZE Clinical Trials Baseline Demographics and Disease Characteristics1

 

BLAZE-1 Phase 2

BLAZE-1 Phase 3

BLAZE-4 Phase 2

Median age, years

45

56

39

≥ 65 years old

12%

31%

1%

Female

55%

52%

50%

White

89%

87%

87%

Hispanic or Latino

43%

29%

29%

Black or African American

6%

8%

6%

High-risk for severe COVID-19 illnessa

42%

100%

8%

Mild COVID-19

78%

77%

84%

Moderate COVID-19

22%

23%

16%

Mean duration of symptoms, days

4

4

Mean viral load by CT

24

24

25

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: Summary of Safety Results

BLAZE-1 Phase 3 Safety Data

Treatment-emergent Adverse Events Reported in ≥ 2 Patients Treated with Bamlanivimab and Etesevimab presents reported TEAEs from an integrated safety analysis set of pooled data from BLAZE-1 and BLAZE-4 (with data through March 12, 2021) and included patients treated with 

  • bamlanivimab and etesevimab at the authorized doses of 700 mg and 1400 mg or higher (N=1400), or
  • placebo (N=985).6
Treatment-emergent Adverse Events Reported in ≥ 2 Patients Treated with Bamlanivimab and Etesevimab6

MedDRA System Organ Class

Preferred Term 

Placebo (N=985) 
n (%)

BAM+ETE (N=1400)a
n (%)

Gastrointestinal disorders

20 (2.0)

32 (2.3) 

Nausea

6 (0.6)

12 (0.9)

Gastroesophageal reflux disease

1 (0.1)

5 (0.4)

Vomiting 

3 (0.3)

5 (0.4)

Constipation 

3 (0.3)

3 (0.2)

Diarrhea

3 (0.3)

3 (0.2)

Abdominal pain 

2 (0.2)

2 (0.1)

Dyspepsia

1 (0.1)

2 (0.1) 

Nervous System disorders

16 (1.6)

27 (1.9)

Dizziness

4 (0.4)

11 (0.8)

Headache

1 (0.1)

3 (0.2)

Paresthesia

4 (0.4)

3 (0.2)

Dysgeusia

1 (0.1)

2 (0.1)

Presyncope

0

2 (0.1)

Sciatica

0

2 (0.1)

Syncope

1 (0.1)

2 (0.1)

Tremor

0

2 (0.1)

Infections and Infestations

22 (2.2)

25 (1.8)

Urinary Tract infections

2 (0.2)

7 (0.5)

Pneumonia

3 (0.3)

2 (0.1)

Sinusitis

2 (0.2)

2 (0.1)

Skin and Subcutaneous Tissue disorders

16 (1.6)

24 (1.7) 

Rash

6 (0.6)

9 (0.6)

Pruritus 

1 (0.1)

8 (0.6)

Urticaria 

1 (0.1)

4 (0.3)

General disorders and administration site conditions

9 (0.9)

17 (1.2) 

Pyrexia

0

4 (0.3)

Chest discomfort

0

3 (0.2)

Extravasation 

0

3 (0.2) 

Investigations

8 (0.8)

17 (1.2)

Liver function test increased 

3 (0.3)

6 (0.4)

C-reactive protein increased

1 (0.1)

3 (0.2)

Lipase increased 

1 (0.1)

2 (0.1)

Respiratory, thoracic and mediastinal disorders 

7 (0.7)

16 (1.1)

Rhinalgia

0

3 (0.2)

Asthma

1 (0.1) 

2 (0.1) 

Oropharyngeal pain 

0

2 (0.1) 

Sinus congestion 

1 (0.1) 

2 (0.1) 

Injury, poisoning and procedural complications

3 (0.3)

15 (1.1)

Fall 

1 (0.1)

3 (0.2)

Infusion related reactions 

0

3 (0.2)

Skin laceration 

0

2 (0.1)

Metabolism and nutrition disorders

8 (0.8)

14 (1.0)

Hyperglycemia 

0

2 (0.1)

Hyperlipidemia

1 (0.1)

2 (0.1) 

Type 2 diabetes mellitus

1 (0.1)

2 (0.1) 

Musculoskeletal and connective tissue disorders

12 (1.2)

10 (0.7)

Arthralgia 

2 (0.2)

3 (0.2) 

Back pain 

2 (0.2)

2 (0.1)

Muscular weakness 

0

2 (0.1) 

Vascular disorders 

3 (0.3)

8 (0.6) 

Hypertension 

2 (0.2)

4 (0.3)

Cardiac disorders

5 (0.5)

6 (0.4) 

Acute myocardial infarction

0

2 (0.1) 

Blood and lymphatic system disorders

2 (0.2)

5 (0.4) 

Anemia 

0

3 (0.2) 

Neutropenia 

0

2 (0.1)

Abbreviations: BAM = Bamlanivimab; ETE= Etesevimab; MedDRA = Medical Dictionary for Regulatory Activities

aDoses of bamlanivimab and etesevimab used for this analysis include the authorized doses of 700 mg and 1400 mg or higher (N=1400), or placebo (N=985).

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.

The data from the undiluted treatment arm supported the addition of shorter infusion times added to the Fact Sheet on 09 February 2021.

Summary of Adverse Events With 30-Minute and 15-Minute Bamlanivimab and Etesevimab Infusion6

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.6

References

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

1Fact sheet for healthcare providers. Emergency Use Authorization (EUA) of bamlanivimab and etesevimab. US Food and Drug Administration (FDA). 2021.

2United States Food and Drug Administration. Bamlanivimab and Etesevimab FDA Emergency Use Authorization Letter. Issued August 27, 2021. Accessed August 27, 2021. http://pi.lilly.com/eua/bam-and-ete-eua-fda-authorization-letter.pdf

3Gottlieb 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: a randomized clinical trial. JAMA. 2021;325(7):632-644. http://dx.doi.org/10.1001/jama.2021.0202

4A 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 April 20, 2021. Accessed April 22, 2021. https://www.clinicaltrials.gov/ct2/show/NCT04427501

5A study of immune system proteins in participants with mild to moderate COVID-19 illness (BLAZE-4). ClinicalTrials.gov identifier: NCT04634409. Updated May 21, 2021. Accessed June 3, 2021. https://clinicaltrials.gov/ct2/show/NCT04634409

6Data on file, Eli Lilly and Company and/or one of its subsidiaries.

Glossary

AE = adverse event

ASPR = Assistant Secretary for Preparedness and Response

BAM = bamlanivimab

ETE = etesevimab

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

US = United States

Date of Last Review: May 14, 2021


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