BAMLANIVIMAB injection, solution

Bamlanivimab by

Drug Labeling and Warnings

Bamlanivimab by is a Prescription medication manufactured, distributed, or labeled by Eli Lilly and Company. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • CONTACT INFORMATION

    For additional information visit

    www.bamlanivimab.com

    If you have questions, please contact

    1-855-LillyC19 (1-855-545-5921)

    END SHORT VERSION FACT SHEET

    Long Version Begins on Next Page

  • FULL EUA PRESCRIBING INFORMATION

    FULL EUA PRESCRIBING INFORMATION: CONTENTS*
    11.2 Lactation
    1 AUTHORIZED USE
    11.3 Pediatric Use
    2 DOSAGE AND ADMINISTRATION
    11.4 Geriatric Use
    2.1 Patient Selection
    11.5 Renal Impairment
    2.2 Dosage
    11.6 Hepatic Impairment
    2.3 Dosage Adjustment in Specific Populations
    11.7 Other Specific Populations
    2.4 Dose Preparation and Administration
    12 OVERDOSAGE
    3 DOSAGE FORMS AND STRENGTHS
    13 DESCRIPTION
    4 CONTRAINDICATIONS
    14 CLINICAL PHARMACOLOGY
    5 WARNINGS AND PRECAUTIONS
    14.1 Mechanism of Action
    5.1 Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions
    14.2 Pharmacodynamics
    5.2 Clinical Worsening After Bamlanivimab Administration
    14.3 Pharmacokinetics
    5.3 Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19
    15 MICROBIOLOGY/RESISTANCE INFORMATION
    6 OVERALL SAFETY SUMMARY
    16 NONCLINICAL TOXICOLOGY
    6.1 Clinical Trials Experience
    17 ANIMAL PHARMACOLOGIC AND EFFICACY DATA
    7 PATIENT MONITORING RECOMMENDATIONS
    18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA
    8 ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS
    18.1 Mild to Moderate COVID-19 (BLAZE-1)
    9 OTHER REPORTING REQUIREMENTS
    19 HOW SUPPLIED/STORAGE AND HANDLING
    10 DRUG INTERACTIONS
    20 PATIENT COUNSELING INFORMATION
    11 USE IN SPECIFIC POPULATIONS
    21 CONTACT INFORMATION
    11.1 Pregnancy
    * Sections or subsections omitted from the full prescribing information are not listed.
  • 1 AUTHORIZED USE

    Bamlanivimab is authorized for use under an EUA for 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.

    LIMITATIONS OF AUTHORIZED USE

    • Bamlanivimab is not authorized for use in patients:
      • who are hospitalized due to COVID-19, OR
      • who require oxygen therapy due to COVID-19, OR
      • who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
    • Benefit of treatment with bamlanivimab has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation [see Warnings and Precautions (5.3)].
  • 2 DOSAGE AND ADMINISTRATION

    2.1 Patient Selection

    Bamlanivimab should be administered as soon as possible after positive viral test for SARS-CoV-2 and within 10 days of symptom onset in adults and pediatric patients (12 years of age and older weighing at least 40 kg), who are at high risk for progressing to severe COVID-19 and/or hospitalization.

    High risk is defined as patients who meet at least one of the following criteria:

    • Have a body mass index (BMI) ≥35
    • Have chronic kidney disease
    • Have diabetes
    • Have immunosuppressive disease
    • Are currently receiving immunosuppressive treatment
    • Are ≥65 years of age
    • Are ≥55 years of age 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 on CDC growth charts, https://www.cdc.gov/growthcharts/clinical_charts.htm, OR
      • sickle cell disease, OR
      • congenital or acquired heart disease, OR
      • neurodevelopmental disorders, for example, cerebral palsy, OR
      • a medical-related technological dependence, for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID-19), OR
      • asthma, reactive airway or other chronic respiratory disease that requires daily medication for control.

    2.2 Dosage

    The dosage of bamlanivimab in adults and pediatric patients (12 years of age and older weighing at least 40 kg) is:

    • bamlanivimab 700 mg.

    Administer bamlanivimab as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 10 days of symptom onset.

    Bamlanivimab must be diluted and administered as a single IV infusion.

    2.3 Dosage Adjustment in Specific Populations

    Pregnancy or Lactation

    No dosage adjustment is recommended in pregnant or lactating women [see Use in Specific Populations (11.1, 11.2)].

    Pediatric Use

    No dosage adjustment is recommended in pediatric patients who weigh at least 40 kg and are 12 years of age and older. Bamlanivimab is not authorized for patients weighing less than 40 kg or those less than 12 years of age [see Use in Specific Populations (11.3)].

    Geriatric Use

    No dosage adjustment is recommended in geriatric patients [see Use in Specific Populations (11.4)].

    Renal Impairment

    No dosage adjustment is recommended in patients with renal impairment [see Use in Specific Populations (11.5)].

    Hepatic Impairment

    No dosage adjustment is recommended in patients with mild hepatic impairment. Bamlanivimab has not been studied in patients with moderate or severe hepatic impairment [see Use in Specific Populations (11.6)].

    2.4 Dose Preparation and Administration

    Preparation

    Bamlanivimab solution for infusion should be prepared by a qualified healthcare professional using aseptic technique:

    • Gather the materials for preparation:
      • Polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC, sterile prefilled infusion bag. Choose one of the following sizes:
        • Prefilled 50 mL, 100 mL, 150 mL, or 250 mL infusion bag containing 0.9% Sodium Chloride Injection (see Table 1).
      • One 20 mL vial of bamlanivimab (700 mg/20 mL).
    • Remove one bamlanivimab vial from refrigerated storage and allow to equilibrate to room temperature for approximately 20 minutes before preparation. Do not expose to direct heat. Do not shake the vial.
    • Inspect bamlanivimab visually for particulate matter and discoloration.
      • Bamlanivimab is a clear to opalescent and colorless to slightly yellow to slightly brown solution.
    • Withdraw 20 mL bamlanivimab from one 20 mL vial and inject into a prefilled infusion bag containing 0.9% Sodium Chloride Injection (see Table 1).
    • Discard any product remaining in the vial.
    • Gently invert IV bag by hand approximately 10 times to mix. Do not shake.
    • This product is preservative-free and therefore, the diluted infusion solution should be administered immediately.
      • If immediate administration is not possible, store the diluted bamlanivimab infusion solution for up to 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]) and up to 7 hours at room temperature (20°C to 25°C [68°F to 77°F]) including infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration.

    Administration

    Bamlanivimab infusion solution should be administered by a qualified healthcare professional.

    • Gather the materials for infusion:
      • Polyvinyl chloride (PVC) or polyethylene (PE)-lined PVC infusion set
      • Use of an in-line or add-on 0.20/0.22 micron polyethersulfone (PES) filter is strongly recommended.
    • Attach the infusion set to the IV bag.
    • Prime the infusion set.
    • Administer the entire infusion solution in the bag via pump or gravity according to the size of infusion bag used (see Table 1). Due to potential overfill of prefilled saline bags, the entire infusion solution in the bag should be administered to avoid underdosage.
    • The prepared infusion solution should not be administered simultaneously with any other medication. The compatibility of bamlanivimab with IV solutions and medications other than 0.9% Sodium Chloride Injection is not known.
    • Once infusion is complete, flush the tubing with 0.9% Sodium Chloride to ensure delivery of the required dose.
    • Clinically monitor patients during administration and observe patients for at least 1 hour after infusion is complete.
    • If the infusion must be discontinued due to an infusion reaction, discard any unused product.
    • The use of closed system transfer devices (CSTDs), elastomeric pumps, and pneumatic transport with bamlanivimab has not been studied.
    Table 1: Recommended Dilution and Administration Instructions for Bamlanivimaba

    a 700 mg of bamlanivimab (20 mL) is added to an infusion bag and administered as a single intravenous infusion.

    Drug: Add 20 mL of bamlanivimab (1 vial) to a prefilled infusion bag and administer as instructed below
    Size of prefilled 0.9% Sodium Chloride infusion bagMaximum Infusion RateMinimum Infusion Time
    50 mL 270 mL/hr 16 minutes
    100 mL 270 mL/hr 27 minutes
    150 mL 270 mL/hr 38 minutes
    250 mL 270 mL/hr 60 minutes

    Storage

    This product is preservative-free and therefore, the diluted infusion solution should be administered immediately. If immediate administration is not possible, store the diluted bamlanivimab infusion solution for up to 24 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]) and up to 7 hours at room temperature (20°C to 25°C [68°F to 77°F]) including infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature for approximately 20 minutes prior to administration.

  • 3 DOSAGE FORMS AND STRENGTHS

    Bamlanivimab is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution available as:

    • Injection: 700 mg/20 mL (35 mg/mL) in a single-dose vial.
  • 4 CONTRAINDICATIONS

    None.

  • 5 WARNINGS AND PRECAUTIONS

    There are limited clinical data available for bamlanivimab. Serious and unexpected adverse events may occur that have not been previously reported with bamlanivimab use.

    5.1 Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions

    Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of bamlanivimab. If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

    Infusion-related reactions have been observed with administration of bamlanivimab. These reactions may be severe or life threatening.

    Signs and symptoms of infusion related reactions may include:

    • fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (e.g., atrial fibrillation, sinus tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, nausea, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, dizziness and diaphoresis.

    If an infusion-related reaction occurs, consider slowing or stopping the infusion and administer appropriate medications and/or supportive care.

    5.2 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. Some of these events required hospitalization. It is not known if these events were related to bamlanivimab use or were due to progression of COVID-19.

    5.3 Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19

    Benefit of treatment with bamlanivimab has not been observed in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bamlanivimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. Therefore, bamlanivimab is not authorized for use in patients [see Limitations of Authorized Use]:

    • who are hospitalized due to COVID-19, OR
    • who require oxygen therapy due to COVID-19, OR
    • who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity.
  • 6 OVERALL SAFETY SUMMARY

    Over 1350 subjects have been exposed to bamlanivimab in clinical trials in both hospitalized and non-hospitalized patients.

    6.1 Clinical Trials Experience

    The safety of bamlanivimab is based on interim data from one Phase 2 trial of 465 ambulatory (non-hospitalized) subjects with COVID-19.

    BLAZE-1 is a randomized, double-blind, placebo-controlled clinical trial in ambulatory adults with mild to moderate COVID-19 symptoms who had sample collection for the first positive SARS-CoV-2 viral infection determination within 3 days prior to the start of the infusion. Subjects were treated with a single infusion of bamlanivimab at doses of 700 mg (N=101), 2,800 mg (N=107), or 7,000 mg (N=101) or placebo (N=156).

    Based on data from 309 bamlanivimab-treated subjects followed for at least 28 days after treatment, adverse events occurred in 23% bamlanivimab-treated subjects and 26% of placebo-treated subjects. Serious adverse events occurred in 1 placebo-treated subject (1%) and in no bamlanivimab-treated subjects.

    The most commonly reported adverse event was nausea. Table 2 shows adverse events reported in at least 1% of patients in any treatment group. Bamlanivimab is not authorized at doses of 2,800 mg or 7,000 mg.

    Table 2: Treatment-emergent Adverse Events Reported in at Least 1% of All Subjects in BLAZE-1
    Preferred term
    Placebo
    N=156

    %
    Bamlanivimab
    700 mg
    N=101

    %
    2,800 mg
    N=107

    %
    7,000 mg
    N=101

    %
    Total
    N=309

    %
    Nausea 4% 3% 4% 5% 4%
    Diarrhea 5% 1% 2% 7% 3%
    Dizziness 2% 3% 3% 3% 3%
    Headache 2% 3% 2% 0% 2%
    Pruritus 1% 2% 3% 0% 2%
    Vomiting 3% 1% 3% 1% 2%

    Hypersensitivity Including Anaphylaxis and Infusion-related Reactions:

    Across ongoing, blinded clinical trials, a case of anaphylaxis and other cases of serious infusion-related reactions were reported with infusion of bamlanivimab. The infusions were stopped. All reactions required treatment, one required epinephrine. All events resolved.

    Immediate non-serious hypersensitivity events were noted for 2% of bamlanivimab-treated subjects and 1% of placebo-treated subjects in BLAZE-1. Reported events of pruritus, flushing and hypersensitivity were mild with one case of face swelling which was moderate. All events resolved [see Warnings and Precautions (5.1)].

  • 7 PATIENT MONITORING RECOMMENDATIONS

    Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion is complete [see Warnings and Precautions (5.1) and Clinical Trials Experience (6.1)].

  • 8 ADVERSE REACTIONS AND MEDICATION ERRORS REPORTING REQUIREMENTS AND INSTRUCTIONS

    Clinical trials evaluating the safety of bamlanivimab are ongoing [see Overall Safety Summary (6)].

    Completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory. The prescribing healthcare provider and/or the provider's designee are/is responsible for the mandatory reporting of all medication errors and the following serious adverse events occurring during bamlanivimab use and considered to be potentially related to bamlanivimab. These adverse events must be reported within 7 calendar days from the onset of the event:

    • death;
    • a life-threatening adverse event;
    • 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;
    • a medical or surgical intervention to prevent death, a life-threatening event, hospitalization, disability, or congenital anomaly.

    If a serious and unexpected adverse event occurs and appears to be associated with the use of bamlanivimab, the prescribing healthcare provider and/or the provider's designee should complete and submit a MedWatch form to FDA using one of the following methods:

    • Complete and submit the report online: www.fda.gov/medwatch/report.htm, or
    • Use a postage-paid Form FDA 3500 (available at http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf) and returning by mail (MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787), or by fax (1-800-FDA- 0178), or
    • Call 1-800-FDA-1088 to request a reporting form

    IMPORTANT: When reporting adverse events or medication errors to MedWatch, please complete the entire form with detailed information. It is important that the information reported to FDA be as detailed and complete as possible. Information to include:

    • Patient demographics (e.g., patient initials, date of birth)
    • Pertinent medical history
    • Pertinent details regarding adverse events and course of illness
    • Concomitant medications
    • Timing of adverse event(s) in relationship to administration of bamlanivimab
    • Pertinent laboratory and virology information
    • Outcome of the event and any additional follow-up information if it is available at the time of the MedWatch report. Subsequent reporting of follow-up information should be completed if additional details become available.

    The following steps are highlighted to provide the necessary information for safety tracking:

    • In section A, box 1, provide the patient's initials in the Patient Identifier
    • In section A, box 2, provide the patient's date of birth
    • In section B, box 5, description of the event:
      • Write “Bamlanivimab treatment under Emergency Use Authorization (EUA)” as the first line
      • Provide a detailed report of medication error and/or adverse event. It is important to provide detailed information regarding the patient and adverse event/medication error for ongoing safety evaluation of this unapproved drug. Please see information to include listed above.
    • In section G, box 1, name and address:
      • Provide the name and contact information of the prescribing healthcare provider or institutional designee who is responsible for the report.
      • Provide the address of the treating institution (NOT the healthcare provider's office address).
  • 9 OTHER REPORTING REQUIREMENTS

    • Healthcare facilities and providers must report therapeutics information and utilization data through HHS Protect, Teletracking or National Healthcare Safety Network (NHSN) as directed by the U.S. Department of Health and Human Services.
    • In addition, please provide a copy of all FDA MedWatch forms to:
    •   Eli Lilly and Company, Global Patient Safety
    •   Fax: 1-317-277-0853
    •   E-mail: mailindata_gsmtindy@lilly.com
    •   Or call Eli Lilly and Company at 1-855-LillyC19 (1-855-545-5921) to report adverse events.
  • 10 DRUG INTERACTIONS

    Bamlanivimab is not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

  • 11 USE IN SPECIFIC POPULATIONS

    11.1 Pregnancy

    Risk Summary

    There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Bamlanivimab should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus.

    Nonclinical reproductive toxicity studies have not been performed with bamlanivimab. In a tissue cross reactivity study with bamlanivimab using human fetal tissues, no binding of clinical concern was detected. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placental barrier; therefore, bamlanivimab has the potential to be transferred from the mother to the developing fetus. It is unknown whether the potential transfer of bamlanivimab provides any treatment benefit or risk to the developing fetus.

    The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

    11.2 Lactation

    Risk Summary

    There are no available data on the presence of bamlanivimab in human or animal milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for bamlanivimab and any potential adverse effects on the breastfed child from bamlanivimab or from the underlying maternal condition. Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19.

    11.3 Pediatric Use

    The safety and effectiveness of bamlanivimab have not been assessed in pediatric patients. The recommended dosing regimen is expected to result in comparable serum exposures of bamlanivimab in patients 12 years of age and older and weighing at least 40 kg as observed in adults, based on a pharmacokinetic (PK) modeling approach which accounted for effect of body weight changes associated with age on clearance and volume of distribution.

    11.4 Geriatric Use

    Of the 309 patients receiving bamlanivimab in BLAZE-1, 11% were 65 years of age and older and 3% were 75 years of age and older. Based on population PK analyses, there is no difference in PK in geriatric patients compared to younger patients.

    11.5 Renal Impairment

    Bamlanivimab is not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of bamlanivimab.

    11.6 Hepatic Impairment

    Based on population PK analysis, there is no significant difference in PK of bamlanivimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bamlanivimab has not been studied in patients with moderate or severe hepatic impairment.

    11.7 Other Specific Populations

    Based on population PK analysis, the PK of bamlanivimab was not affected by sex, race, or disease severity. Body weight had no clinically relevant effect on the PK of bamlanivimab in adults with COVID-19 over the body weight range of 41 kg to 173 kg.

  • 12 OVERDOSAGE

    Doses up to 7,000 mg (10 times the recommended dose) have been administered in clinical trials without dose-limiting toxicity. Treatment of overdose with bamlanivimab should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient. There is no specific antidote for overdose with bamlanivimab.

  • 13 DESCRIPTION

    Bamlanivimab is a human immunoglobulin G-1 (IgG1 variant) monoclonal antibody consisting of 2 identical light chain polypeptides composed of 214 amino acids each and 2 identical heavy chain polypeptides composed of 455 amino acids produced by a Chinese Hamster Ovary (CHO) cell line and molecular weight of 146 kDa.

    Bamlanivimab injection is a sterile, preservative-free, clear to opalescent and colorless to slightly yellow to slightly brown solution in a single-dose vial for intravenous infusion after dilution.

    Each mL contains 35 mg of bamlanivimab, and L-histidine (0.4 mg), L-histidine hydrochloride monohydrate (0.6 mg), sodium chloride (2.9 mg), sucrose (60 mg), polysorbate 80 (0.5 mg), and Water for Injection. The bamlanivimab solution has a pH range of 5.5-6.5.

  • 14 CLINICAL PHARMACOLOGY

    14.1 Mechanism of Action

    Bamlanivimab is a recombinant neutralizing human IgG1K monoclonal antibody (mAb) to the spike protein of SARS-CoV-2, and is unmodified in the Fc region. Bamlanivimab binds to spike protein with a dissociation constant KD = 0.071 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.025 μg/mL.

    14.2 Pharmacodynamics

    A Phase 2 trial evaluated bamlanivimab over a dose range of 1 to 10 times the recommended dose (700 to 7000 mg) of bamlanivimab in patients with mild to moderate COVID-19. A flat exposure-response relationship for efficacy was identified for bamlanivimab within this dose range, based on viral load and clinical outcomes.

    14.3 Pharmacokinetics

    The pharmacokinetic profile of bamlanivimab is linear and dose-proportional between 700 mg and 7000 mg following a single IV administration. There were no differences in PK of bamlanivimab between severe/moderate participants who were hospitalized and mild/moderate ambulatory participants.

    Absorption

    The mean maximum concentration (Cmax) of 700 mg bamlanivimab was 196 μg/mL (90% CI: 102 to 378 μg/mL) following approximately 1 hour 700 mg IV infusion.

    Distribution

    Bamlanivimab mean volume of distribution (V) was 2.87 L and 2.71 L for the central and peripheral compartments, respectively. The between subject variability was 23.2% CV.

    Metabolism

    Bamlanivimab is expected to be degraded into small peptides and component amino acids via catabolic pathways in the same manner as endogenous IgG antibodies.

    Elimination

    Bamlanivimab clearance (CL) was 0.27 L/hr (between subject variability 22.3% CV) and the mean apparent terminal elimination half-life was 17.6 days (between subject variability 15.8% CV). Following a single 700 mg IV dose, bamlanivimab was quantifiable for at least 29 days. The mean concentration was 22 μg/mL (90% CI: 10.7 to 41.6 μg/mL) on Day 29.

    Special Populations:

    The PK profile of bamlanivimab was not affected by age, sex, race, or disease severity based on a population PK analysis. Body weight had no clinically relevant effect on the PK of bamlanivimab in adults with COVID-19 over the body weight range of 41 kg to 173 kg [see Use in Specific Populations (11.4, 11.7)].

    Pediatric population

    The PK of bamlanivimab in pediatric patients have not been evaluated.

    Using modeling and simulation, the recommended dosing regimen is expected to result in comparable plasma exposures of bamlanivimab in pediatric patients ages 12 years of age or older who weigh at least 40 kg as observed in adult patients [see Use in Specific Populations (11.3)].

    Patients with renal impairment

    Bamlanivimab is not eliminated intact in the urine, thus renal impairment is not expected to affect the exposure of bamlanivimab [see Use in Specific Populations (11.5)].

    Patients with hepatic impairment

    Based on population PK analysis, there is no significant difference in PK of bamlanivimab in patients with mild hepatic impairment compared to patients with normal hepatic function. Bamlanivimab has not been studied in patients with moderate or severe hepatic impairment [see Use in Specific Populations (11.6)].

    Drug interactions:

    Bamlanivimab is not renally excreted or metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

  • 15 MICROBIOLOGY/RESISTANCE INFORMATION

    Antiviral Activity

    The cell culture neutralization activity of bamlanivimab against SARS-CoV-2 was measured in a dose-response model quantifying plaque reduction using cultured Vero E6 cells. Bamlanivimab neutralized the USA/WA/1/2020 isolate of SARS-CoV-2 with an estimated EC50 value = 0.14 nM (0.02 μg/mL).

    Bamlanivimab demonstrated antibody-dependent cell-mediated cytotoxicity on reporter Jurkat cells expressing FcγRIIIa following engagement with target cells expressing spike protein. Bamlanivimab did not elicit complement-dependent cytotoxicity activity in cell-based assays.

    Antibody Dependent Enhancement (ADE) of Infection

    The risk that bamlanivimab could mediate viral uptake and replication by immune cells was studied in THP-1 and Raji cell lines and primary human macrophages. This experiment did not demonstrate productive viral infection in immune cells exposed to SARS CoV-2 at concentrations of bamlanivimab down to 100-fold below the EC50 value.

    Antiviral Resistance

    There is a potential risk of treatment failure due to the development of viral variants that are resistant to bamlanivimab.

    Non-clinical studies using serial passage of SARS-CoV-2 and directed evolution of the spike protein identified E484K, F490S, Q493R and S494P, amino acid substitutions in the spike protein receptor binding domain, that had reduced susceptibility to bamlanivimab as determined in neutralization assays using SARS-CoV-2 (F490S and S494P: >485-fold and >71-fold reduction, respectively) and/or vesicular stomatitis virus-based pseudovirus (all variants >100-fold reduction).

    Given increasing global prevalence of N501Y, pseudovirus assays were conducted and no loss in susceptibility to bamlanivimab was seen with this substitution. Bamlanivimab retained activity against pseudovirus expressing del69-70 + N501Y found in the B.1.1.7 variant (UK origin).

    Genotypic and phenotypic testing are ongoing to monitor for potential bamlanivimab-resistance-associated spike variations in clinical trials. Known bamlanivimab-resistant variants at baseline were observed at a frequency of 0.27% (1/375) in the clinical trial BLAZE-1. In the same trial, treatment-emergent variants were detected at spike protein amino acid positions E484, F490 and S494, and included E484A/D/G/K/Q/V, F490L/S/V and S494L/P; only E484K/Q, F490S and S494P have been assessed phenotypically to date. Considering all variants detected at positions E484, F490 and S494, 9.2% (9/98) and 6.1% (6/98) of participants in the 700 mg bamlanivimab arm harbored such a variant post-baseline at ≥15% and ≥50% allele fractions, respectively, compared with 8.2% (8/97) and 4.1% (4/97), respectively, of participants in the placebo arm. Most of these variants were first detected on Day 7 following treatment initiation and many were detected only at a single time point (700 mg arm: 5/9 and 2/6 at ≥15% and ≥50% allele fractions, respectively; placebo arm: 8/8 and 4/4, respectively). For the 700 mg bamlanivimab arm, these variants were detected more frequently in high-risk participants (14.0% [6/43] and 9.3% [4/43] at ≥15% and ≥50% allele fractions, respectively, vs 2.4% [1/41] and 0% [0/41], respectively, in the placebo arm). The clinical relevance of these findings is not known.

    It is possible that bamlanivimab resistance-associated variants could have cross-resistance to other mAbs targeting the receptor binding domain of SARS-CoV-2. The clinical impact is not known.

    Immune Response Attenuation

    There is a theoretical risk that antibody administration may attenuate the endogenous immune response to SARS-CoV-2 and make patients more susceptible to re-infection.

  • 16 NONCLINICAL TOXICOLOGY

    Carcinogenesis, mutagenesis, and reproductive toxicology studies with bamlanivimab have not been conducted.

    In toxicology studies in rats, bamlanivimab had no adverse effects when administered intravenously. Non-adverse increases in neutrophils were observed.

    In tissue cross reactivity studies using human adult and fetal tissues, no binding of clinical concern was detected.

  • 17 ANIMAL PHARMACOLOGIC AND EFFICACY DATA

    In Vivo Efficacy Pharmacology

    Prophylactic administration of bamlanivimab to female Rhesus macaques (n=3 or 4 per group) resulted in 1 to 4 log10 decreases in viral load (genomic RNA) and viral replication (sub-genomic RNA) in bronchoalveolar lavage samples relative to control animals, but less of an impact on viral RNA in throat and nasal swabs following SARS-CoV-2 inoculation. The applicability of these findings to a prophylaxis or treatment setting is not known.

  • 18 CLINICAL TRIAL RESULTS AND SUPPORTING DATA FOR EUA

    18.1 Mild to Moderate COVID-19 (BLAZE-1)

    The data supporting this EUA are based on an interim analysis from BLAZE-1 that occurred after all enrolled subjects completed at least Day 29 of the trial. BLAZE-1 is a randomized, double-blind, placebo-controlled clinical trial studying bamlanivimab for the treatment of subjects with mild to moderate COVID-19 (subjects with COVID-19 symptoms who are not hospitalized). BLAZE-1 enrolled adult patients who were not hospitalized and had at least 1 or more COVID-19 symptoms that were at least mild in severity. Treatment was initiated within 3 days of obtaining the clinical sample for the first positive SARS-CoV-2 viral infection determination. Subjects were treated with a single infusion of bamlanivimab (at doses of 700 mg [N=101], 2,800 mg [N=107], or 7,000 mg [N=101]) or placebo (N=156).

    At baseline, median age was 45 years (with 12% of subjects aged 65 or older); 55% of subjects were female, 88% were White, 44% were Hispanic or Latino, and 6% were Black; 44% of subjects were considered high risk (as defined in Section 2). Subjects had mild (76%) to moderate COVID-19 (24%); the mean duration of symptoms was 5 days; mean viral load by cycle threshold (CT) was 24 at baseline. The baseline demographics and disease characteristics were well balanced across bamlanivimab and placebo treatment groups.

    The pre-specified primary endpoint in this Phase 2 trial was change in viral load from baseline to Day 11 for bamlanivimab versus placebo. Most subjects, including those receiving placebo, effectively cleared virus by Day 11 (Figure 1).

    Figure 1

    Figure 1: SARS-CoV-2 viral load change from baseline by visit.

    While viral load was used to define the primary endpoint in this Phase 2 trial, the most important evidence that bamlanivimab may be effective came from the predefined secondary endpoint of COVID-19-related hospitalizations or emergency room visits within 28 days after treatment. A lower proportion of bamlanivimab-treated subjects progressed to COVID-19-related hospitalization or emergency room visits compared to placebo-treated subjects (Table 3). Results for this endpoint were suggestive of a relatively flat dose-response relationship.

    Table 3: Proportion of Subjects with Events of Hospitalization or Emergency Room Visits within 28 Days After Treatment

    a N = number of treated patients in analysis.

    TreatmentNaEventsProportion of Subjects
    %
    Placebo 156 9 6%
    bamlanivimab 700 mg 101 1 1%
    bamlanivimab 2800 mg 107 2 2%
    bamlanivimab 7000 mg 101 2 2%
    All bamlanivimab doses 309 5 2%

    The absolute risk reduction for bamlanivimab compared to placebo is greater in subjects at higher risk of hospitalization according to the high risk criteria (Table 4).

    Table 4: Proportion of Subjects with Events of Hospitalization or Emergency Room Visits for Subjects at Higher Risk of Hospitalization

    a N = number of treated patients in analysis.

    TreatmentNaEventsProportion of Subjects
    %
    Placebo 69 7 10%
    bamlanivimab 700 mg 46 1 2%
    bamlanivimab 2800 mg 46 1 2%
    bamlanivimab 7000 mg 44 2 5%
    All bamlanivimab doses 136 4 3%

    The median time to symptom improvement as recorded in a trial specific daily symptom diary was 6 days for bamlanivimab-treated subjects, as compared with 8 days for placebo-treated subjects. Symptoms assessed were cough, shortness of breath, feeling feverish, fatigue, body aches and pains, sore throat, chills, and headache. Symptom improvement was defined as symptoms scored as moderate or severe at baseline being scored as mild or absent, and symptoms scored as mild or absent at baseline being scored as absent.

  • 19 HOW SUPPLIED/STORAGE AND HANDLING

    How Supplied

    Bamlanivimab injection is a sterile, preservative-free clear to opalescent and colorless to slightly yellow to slightly brown solution supplied in a single-dose vial.

    Bamlanivimab is supplied as:

    AntibodyConcentrationPackage SizeNDC
    Bamlanivimab 700 mg/20 mL (35 mg/mL) one vial
    per carton
    0002-7910-01

    Storage and Handling

    Bamlanivimab is preservative-free. Discard unused portion.

    Store unopened vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.

    DO NOT FREEZE, SHAKE, OR EXPOSE TO DIRECT LIGHT.

    Solution in vial requires dilution prior to administration. The prepared infusion solution is intended to be used immediately. If immediate administration is not possible, store diluted bamlanivimab infusion solution in the refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours and at room temperature (20°C to 25°C [68°F to 77°F]) for up to 7 hours, including infusion time. If refrigerated, allow the infusion solution to equilibrate to room temperature prior to administration.

  • 20 PATIENT COUNSELING INFORMATION

    Patients treated with bamlanivimab should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, social distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, and frequent handwashing) according to CDC guidelines. Also see Fact Sheet for Patients, Parents and Caregivers.

  • 21 CONTACT INFORMATION

    For additional information visit:
    www.bamlanivimab.com

    If you have questions, please contact:
    1-855-LillyC19 (1-855-545-5921)

    Literature revised February 9, 2021

    Eli Lilly and Company, Indianapolis, IN 46285, USA
    Copyright © 2020, 2021, Eli Lilly and Company. All rights reserved.

    BAM-0006-EUA HCP-20210209

  • PATIENT PACKAGE INSERT

    Fact Sheet for Patients, Parents and Caregivers
    Emergency Use Authorization (EUA) of Bamlanivimab for Coronavirus Disease 2019 (COVID-19)

    You are being given a medicine called bamlanivimab for the treatment of coronavirus disease 2019 (COVID-19). This Fact Sheet contains information to help you understand the potential risks and potential benefits of taking bamlanivimab, which you may receive.

    Receiving bamlanivimab may benefit certain people with COVID-19.

    Read this Fact Sheet for information about bamlanivimab. Talk to your healthcare provider if you have questions. It is your choice to receive bamlanivimab or stop it at any time.

    What is COVID-19?

    COVID-19 is caused by a virus called a coronavirus. People can get COVID-19 through contact with another person who has the virus.

    COVID-19 illnesses have ranged from very mild (including some with no reported symptoms) to severe, including illness resulting in death. While information so far suggests that most COVID-19 illness is mild, serious illness can happen and may cause some of your other medical conditions to become worse. People of all ages with severe, long-lasting (chronic) medical conditions like heart disease, lung disease, and diabetes, for example, seem to be at higher risk of being hospitalized for COVID-19.

    What are the symptoms of COVID-19?

    The symptoms of COVID-19 include fever, cough, and shortness of breath, which may appear 2 to 14 days after exposure. Serious illness including breathing problems can occur and may cause your other medical conditions to become worse.

    What is bamlanivimab?

    Bamlanivimab is an investigational medicine used to treat mild to moderate symptoms of COVID-19 in non-hospitalized adults and adolescents (12 years of age and older who weigh at least 88 pounds (40 kg)), and who are at high risk for developing severe COVID-19 symptoms or the need for hospitalization. Bamlanivimab is investigational because it is still being studied. There is limited information known about the safety or effectiveness of using bamlanivimab to treat people with COVID-19.

    The FDA has authorized the emergency use of bamlanivimab for the treatment of COVID-19 under an Emergency Use Authorization (EUA). For more information on EUA, see the section “What is an Emergency Use Authorization (EUA)?” at the end of this Fact Sheet.

    What should I tell my healthcare provider before I receive bamlanivimab?

    Tell your healthcare provider about all of your medical conditions, including if you:

    • Have any allergies
    • Are pregnant or plan to become pregnant
    • Are breastfeeding or plan to breastfeed
    • Have any serious illnesses
    • Are taking any medications (prescription, over-the-counter, vitamins, and herbal products)

    How will I receive bamlanivimab?

    • Bamlanivimab is given to you through a vein (intravenous or IV).
    • You will receive one dose of bamlanivimab by IV infusion. The infusion will take 16 – 60 minutes or longer. Your healthcare provider will determine the duration of your infusion.

    What are the important possible side effects of bamlanivimab?

    Possible side effects of bamlanivimab are:

    • Allergic reactions. Allergic reactions can happen during and after infusion with bamlanivimab. Tell your healthcare provider right away if you get any of the following signs and symptoms of allergic reactions: fever, chills, nausea, headache, shortness of breath, low or high blood pressure, rapid or slow heart rate, chest discomfort or pain, weakness, confusion, feeling tired, wheezing, swelling of your lips, face, or throat, rash including hives, itching, muscle aches, dizziness, and sweating. These reactions may be severe or life threatening.
    • Worsening symptoms after bamlanivimab: You may experience new or worsening symptoms after infusion, including fever, difficulty breathing, rapid or slow heart rate, tiredness, weakness or confusion. If these occur, contact your healthcare provider or seek immediate medical attention as some of these events have required hospitalization. It is unknown if these events are related to bamlanivimab infusion or are due to the progression of COVID-19.

    The side effects of getting any medicine by vein may include brief pain, bleeding, bruising of the skin, soreness, swelling, and possible infection at the infusion site.

    These are not all the possible side effects of bamlanivimab. Not a lot of people have been given bamlanivimab. Serious and unexpected side effects may happen. Bamlanivimab is still being studied so it is possible that all of the risks are not known at this time.

    It is possible that bamlanivimab could interfere with your body's own ability to fight off a future infection of SARS-CoV-2. Similarly, bamlanivimab may reduce your body's immune response to a vaccine for SARS-CoV-2. Specific studies have not been conducted to address these possible risks. Talk to your healthcare provider if you have any questions.

    What other treatment choices are there?

    Like bamlanivimab, FDA may allow for the emergency use of other medicines to treat people with COVID-19. Go to https://www.covid19treatmentguidelines.nih.gov/ for information on the emergency use of other medicines that are not approved by FDA to treat people with COVID-19. Your healthcare provider may talk with you about clinical trials you may be eligible for.

    It is your choice to be treated or not to be treated with bamlanivimab. Should you decide not to receive bamlanivimab or stop it at any time, it will not change your standard medical care.

    What if I am pregnant or breastfeeding?

    There is limited experience treating pregnant women or breastfeeding mothers with bamlanivimab. For a mother and unborn baby, the benefit of receiving bamlanivimab may be greater than the risk from the treatment. If you are pregnant or breastfeeding, discuss your options and specific situation with your healthcare provider.

    How do I report side effects with bamlanivimab?

    Tell your healthcare provider right away if you have any side effect that bothers you or does not go away.

    Report side effects to FDA MedWatch at www.fda.gov/medwatch, call 1-800-FDA-1088, or contact Eli Lilly and Company at 1-855-LillyC19 (1-855-545-5921).

    How can I learn more?

    • Ask your healthcare provider
    • Visit www.bamlanivimab.com
    • Visit https://www.covid19treatmentguidelines.nih.gov/
    • Contact your local or state public health department

    What is an Emergency Use Authorization (EUA)?

    The United States FDA has made bamlanivimab available under an emergency access mechanism called an EUA. The EUA is supported by a Secretary of Health and Human Service (HHS) declaration that circumstances exist to justify the emergency use of drugs and biological products during the COVID-19 pandemic.

    Bamlanivimab has not undergone the same type of review as an FDA-approved or cleared product. The FDA may issue an EUA when certain criteria are met, which includes that there are no adequate, approved, and available alternatives. In addition, the FDA decision is based on the totality of scientific evidence available showing that it is reasonable to believe that the product meets certain criteria for safety, performance, and labeling and may be effective in treatment of patients during the COVID-19 pandemic. All of these criteria must be met to allow for the product to be used in the treatment of patients during the COVID-19 pandemic.

    The EUA for bamlanivimab is in effect for the duration of the COVID-19 declaration justifying emergency use of these products, unless terminated or revoked (after which the product may no longer be used).

    Literature revised January 28, 2021

    Eli Lilly and Company, Indianapolis, IN 46285, USA
    Copyright © 2020, 2021, Eli Lilly and Company. All rights reserved.

    BAM-0002-EUA PAT-20210128

  • PRINCIPAL DISPLAY PANEL

    PACKAGE LABEL- Bamlanivimab Injection 700 mg/20 mL (35 mg/mL) Vial Carton

    NDC: 0002-7910-01

    bamlanivimab injection

    700 mg/20 mL (35 mg/mL)

    For Intravenous Infusion Only

    Must dilute before use

    Single-Dose Vial: Discard Unused Portion

    For use under Emergency Use Authorization (EUA).

    Lilly

    Bamlanivimab 700mg Carton
  • INGREDIENTS AND APPEARANCE
    BAMLANIVIMAB 
    bamlanivimab injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 0002-7910
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    Bamlanivimab (UNII: 45I6OFJ8QH) (Bamlanivimab - UNII:45I6OFJ8QH) Bamlanivimab35 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    Histidine (UNII: 4QD397987E) 0.35 mg  in 1 mL
    Histidine Monohydrochloride Monohydrate (UNII: X573657P6P) 0.57 mg  in 1 mL
    Sodium Chloride (UNII: 451W47IQ8X) 2.92 mg  in 1 mL
    Sucrose (UNII: C151H8M554) 60 mg  in 1 mL
    Polysorbate 80 (UNII: 6OZP39ZG8H) 0.50 mg  in 1 mL
    Water (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 0002-7910-011 in 1 CARTON11/09/2020
    120 mL in 1 VIAL, SINGLE-DOSE; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    UNAPPROVED DRUG OTHER11/09/2020
    Labeler - Eli Lilly and Company (006421325)
    Registrant - Eli Lilly and Company (006421325)

  • © 2021 FDA.report
    This site is not affiliated with or endorsed by the FDA.