Bebtelovimab: Package Insert and Label Information

BEBTELOVIMAB- bebtelovimab injection, solution
Eli Lilly and Company

HIGHLIGHTS OF EMERGENCY USE AUTHORIZATION (EUA) These highlights of the EUA do not include all the information needed to use BEBTELOVIMAB under the EUA. See the FULL FACT SHEET FOR HEALTHCARE PROVIDERS for BEBTELOVIMAB. BEBTELOVIMAB injection for intravenous use Original EUA Authorized Date: 02/2022Revised EUA Authorized Date: 08/2022 —————————-RECENT MAJOR CHANGES————————– Dosage and Administration, Dose Preparation and 03/2022Administration (2.3): updated administration materials Use in Specific Populations, Pregnancy (8.1): added hypersensitivity reactions in pregnant women 05/2022 Clinical Pharmacology, Microbiology (12.4): updated 08/2022neutralizing data ——————-EMERGENCY USE AUTHORIZATION——————– The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of bebtelovimab for the treatment of mild-to-moderate coronavirus disease 2019 (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, and
  • for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate. (14.4)
LIMITATIONS OF AUTHORIZED USE
  • Bebtelovimab is not authorized for treatment of mild-to-moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to this drug and regional variant frequency.
    • FDA will monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility, and CDC regional variant frequency data available at: https://covid.cdc.gov/covid-data-tracker/#variant-proportions. (12.4)
    • FDA’s determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs
  • Bebtelovimab is not authorized for use in patients who:
    • are hospitalized due to COVID-19, OR
    • require oxygen therapy and/or respiratory support due to COVID-19, OR
    • require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity.
Bebtelovimab is not approved for any use, including for use as treatment of COVID-19. (1)Bebtelovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bebtelovimab under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.See Full Fact Sheet for Healthcare Providers for the justification for emergency use of drugs during the COVID-19 pandemic, information on available alternatives, and additional information on COVID-19.
————————DOSAGE AND ADMINISTRATION———————– The dosage in adults (18 years and older) and pediatric patients (≥12 years of age and weighing at least 40 kg) is bebtelovimab 175 mg administered as a single intravenous injection over at least 30 seconds. Administer bebtelovimab as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset. (2.1)———————DOSAGE FORMS AND STRENGTHS———————- Injection: 175 mg/2 mL (87.5 mg/mL) in a single-dose vial. (3)——————————-CONTRAINDICATIONS—————————— No contraindications have been identified based on the limited available data for the emergency use of bebtelovimab authorized under this EUA. (4)————————WARNINGS AND PRECAUTIONS———————–
  • Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of other SARS-CoV-2 monoclonal antibodies and could occur with administration of bebtelovimab. If clinically significant hypersensitivity reactions occur, discontinue and initiate appropriate supportive care. Infusion-related reactions may occur up to 24 hours post injection. These reactions may be severe or life threatening. (5.1)
  • Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration: Clinical worsening of COVID-19 after administration of SARS-CoV-2 monoclonal antibody treatment 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 SARS-CoV-2 monoclonal antibody use or were due to progression of COVID-19. (5.2)
  • Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Treatment with bebtelovimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bebtelovimab, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high flow oxygen or mechanical ventilation. (5.3)——————————-ADVERSE REACTIONS—————————— Most common adverse reactions are infusion-related reactions (0.3%), pruritus (0.3%), and rash (0.8%). (6.1)You or your designee must report all SERIOUS ADVERSE EVENTS or MEDICATION ERRORS potentially related to bebtelovimab (1) by submitting FDA Form 3500 online, (2) by downloading this form and then submitting by mail or fax, or (3) contacting the FDA at 1-800-FDA-1088 to request this form. Please also provide a copy of this form to Eli Lilly and Company, Global Patient Safety: Fax: 1-317-277-0853; E-mail: mailindata_gsmtindy@lilly.com; or call 1-855-LillyC19 (1-855-545-5921) to report adverse events. (6.4).——————————–DRUG INTERACTIONS—————————— Bebtelovimab 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. (7)See FACT SHEET FOR PATIENTS, PARENTS, AND CAREGIVERS.
TABLE OF CONTENTS* 1 EMERGENCY USE AUTHORIZATION 2 DOSAGE AND ADMINISTRATION 2.1 Dosage 2.2 Dosage Adjustment in Specific Populations 2.3 Dose Preparation and Administration3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions 5.2 Clinical Worsening After SARS-CoV-2 Monoclonal Antibody Administration 5.3 Limitations of Benefit and Potential for Risk in Patients with Severe COVID-196 ADVERSE REACTIONS 6.1 Adverse Reactions from Clinical Studies 6.4 Required Reporting for Serious Adverse Events and Medication Errors7 DRUG INTERACTIONS 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy 8.2 Lactation 8.4 Pediatric Use 8.5 Geriatric Use 10 OVERDOSAGE 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 12.4 Microbiology13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 13.2 Animal Toxicology and/or Pharmacology14 CLINICAL STUDIES 14.1 Phase 2 Data from the Placebo-Controlled Portion of BLAZE-4 (Low Risk Subjects; Treatment Arms 9-11) 14.2 Phase 2 Data from the Randomized, Open-Label Portion of BLAZE-4 (High Risk Subjects; Treatment Arms 12-13) 14.3 Phase 2 Data from the Non-Randomized, Open-Label Portion of BLAZE-4 (High Risk Subjects; Treatment Arm 14) 14.4 Overall Benefit-Risk Assessment and Limitations of Data Supporting the Benefits of the Product16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION 18 MANUFACTURER INFORMATION * Sections or subsections omitted from the EUA are not listed

FULL FACT SHEET FOR HEALTHCARE PROVIDERS

1 EMERGENCY USE AUTHORIZATION

The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of bebtelovimab for the treatment of mild-to-moderate coronavirus disease 2019 (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 1 for progression to severe COVID-19, including hospitalization or death, and
  • for whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate [see Clinical Studies (14.4)].

LIMITATIONS OF AUTHORIZED USE

  • Bebtelovimab is not authorized for treatment of mild-to-moderate COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant based on available information including variant susceptibility to this drug and regional variant frequency.
    • FDA’s determination and any updates will be available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs.2
  • Bebtelovimab is not authorized for use in patients, who:
    • are hospitalized due to COVID-19, OR
    • require oxygen therapy and/or respiratory support due to COVID-19, OR
    • require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19 and are on chronic oxygen therapy and/or respiratory support due to underlying non-COVID-19 related comorbidity.

Treatment with bebtelovimab has not been studied in patients hospitalized due to COVID-19. Monoclonal antibodies, such as bebtelovimab, 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)].

Bebtelovimab is not FDA-approved for any use, including for use as treatment of COVID-19 [see Emergency Use Authorization (1)].

Bebtelovimab is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use of bebtelovimab 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
For information on medical conditions and factors associated with increased risk for progression to severe COVID-19, see the Centers for Disease Control and Prevention (CDC) website: https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-care/underlyingconditions.html. Healthcare providers should consider the benefit-risk for an individual patient.
2
FDA will monitor conditions to determine whether use in a geographic region is consistent with this scope of authorization, referring to available information, including information on variant susceptibility [see Microbiology (12.4)] , and CDC regional variant frequency data available at: https://covid.cdc.gov/covid-data-tracker/#variant-proportions.

Justification for Emergency Use of Drugs During the COVID-19 Pandemic

There is currently an outbreak of Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2, a novel coronavirus. The Secretary of HHS has declared that:

  • A public health emergency related to COVID-19 has existed since January 27, 2020.
  • Circumstances exist justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic (March 27, 2020 declaration).

An EUA is a FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that there is a public health emergency that affects the national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:

  • The biological agent(s) can cause a serious or life-threatening disease or condition;
  • Based on the totality of the available scientific evidence (including data from adequate and well-controlled clinical trials, if available), it is reasonable to believe that
    • the product may be effective in diagnosing, treating, or preventing the serious or life-threatening disease or condition; and
    • The known and potential benefits of the product — when used to diagnose, prevent, or treat such disease or condition — outweigh the known and potential risks of the product, taking into consideration the material threat posed by the biological agent(s);
  • There is no adequate, approved, and available alternative to the product for diagnosing, preventing, or treating the serious or life-threatening disease or condition.

Information Regarding Available Alternatives for the EUA Authorized Use

Veklury (remdesivir) is FDA-approved for the treatment of 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, who are not hospitalized and have mild-to-moderate COVID-19, and who are at high risk for progression to severe COVID-19, including hospitalization or death. Veklury is administered via intravenous infusion for a total treatment duration of 3 days.

Although Veklury is an approved alternative 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, FDA does not consider Veklury to be an adequate alternative to bebtelovimab for this authorized use because it may not be feasible or practical for certain patients (e.g., it requires a 3-day treatment duration).

Other therapeutics are currently authorized for the same use as bebtelovimab. For additional information on all products authorized for treatment or prevention of COVID-19, please see https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.

For information on clinical studies of bebtelovimab and other therapies for the treatment of COVID-19, see www.clinicaltrials.gov.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

The dosage in adults (18 years and older) and pediatric patients (≥12 years of age and weighing at least 40 kg) is bebtelovimab 175 mg.

Administer bebtelovimab as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset.

Bebtelovimab must be administered as a single intravenous injection over at least 30 seconds.

2.2 Dosage Adjustment in Specific Populations

No dosage adjustment is recommended in pregnant or lactating individuals, in geriatrics, in individuals with renal impairment, or in individuals with mild hepatic impairment [see Clinical Pharmacology (12.3)].

2.3 Dose Preparation and Administration

General Information

  • Bebtelovimab should be prepared by a qualified healthcare professional using aseptic technique.
  • Inspect bebtelovimab vial visually for particulate matter and discoloration. Bebtelovimab is clear to opalescent and colorless to slightly yellow to slightly brown solution. Discard the vial if the solution is cloudy, discolored or visible particles are observed.
  • Bebtelovimab may only be administered in settings in which healthcare providers have immediate access to medications to treat a severe infusion reaction, such as anaphylaxis, and the ability to activate the emergency medical system (EMS), as necessary.
  • Clinically monitor patients for possible infusion-related reactions during administration and observe patients for at least 1 hour after injection is complete.

Materials Needed for Administration

  • 1 bebtelovimab vial (175 mg/2 mL)
  • 1 disposable polypropylene dosing syringe capable of holding 2 mL
  • 0.9% Sodium Chloride Injection for flushing
  • Optional: 1 syringe extension set made of polyethylene or polyvinylchloride with or without di-ethylhexylphthalate (DEHP)

Preparation

  • Remove bebtelovimab 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 vial. Inspect the vial.
  • Withdraw 2 mL from the vial into the disposable syringe.
  • Discard any product remaining in the vial.
  • This product is preservative-free and therefore, should be administered immediately.
    • If immediate administration is not possible, store the syringe 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]). If refrigerated, allow the prepared syringe to equilibrate to room temperature for approximately 20 minutes prior to administration.
  • If used, attach and prime the syringe extension set.
  • Administer the entire contents of the syringe via IV injection over at least 30 seconds.
  • After the entire contents of the syringe have been administered, flush the injection line with 0.9% Sodium Chloride to ensure delivery of the required dose.

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