Bebtelovimab (Monograph)

Drug class: Monoclonal Antibodies
- SARS-CoV-2-specific Monoclonal Antibody
- SARS-CoV-2 spike protein-directed attachment inhibitor

Medically reviewed by Drugs.com on Aug 29, 2022. Written by ASHP.

Introduction

Antiviral; recombinant human immunoglobulin G_1λ (IgG_1λ) monoclonal antibody specific for SARS-CoV-2 virus

Uses for Bebtelovimab

Coronavirus Disease 2019 (COVID-19)

Bebtelovimab is being investigated for and has been used for the treatment of mild to moderate coronavirus disease 2019^{† [off-label]} (COVID-19) caused by SARS-CoV-2.

Bebtelovimab is one of several SARS-CoV-2-specific monoclonal antibody regimens being evaluated for the treatment of COVID-19.

Although efficacy and safety of bebtelovimab not definitely established, the drug is available under an FDA emergency use authorization (EUA) for the treatment of mild to moderate COVID-19 in certain nonhospitalized patients who are at high risk for progression to severe COVID-19, including hospitalization or death.

On February 11, 2022, FDA issued an EUA that permits use of bebtelovimab for the treatment of mild to moderate COVID-19 in adults and pediatric patients ≥12 years of age weighing ≥40 kg with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19, including hospitalization or death, and whom alternative COVID-19 treatment options approved or authorized by FDA are not accessible or clinically appropriate.

Consider the benefits versus risks for the individual patient when making treatment decisions regarding use of FDA-authorized SARS-CoV-2-specific monoclonal antibodies, including bebtelovimab. Information on medical conditions and factors associated with increased risk for progression to severe COVID-19 is available at [Web].

Bebtelovimab is not authorized under the EUA for use in patients who are hospitalized due to COVID-19, require oxygen therapy and/or respiratory support due to COVID-19, or are on chronic oxygen therapy and/or respiratory support due to an underlying non-COVID-19-related comorbidity, or require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19. Benefit of treatment with bebtelovimab has not been studied in patients hospitalized due to COVID-19. SARS-CoV-2-specific monoclonal antibodies, such as bebtelovimab, may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

If a patient is hospitalized for reasons other than COVID-19 (e.g., an elective orthopedic procedure) and reports mild to moderate symptoms of COVID-19, confirmed with positive results of a direct SARS-CoV-2 viral test, FDA states that treatment with bebtelovimab may be appropriate if the patient is also at high risk for progression to severe COVID-19 and terms and conditions of the EUA are met.

For additional information, consult the bebtelovimab EUA letter of authorization [Web], letter granting EUA amendment [Web], EUA fact sheet for health care providers [Web] , and EUA fact sheet for patients, parents, and caregivers [Web]

Bebtelovimab is not authorized for treatment of COVID-19 in geographic regions where infection is likely to have been caused by a non-susceptible SARS-CoV-2 variant.

Bebtelovimab is not authorized under the FDA EUA for prevention of COVID-19.

NIH states that there are several therapeutic options for treatment of nonhospitalized adults with COVID-19 who are at high risk of disease progression. When selecting an appropriate treatment, consider factors such as clinical efficacy and availability of the various options, feasibility of administering parenteral medications (i.e., remdesivir), potential for significant drug-drug interactions (e.g., those associated with the use of ritonavir-boosted nirmatrelvir), and regional prevalence of variants of concern.

The NIH COVID-19 Treatment Guidelines Panel provides recommendations on use of anti-SARS-CoV-2 monoclonal antibodies (mAbs) based on current knowledge of the in vitro activities of the available mAb products against currently circulating SARS-CoV-2 variants and subvariants. For the treatment of adults with mild to moderate COVID-19 who do not require hospitalization or supplemental oxygen but are at risk for progression to severe disease, the NIH guideline panel recommends ritonavir-boosted nirmatrelvir or remdesivir, in order of preference. If these therapies are unavailable, the panel recommends bebtelovimab or molnupiravir, in no order of preference.

In ambulatory patients with mild to moderate COVID-19 at high risk for progression to severe disease, IDSA suggests treatment with anti-SARS-CoV-2 mAbs neutralizing antibodies with activity against the predominant regional variants within 7 days of symptom onset rather than no anti-SARS-CoV-2 mAbs. Although bebtelovimab has shown in vitro activity against Omicron sub-variant BA.2, safety and efficacy data are sparse with no comparative data in high-risk patients, limiting use to patients who are not candidates for alternative treatments.

Consult the most recent COVID-19 guidelines available from the NIH [Web] and IDSA [Web] for additional information.

Bebtelovimab Dosage and Administration

General

Pretreatment Screening

• Direct SARS-CoV-2 viral testing.

• Consider local prevalence of SARS-CoV-2 variants prior to initiation of therapy.

Patient Monitoring

• Clinically monitor for infusion-related reactions during administration and observe patient for at least 1 hour after administration is complete.

Dispensing and Administration Precautions

• Completion of FDA MedWatch forms to report all medication errors and all serious adverse events potentially related to bebtelovimab is mandatory. The FDA fact sheet for health care providers that is provided with the drug and available at the FDA website should be consulted for requirements and instructions regarding reporting of adverse reactions and medication errors.

Other General Considerations

• Administer in a setting in which health care 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.

• Administer as soon as possible within 7 days of symptom onset.

• Patients should be advised to continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, wash hands frequently).

Administration

IV Administration

Bebtelovimab must be prepared and administered by a qualified health care provider.

Administer only by IV injection over at least 30 seconds.

Following administration of bebtelovimab, flush extension set with 0.9% sodium chloride to ensure delivery of the entire dose.

Bebtelovimab injection solution is supplied as a single-dose vial. Remove vial from refrigerated storage approximately 20 minutes before preparation. Do not expose the vial to direct heat. Do not shake vial. Bebtelovimab injection solution should each appear as a clear to opalescent and colorless to slightly yellow to slightly brown solution. Discard vial if solution is cloudy, discolored, or visible particles are observed.

Withdraw 2 mL of bebtelovimab injection solution from a vial labeled as containing 175 mg/2 mL (87.5 mg/mL) of bebtelovimab into a disposable syringe.

Administer the prepared dose immediately. If immediate administration is not possible, store the syringe for up to 24 hours at refrigerated temperature (2–8ºC) or up to 7 hours at room temperature (20–25ºC). If the prepared syringe is refrigerated, allow the syringe to equilibrate to room temperature for approximately 20 minutes prior to administration.

Bebtelovimab injection solution contains no preservatives; discard any unused solution remaining in the vial(s).

Rate of Administration

Administer by IV injection over at least 30 seconds.

Dosage

Pediatric Patients

Coronavirus Disease 2019 (COVID-19)

Nonhospitalized patients with Mild to Moderate COVID-19

IV

The FDA EUA that permits use of bebtelovimab for the treatment of coronavirus disease 2019^{† [off-label]} states that pediatric patients ≥12 years of age weighing ≥40 kg should receive 175 mg of bebtelovimab administered as an IV injection. The dose should be administered as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset.

Adults

Coronavirus Disease 2019 (COVID-19)†

Nonhospitalized patients with Mild to Moderate COVID-19

IV

The FDA EUA that permits use of bebtelovimab for the treatment of coronavirus disease 2019^{† [off-label]} states that adults should receive 175 mg of bebtelovimab administered as an IV injection. The dose should be administered as soon as possible after positive results of direct SARS-CoV-2 viral testing and within 7 days of symptom onset.

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment necessary.

Moderate or severe hepatic impairment: Not studied.

Renal Impairment

Dosage adjustment not necessary.

Geriatric Patients

Dosage adjustment not necessary.

Cautions for Bebtelovimab

Contraindications

• EUA states none.

Warnings/Precautions

Hypersensitivity and Injection-related Reactions

Serious hypersensitivity reactions, including anaphylaxis, observed with other SARS-CoV-2 monoclonal antibodies and could occur with administration of bebtelovimab. Hypersensitivity reactions occurring more than 24 hours after administration, reported with SARS-CoV-2-specific monoclonal antibody therapy.

Such reactions may be severe or life-threatening. Signs and symptoms of infusion-related reactions may include fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmias (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, vasovagal reactions (e.g., presyncope, syncope), dizziness, and diaphoresis.

If signs and symptoms of an infusion-related reaction, anaphylaxis or other clinically important hypersensitivity reaction occur, immediately discontinue bebtelovimab and initiate appropriate medications and/or supportive care.

Clinical Worsening after SARS-CoV-2-specific Monoclonal Antibody Administration

Clinical worsening of COVID-19, including signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmias (e.g., atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status, reported after administration of SARS-CoV-2-specific monoclonal antibody therapy; hospitalization required in some cases. It is not known whether these events were related to the SARS-CoV-2-specific monoclonal antibody or occurred because of progression of COVID-19.

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

Not authorized for use under the EUA in patients who are hospitalized due to COVID-19, require oxygen therapy and/or respiratory support due to COVID-19, or are on chronic oxygen therapy and/or respiratory support due to an underlying non-COVID-19-related comorbidity, or require an increase in baseline oxygen flow rate and/or respiratory support due to COVID-19. Benefit of treatment in patients hospitalized due to COVID-19 not studied.

SARS-CoV-2-specific monoclonal antibodies, such as bebtelovimab, may be associated with worse clinical outcomes when administered to hospitalized COVID-19 patients requiring high-flow oxygen or mechanical ventilation.

EUA Requirements for Patient Monitoring and Mandatory FDA MedWatch Reporting

Safety and efficacy of bebtelovimab not established. FDA issued an EUA that permits use of bebtelovimab for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in certain adults and pediatric patients in an appropriate setting via IV injection using the dosage recommended in the EUA.

Only limited data available regarding adverse effects associated with use of bebtelovimab. Serious and unexpected adverse events may occur that have not been previously reported with use of the drug.

Completion of FDA MedWatch forms to report all medication errors and all serious adverse events potentially related to bebtelovimab is mandatory. The FDA fact sheet for health care providers that is provided with the drug and available at the FDA website should be consulted for requirements and instructions regarding reporting of adverse reactions and medication errors.

Specific Populations

Pregnancy

Data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. The estimated background risk of major birth defects and miscarriage related to COVID-19 is unknown.

Infusion-related and severe hypersensitivity reactions have been observed with the administration of bebtelovimab, including in pregnant individuals. Manage appropriately and provide obstetrical care for pregnant individuals who develop hypersensitivity or infusion-related reactions.

Bebtelovimab should be used during pregnancy only if the potential benefit outweighs the potential risk to the mother and fetus. If the drug is used in a pregnant female, no dosage adjustment is necessary.

Lactation

Not known whether bebtelovimab is distributed into human or animal milk or has effects on the breast-fed infant or milk production.

Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for bebtelovimab and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition. Dosage adjustment not necessary if used in a breast-feeding female.

Pediatric Use

The FDA EUA permits use of bebtelovimab for the treatment of mild to moderate COVID-19 in certain pediatric patients ≥12 years of age weighing ≥40 kg).

Bebtelovimab is not authorized for use in pediatric patients <12 years of age or weighing <40 kg. Safety and efficacy of the drug have not been assessed in pediatric patients.

The EUA-recommended dosage of bebtelovimab in patients 12 to <18 years of age weighing ≥40 kg is expected to result in serum exposures of the drug comparable to those observed in adults.

Geriatric Use

Based on population pharmacokinetic analyses of patients 14–89 years of age, there was no impact of age on the pharmacokinetics of bebtelovimab.

Hepatic Impairment

Mild hepatic impairment: Pharmacokinetics of bebtelovimab not substantially affected.

Moderate or severe hepatic impairment: Not studied.

Renal Impairment

Renal impairment not expected to affect pharmacokinetics of bebtelovimab since the drug is not eliminated by renal excretion.

Dialysis is not expected to impact the pharmacokinetics of bebtelovimab.

Common Adverse Effects

Most common adverse reactions are infusion-related reactions (0.3%), pruritus (0.3%), and rash (0.8%).

Drug Interactions

Not metabolized by CYP isoenzymes and not renally excreted; therefore, interactions are unlikely if bebtelovimab is used concomitantly with drugs that are substrates, inducers, or inhibitors of CYP isoenzymes or with drugs that are renally excreted.

Bebtelovimab Pharmacokinetics

Distribution

Not known whether bebtelovimab is distributed into human or animal milk.

Elimination

Metabolism

Not metabolized by CYP isoenzymes.

Elimination Route

Not eliminated by renal excretion.

Dialysis not expected to affect pharmacokinetics.

Half-life

Approximately 11.5 days.

Special Populations

Renal impairment: Not expected to affect bebtelovimab exposure since monoclonal antibodies with molecular mass >69 kDa do not undergo renal elimination.

Mild hepatic impairment: No significant difference in pharmacokinetics compared with patients with normal hepatic function.

Moderate or severe hepatic impairment: Not studied.

Stability

Storage

Parenteral

Injection, solution

Refrigerate (2–8°C); store in original carton to protect from light. Do not freeze, shake, or expose to direct light.

If immediate administration not possible, store prepared syringe for up to 7 hours at room temperature (20–25°C) or for up to 24 hours at refrigerated temperature (2–8°C).

Actions

• Bebtelovimab (IgG_1κ) is a SARS-CoV-2-specific recombinant human monoclonal antibody; produced in a Chinese hamster ovary (CHO) cell line.

• Binds to the spike protein of SARS-CoV-2 and is unmodified in the Fc region.

• Neutralized USA/WA/1/2020 isolate of SARS-CoV-2 with estimated EC₅₀ value of 0.044 nM (6.4 ng/mL).

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

• Potential risk of treatment failure due to development of viral variants resistant to bebtelovimab. Global surveillance is ongoing to evaluate currently circulating SARS-CoV-2 variants for potential resistance to SARS-CoV-2-specific monoclonal antibodies, including bebtelovimab.

• Pseudotyped VLP assessment using full-length spike genes from different variant lineages indicate that bebtelovimab retains activity (<5-fold reduction) against the Alpha (B.1.1.7, UK origin), Beta (B.1.351, South Africa origin), Gamma (P.1, Brazil origin), Delta (B.1.617.2, India origin), Delta [+K417N] (AY.1/AY.2, India origin), Epsilon (B.1.427/B.1.429, California origin), Iota (B.1.526, New York origin), Kappa (B.1.617.1, India origin), Lambda (C.37, Peru origin), Omicron (B.1.1.529/BA.1, South Africa origin), Omicron [+R346K] (BA.1.1), Omicron BA.2, and Omicron BA.2.12.1 (BA.2 full-length spike + L452Q substitution) variant lineages. Bebtelovimab also has been shown to retain activity against Omicron BA.4 and BA.5. The Mu (B.1.621, Colombia origin) variant showed a reduction in susceptibility to bebtelovimab of 5.3-fold.

• Although the clinical impact is not known, it is possible that bebtelovimab resistance-associated variants could have cross-resistance to other SARS-CoV-2-specific monoclonal antibodies that target the receptor binding domain of the virus.

Advice to Patients

• The Fact Sheet for Patients, Parents, and Caregivers: Emergency Use Authorization (EUA) of Bebtelovimab for Coronavirus Disease 2019 (COVID-19) must be provided to patients or parent/caregivers prior to administration of bebtelovimab.

• Inform patients or parent/caregivers that FDA authorized the emergency use of bebtelovimab, which is an investigational drug that has not received FDA approval, for use in certain nonhospitalized adults and pediatric patients with mild to moderate COVID-19 who are at high risk for progressing to severe COVID-19, including hospitalization or death.

• Inform patients or parent/caregivers that they have the option to accept or refuse bebtelovimab.

• Inform pregnant individuals of the risk of hypersensitivity and infusion-related reactions with bebtelovimab as well as the maternal and fetal risk of untreated COVID-19.

• Provide patients or parent/caregivers with information on available alternative treatments and the risks and benefits of those alternatives, including clinical trials.

• Inform patients or parent/caregivers about the significant known and potential risks and benefits of bebtelovimab, and the extent to which such risks and benefits are unknown.

• Importance of immediately reporting any allergic reactions that occur during or after receiving bebtelovimab (e.g., fever, chills, nausea, headache, shortness of breath, low or high blood pressure, rapid or slow heart rate, chest discomfort or pain, weakness, confusion, tiredness, wheezing, rash including urticaria, pruritus, muscle aches, dizziness, sweating, swelling of the lips, face, or throat) to clinicians.

• Advise patients treated with bebtelovimab that they should continue to self-isolate and use infection control measures (e.g., wear mask, isolate, socially distance, avoid sharing personal items, clean and disinfect “high touch” surfaces, wash hands frequently) according to CDC guidelines.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.

• Importance of females informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

FDA issued an emergency use authorization (EUA) for bebtelovimab that allows use of the drug for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in certain nonhospitalized adults and pediatric patients who are at high risk for progression to severe COVID-19, including hospitalization or death. Contact the manufacturer (Eli Lilly and Company) at 1-855-545-5921 for information on how to obtain bebtelovimab for use under the EUA.

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