bebtelovimab (Investigational)

EUA requirement

Completion of FDA MedWatch Form to report all medication errors and serious adverse events is mandatory

<1%

Rash (0.8%)

Infusion-related reactions (0.3%)

Pruritus (0.3%)

Contraindications

None

Cautions

Hypersensitivity

• Serious hypersensitivity reaction, including anaphylaxis, observed with other COVID-19 mAbs, and may occur with bebtelovimab
• Hypersensitivity reactions occurring >24 hr after infusion observed with bebtelovimab when administered with other mAbs
• Infusion-related reactions may be severe or life-threatening
• If signs and symptoms occur, immediately discontinue IV infusion, and initiate appropriate medications and/or supportive care
• Infusion-related reactions reported, including fever, difficulty breathing, reduced oxygen saturation, chills, fatigue, arrhythmia (eg, 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, dizziness, and diaphoresis
• Administer appropriate medication/supportive care if infusion-related reactions occurs

Clinical worsening after administration

• Clinical worsening of COVID-19 after administration reported; signs or symptoms may include fever, hypoxia or increased respiratory difficulty, arrhythmia (eg, atrial fibrillation, sinus tachycardia, bradycardia), fatigue, and altered mental status
• Some of these events required hospitalization
• Unknown if these events were related to mAbs or were due to progression of COVID-19

Severe COVID-19

• Treatment benefit not observed in patients hospitalized with COVID-19
• Monoclonal antibodies may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation

• Therefore, not authorized for use in patients

  • Who are hospitalized with COVID-19, OR
  • Who require oxygen therapy for COVID-19, OR
  • Who require an increase in baseline oxygen flow rate because of COVID-19 (in those on long-term oxygen therapy for underlying non-COVID-19–related comorbidity)

Viral variants

• Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies
• Prescribing clinicians should consider prevalence of resistant variants in their area
• Health care providers should review antiviral resistance information provided by state and local health departments
• November 4, 2022: Expected reduced activity against Omicron subvariants BQ.1 and BQ.1.1 (fold reduction in susceptibility >672); prescribers should monitor regional variant frequency data to determine if using bebtelovimab remains effective
• Variant proportions circulating in the US can be monitored at the CDC website

Drug interaction overview

• Not renally excreted or metabolized by CYP450 enzymes
• Interactions with concomitant renally excreted drugs or drugs that are CYP450 substrates, inducers, or inhibitors are unlikely

Pregnancy

Data are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Use during pregnancy if potential benefit outweighs potential risk for mother and fetus

Pregnant females are considered a high-risk population for severe COVID-19

Clinical considerations

• COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death

Lactation

Data are unavailable on presence in human or animal milk, effects on breastfed infants, or effects on milk production

Maternal IgG is known to be present in human milk

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for bebtelovimab and any potential adverse effects on breastfed child from bebtelovimab or from underlying maternal condition

Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant neutralizing human IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2 and is unmodified in the Fc region; maintains binding and neutralizing activity across currently known and reported variants of concern, including Omicron and BA.2

Absorption

Peak plasma concentration: 59.8 mcg/mL

Peak plasma concentration (day 29): 4.35 mcg/mL

AUC: 522 mcg⋅day/mL

Distribution

Vd: 4.61 L

Metabolism

Expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as other IgG mAbs

Elimination

Half-life: 11.5 days

Clearance: 0.335 L/day

IV Preparation

Remove vial from refrigerator and allow to equilibrate to room temperature for ~20 minutes; do not expose to direct heat

Do not shake vial

Inspect vial visually for particulate matter and discoloration; solution is clear to opalescent and colorless to slightly yellow to slightly brown; discard if cloudy, discolored, or visible particles observed

Withdraw 2 mL (175 mg) from vial into disposable syringe; discard any product remaining in vial

Product is preservative-free, therefore, should be administer immediately; if immediate administration not possible, may refrigerate (up to 24 hr) or at room temperature (up to 7 hr)

Collect supplies for administration

• 1 disposable polypropylene dosing syringe capable of holding 2 mL
• Syringe extension set: Polycarbonate and polyvinylchloride without di-ethylhexylphthalate (DEHP)
• 0.9% NaCl to flush tubing

IV Administration

To be prepared by qualified healthcare professional

Attach and prime syringe extension set, administer dose IV over at least 30 seconds

Flush extension set with 0.9% NaCl to ensure delivery of required dose

May only be administered in settings with immediate access to medications to treat a severe infusion reaction (eg, anaphylaxis) and ability to activate emergency medical system, as necessary

Monitor patients for possible infusion-related reactions during administration and observe for at least 1 hr after injection

Storage

Unopened vials

• Preservative-free
• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
• Do not freeze, shake, or expose to direct light

Prepared syringe

• Refrigerated at 2-8ºC (36-46ºF) for up to 24 hr, OR
• Room temperature at 20-25ºC (68-7ºF) for up to 7 hr
• If refrigerated, allow prepared syringe to equilibrate to room temperature for ~20 minutes before administration