Identification

Summary

Bebtelovimab is a human IgG1κ monoclonal antibody targeted against the spike protein of SARS-CoV-2 which is used in the treatment of mild-to-moderate COVID-19.

Generic Name
Bebtelovimab
DrugBank Accession Number
DB16755
Background

Bebtelovimab (LY-COV1404, LY-3853113) is a human monoclonal antibody approved for emergency use in the treatment of COVID-19. It binds to a portion of the SARS-CoV-2 spike (S) protein's receptor-binding domain, thereby preventing spike protein interaction with ACE2 and subsequent viral entry into host cells. Bebtelovimab is notable in that the epitope to which it binds appears infrequently mutated, making it a viable candidate for use in resistant SARS-CoV-2 strains (i.e. variants of concern, VOCs), including the B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants.1 This is in contrast to previously developed COVID-19 monoclonal antibody treatments - including bamlanivimab, etesevimab, casirivimab, and imdevimab - which have been found ineffective in the treatment of COVID-19 caused by the Omicron variant.4

Bebtelovimab was issued an emergency use authorization (EUA) by the FDA on February 11, 2022, for the treatment of mild-to-moderate COVID-19 in select patients.3 In November 2022, the FDA updated the Health Care Provider Fact Sheet for bebtelovimab to inform of its expected reduced activity against certain emerging Omicron subvariants of SARS-CoV-2.5

Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
144000.0 Da
Sequences
>Heavy Chain
QITLKESGPTLVKPTQTLTLTCTFSGFSLSISGVGVGWLRQPPGKALEWLALIYWDDDKR
YSPSLKSRLTISKDTSKNQVVLKMTNIDPVDTATYYCAHHSISTIFDHWGQGTLVTVSSA
STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG
LYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGP
SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS
TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ
QGNVFSCSVMHEALHNHYTQKSLSLSPGK
>Light Chain
QSALTQPASVSGSPGQSITISCTATSSDVGDYNYVSWYQQHPGKAPKLMIFEVSDRPSGI
SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTTSSAVFGGGTKLTVLGQPKAAPSVTL
FPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSY
LSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS
References:
  1. KEGG DRUG: Bebtelovimab [Link]
Download FASTA Format
Synonyms
  • Bebtelovimab
External IDs
  • LY-3853113
  • LY-COV1404
  • LY3853113

Pharmacology

Indication

The FDA has issued an emergency use authorization (EUA) for the use of bebtelovimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients (≥12 years old and ≥40 kg) who are positive for SARS-CoV-2 infection, are at a high risk of progression to severe COVID-19, and for whom alternative treatment options are not accessible or clinically appropriate.2

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Associated Conditions
Contraindications & Blackbox Warnings
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Pharmacodynamics

Bebtelovimab binds the SARS-CoV-2 spike protein with a dissocation constant KD = 0.046 - 0.075 nM and blocks spike protein attachment to the human ACE2 receptor with an IC50 value of 0.39 nM.2

Mechanism of action

Bebtelovimab is a neutralizing human IgG1κ monoclonal antibody targeted against the spike (S) protein of SARS-CoV-2,2 which is responsible for facilitating viral entry into host cells. More specifically, bebtelovimab binds to an epitope of the S protein receptor-binding domain (RBD) which overlaps the ACE2-interacting site, effectively inhibiting the interaction between ACE2 and the S protein required for viral entry.1

Of note, the epitope to which bebtelovimab binds is infrequently mutated, making it theoretically less susceptible to viral resistance.1 In vitro studies using a number of variants of concern (VOCs) demonstrated retained activity across all variants tested, including the newer and highly infectious B.1.1.529 (Omicron) variant.1

TargetActionsOrganism
ASpike glycoprotein
antibody
SARS-CoV-2
Absorption

Following a single intravenous dose of 175mg, the mean Cmax and AUCinf of bebtelovimab were 59.8 mcg/mL and 522 mcg.day/mL, respectively.2

Volume of distribution

At steady-state, the volume of distribution of bebtelovimab is 4.61 L.2

Protein binding

Not Available

Metabolism

As with other therapeutic proteins, bebtelovimab is likely degraded via catabolic processes into smaller peptides and amino acids.

Route of elimination

Not Available

Half-life

Following a single intravenous dose of 175mg, the mean elimination half-life of bebtelovimab was 11.5 days.2

Clearance

Following a single intravenous dose of 175mg, the mean clearance of bebtelovimab was 0.335 L/day.2

Adverse Effects
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Toxicity

Single doses of up to 1750mg of bebtelovimab (10 times the authorized dose) have been administered in clinical trials without evidence of dose-limited toxicity. Treatment of bebtelovimab overdose should consist of general supportive measures.2

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Bebtelovimab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Bebtelovimab.
AducanumabThe risk or severity of adverse effects can be increased when Aducanumab is combined with Bebtelovimab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Bebtelovimab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Bebtelovimab.
AmivantamabThe risk or severity of adverse effects can be increased when Amivantamab is combined with Bebtelovimab.
AnifrolumabThe risk or severity of adverse effects can be increased when Anifrolumab is combined with Bebtelovimab.
AnsuvimabThe risk or severity of adverse effects can be increased when Ansuvimab is combined with Bebtelovimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Bebtelovimab.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Bebtelovimab.
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Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BebtelovimabInjection, solution87.5 mg/1mLIntravenousEli Lilly and Company2022-02-11Not applicableUS flag

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
  • Humans

Chemical Identifiers

UNII
8YL4SYR6CU
CAS number
2578319-11-4

References

General References
  1. Westendorf K, Wang L, Zentelis S, Foster D, Vaillancourt P, Wiggin M, Lovett E, van der Lee R, Hendle J, Pustilnik A, Sauder JM, Kraft L, Hwang Y, Siegel RW, Chen J, Heinz BA, Higgs RE, Kallewaard N, Jepson K, Goya R, Smith MA, Collins DW, Pellacani D, Xiang P, de Puyraimond V, Ricicova M, Devorkin L, Pritchard C, O'Neill A, Dalal K, Panwar P, Dhupar H, Garces FA, Cohen C, Dye J, Huie KE, Badger CV, Kobasa D, Audet J, Freitas JJ, Hassanali S, Hughes I, Munoz L, Palma HC, Ramamurthy B, Cross RW, Geisbert TW, Menacherry V, Lokugamage K, Borisevich V, Lanz I, Anderson L, Sipahimalani P, Corbett KS, Yang ES, Zhang Y, Shi W, Zhou T, Choe M, Misasi J, Kwong PD, Sullivan NJ, Graham BS, Fernandez TL, Hansen CL, Falconer E, Mascola JR, Jones BE, Barnhart BC: LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. bioRxiv. 2022 Jan 7. doi: 10.1101/2021.04.30.442182. [Article]
  2. FDA Emergency Use Authorization Fact Sheet: Bebtelovimab injection for intravenous administration [Link]
  3. FDA News Release: FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 that Retains Activity Against Omicron Variant [Link]
  4. FDA News Release: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant [Link]
  5. FDA Drug Safety and Availability: FDA Updates on Bebtelovimab [Link]
RxNav
2592360
Wikipedia
Bebtelovimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedOtherCoronavirus Disease 2019 (COVID‑19)1
2CompletedTreatmentCoronavirus Disease 2019 (COVID‑19)1
2, 3RecruitingTreatmentCoronavirus Disease 2019 (COVID‑19)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionIntravenous87.5 mg/1mL
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

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Kind
Protein
Organism
SARS-CoV-2
Pharmacological action
Yes
Actions
Antibody
General Function
Spike protein S1 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection. Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Can be alternatively processed by host furin (PubMed:32362314). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.
Specific Function
Host cell surface receptor binding
Gene Name
S
Uniprot ID
P0DTC2
Uniprot Name
Spike glycoprotein
Molecular Weight
141177.29 Da
References
  1. FDA Emergency Use Authorization Fact Sheet: Bebtelovimab injection for intravenous administration [Link]

Drug created at February 11, 2022 20:52 / Updated at December 01, 2022 11:30