Bebtelovimab
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certain emerging Omicron subvariants of SARS-CoV-2.5 On November 30, 2022, the EUA for bebtelovimab was officially withdrawn due to a lack of efficacy against Omicron subvariants, therefore bebtelovimab is no longer authorized for emergency use in the US.6
- Type
- Biotech
- Groups
- Investigational, Withdrawn
- 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
Download FASTA FormatReferences:
- KEGG DRUG: Bebtelovimab [Link]
- Synonyms
- Bebtelovimab
- External IDs
- LY-3853113
- LY-COV1404
- LY3853113
Pharmacology
- Indication
Bebtelovimab currently has no approved indications.
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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
Target Actions Organism ASpike glycoprotein antibodySARS-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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Bebtelovimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Bebtelovimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Bebtelovimab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Bebtelovimab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Bebtelovimab. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bebtelovimab Injection, solution 87.5 mg/1mL Intravenous Eli Lilly and Company 2022-02-11 2024-08-28 US
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
- 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]
- FDA Emergency Use Authorization Fact Sheet: Bebtelovimab injection for intravenous administration [Link]
- FDA News Release: FDA Authorizes New Monoclonal Antibody for Treatment of COVID-19 that Retains Activity Against Omicron Variant [Link]
- FDA News Release: FDA Limits Use of Certain Monoclonal Antibodies to Treat COVID-19 Due to the Omicron Variant [Link]
- FDA Drug Safety and Availability: FDA Updates on Bebtelovimab [Link]
- FDA Drug Safety and Availability: FDA Announces Bebtelovimab is Not Currently Authorized in Any US Region [Link]
- External Links
- 2592360
- Wikipedia
- Bebtelovimab
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Terminated Other Coronavirus Disease 2019 (COVID‑19) 1 2 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1 2, 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous 87.5 mg/1mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- 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
- FDA Emergency Use Authorization Fact Sheet: Bebtelovimab injection for intravenous administration [Link]
Drug created at February 11, 2022 20:52 / Updated at December 08, 2022 21:18