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Identification
- Summary
Cilgavimab is an extended half-life recombinant monoclonal IgG1κ antibody directed against the SARS-CoV-2 S protein for COVID-19 prophylaxis in individuals unable to undergo COVID-19 immunization.
- Generic Name
- Cilgavimab
- DrugBank Accession Number
- DB16393
- Background
SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Blocking the interaction between the receptor-binding domain (RBD) of the S1 subunit and ACE2 inhibits viral host cell entry; animal studies indicate that antibodies capable of blocking this interaction reduce viral load and improve clinical symptoms of infection.2,3 Cilgavimab (formerly AZD1061) is a recombinant monoclonal antibody produced in Chinese hamster ovary (CHO) cells derived from a neutralizing antibody isolated from a patient with a natural history of SARS-CoV-2 infection and modified through targeted amino acid substitutions to exhibit an extended (~85-day) half-life.1,2,4 As the RBD binding site of cilgavimab does not overlap with that of tixagevimab, the two can be administered to synergistically impair SARS-CoV-2 infection in individuals who may be exposed to the virus.1,3,4
Cilgavimab is not approved for any indication by the FDA. Cilgavimab, in combination with tixagevimab, was issued an FDA emergency use authorization (EUA) on December 9, 2021, for the pre-exposure prophylaxis of COVID-19 in individuals at increased risk for whom vaccination is not recommended. The combination is co-packaged and available under the name EVUSHELD (formerly AZD7442).4 EVUSHELD was granted marketing authorization by the EMA on March 28, 2022,5 and was approved in Canada soon after, on April 14, 2022.7
In October 2022, the FDA and Health Canada released safety alerts regarding the risk of developing COVID-19 when exposed to SARS-CoV-2 variants not neutralized by EVUSHELD. Certain SARS-CoV-2 Omicron subvariants may be associated with resistance to monoclonal antibodies, such as EVUSHELD. The FDA and Health Canada advise healthcare providers to inform patients of this risk.8,9
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6626H10218N1750O2078S44
- Protein Average Weight
- 152000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Cilgavimab
- External IDs
- AZD-1061
- AZD1061
Pharmacology
- Indication
Cilgavimab has been issued an emergency use authorization (EUA) by the FDA, in combination with tixagevimab, for the pre-exposure prophylaxis of COVID-19 in adult and pediatric patients aged 12 years and older weighing at least 40 kg. Furthermore, patients must not be currently infected with SARS-CoV-2 or have had known exposure to an individual infected with SARS-CoV-2 and must either be immunocompromised due to a medical condition, medication, or treatment or be otherwise ineligible for vaccination with any eligible COVID-19 vaccine due to a history of severe adverse reactions.4
In the US, the combination of cilgavimab and tixagevimab is not authorized for the treatment or post-exposure prophylaxis of COVID-19 and is not a substitute for COVID-19 vaccination. Individuals receiving therapy following COVID-19 vaccination should wait at least two weeks.4
In Europe and Canada, cilgavimab in combination with tixagevimab is an approved pre-exposure prophylaxis therapy for COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg.6,7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination for prophylaxis of Coronavirus disease 2019 (covid‑19) Combination Product in combination with: Tixagevimab (DB16394) •••••••••••• ••••••••••• ••••• •••••• •• •• •• •••• ••••••••• Used in combination for prophylaxis of Coronavirus disease 2019 (covid‑19) Combination Product in combination with: Tixagevimab (DB16394) •••••••••••• •••••• ••••••••• •••••• •• •• •• ••••• •••••••••• ••• •••••••• ••••••••••• ••••••••• Used in combination for prophylaxis of Coronavirus disease 2019 (covid‑19) Combination Product in combination with: Tixagevimab (DB16394) •••••••••••• •••••• ••••••••• ••••••••• •••••• •••••••••••••••••• ••• ••• ••••• •• •••••••• •••••• •••••••• •• •••••••• •••••••••••• •••••• •• •• •• •••• ••••••••• Used in combination to treat Coronavirus disease 2019 (covid‑19) Combination Product in combination with: Tixagevimab (DB16394) •••••••••••• ••••••••••• ••••• ••••••••• •••• •• ••••••••••• •• •••••• ••••••••• •••••• •• •• •• •••• ••••••••• - Associated Therapies
- Contraindications & Blackbox Warnings
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Cilgavimab is an extended half-life recombinant human IgG1κ monoclonal antibody directed against the SARS-CoV-2 spike (S) protein. Administered concurrently with tixagevimab, the combination carries a risk of hypersensitivity reactions and requires caution when administering to patients with thrombocytopenia or a coagulation disorder. Based on limited clinical experience, caution should also be exercised in patients with cardiac risk factors or a history of cardiovascular disease. As there is limited experience with this combination, unexpected serious adverse events may occur.4
- Mechanism of action
SARS-CoV-2, the causative agent of COVID-19, enters cells via the interaction between the trimeric spike (S) glycoprotein and host cell angiotensin-converting enzyme 2 (ACE2). Of the two subunits comprising the trimeric S glycoprotein, the S1 subunit binds ACE2 via its receptor-binding domain (RBD) while the central S2 subunit mediates fusion following S1 shedding.1,2 Large-scale screens suggest that the most potently neutralizing antibodies recovered from the B cells of those convalescing following natural infection with SARS-CoV-2 bind to the RBD of S1 and are capable of disrupting the interaction between the RBD and human ACE2.2
Cilgavimab (AZD1061) is a recombinant human IgG1κ monoclonal antibody based on a neutralizing antibody (COV2-2130) isolated from patients with a natural history of SARS-CoV-2 infection and modified through specific amino acid substitutions to extend its half-life and reduce antibody effector functions.4 Cilgavimab binds to a non-overlapping region of the S1 RBD as tixagevimab and is capable of binding the S protein in both "up" and "down" conformations with a KD of 13.0 pM.2,3,4 Cell culture studies suggest little to no antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), or antibody-dependent natural killer cell activation (ADNKA), suggesting the protective effect is due solely to inhibition of the RBD-ACE2 interaction. Cilgavmiab inhibits RBD-ACE2 binding with an IC50 of 0.53 nM (80 ng/mL) and neutralizes SARS-CoV-2 (strain USA-WA1/2020) in a cellular assay with an EC50 value of 211.5 pM (32 ng/mL).4
As with other antiviral treatments, there is a risk of resistant variants emerging during treatment. Experiments to identify escape variants during culture of recombinant vesicular stomatitis virus expressing the S protein (VSV-SARS-CoV-2) or authentic SARS-CoV-2 (strain USA-WA1/2020) identified K444E, K444R, and R346I as potential single-nucleotide escape variants for cilgavimab (conferring a >200-fold reduction in susceptibility). However, no escape variants were identified to tixagevimab or the combination of cilgavimab and tixagevimab.3,4
Target Actions Organism ASpike glycoprotein binderSARS-CoV-2 - Absorption
A single 150 mg intramuscular dose of cilgavimab, given concurrently with 150 mg of tixagevimab, resulted in a Cmax geometric mean (%CV) of 15.3 (38.5) μg/mL in a median Tmax of 14.0 (range 3.1-60) days. The observed geometric mean (%CV) one, 150, or 210 days following dosing was 3.9 (94.4), 5.5 (35.2), and 3.9 (37.1) μg/mL. This single dose resulted in an AUC0-∞ of 2133 (31.7) μg*day/mL.4
- Volume of distribution
Cilgavimab has an apparent volume of distribution of 8.7 ± 2.73 L.4
- Protein binding
Not Available
- Metabolism
As a monoclonal antibody, cilgavimab is expected to undergo proteolytic degradation.4
- Route of elimination
Cilgavimab is unlikely to undergo renal excretion.4
- Half-life
Cilgavimab has a half-life of 82.9 ± 12.3 days.4
- Clearance
Cilgavimab has an apparent clearance of 0.074 ± 0.028 L/day.4
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Toxicity information regarding cilgavimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects. Symptomatic and supportive measures are recommended.4
- 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 Cilgavimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Cilgavimab. Adenovirus type 7 vaccine live The therapeutic efficacy of Adenovirus type 7 vaccine live can be decreased when used in combination with Cilgavimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Cilgavimab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Cilgavimab. - 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.- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Evusheld Cilgavimab (100 mg/ml) + Tixagevimab (100 mg/ml) Injection, solution Intramuscular Astra Zeneca Ab 2022-05-04 Not applicable EU 
Evusheld Cilgavimab (150 mg / 1.5 mL) + Tixagevimab (150 mg / 1.5 mL) Solution Intramuscular Astra Zeneca 2022-04-19 2024-03-27 Canada 
Categories
- ATC Codes
- J06BD03 — Tixagevimab and cilgavimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antiinfectives for Systemic Use
- Antiviral Agents
- Antiviral monoclonal antibodies
- Antivirals for Systemic Use
- Blood Proteins
- Experimental Unapproved Treatments for COVID-19
- Globulins
- Immune Sera and Immunoglobulins
- Immunoglobulins
- Immunoproteins
- Proteins
- Serum Globulins
- 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 and other mammals
Chemical Identifiers
- UNII
- 1KUR4BN70F
- CAS number
- 2420563-99-9
References
- General References
- Zost SJ, Gilchuk P, Chen RE, Case JB, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Chen EC, Binshtein E, Shrihari S, Ostrowski M, Chu HY, Didier JE, MacRenaris KW, Jones T, Day S, Myers L, Eun-Hyung Lee F, Nguyen DC, Sanz I, Martinez DR, Rothlauf PW, Bloyet LM, Whelan SPJ, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr: Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat Med. 2020 Sep;26(9):1422-1427. doi: 10.1038/s41591-020-0998-x. Epub 2020 Jul 10. [Article]
- Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schafer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr: Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 2020 Aug;584(7821):443-449. doi: 10.1038/s41586-020-2548-6. Epub 2020 Jul 15. [Article]
- Dong J, Zost SJ, Greaney AJ, Starr TN, Dingens AS, Chen EC, Chen RE, Case JB, Sutton RE, Gilchuk P, Rodriguez J, Armstrong E, Gainza C, Nargi RS, Binshtein E, Xie X, Zhang X, Shi PY, Logue J, Weston S, McGrath ME, Frieman MB, Brady T, Tuffy KM, Bright H, Loo YM, McTamney PM, Esser MT, Carnahan RH, Diamond MS, Bloom JD, Crowe JE Jr: Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol. 2021 Oct;6(10):1233-1244. doi: 10.1038/s41564-021-00972-2. Epub 2021 Sep 21. [Article]
- FDA EUA Fact Sheet: EVUSHELD (tixagevimab and cilgavimab) injection [Link]
- Astrazeneca Press Release: Evusheld long-acting antibody combination approved in the EU for pre-exposure prophylaxis (prevention) of COVID-19 in a broad population [Link]
- EMA Approved Drug Products: Evusheld (tixagevimab, cilgavimab) Intramuscular Injection [Link]
- Health Canada Approved Drug Products: EVUSHELD (tixagevimab and cilgavimab) intramuscular injection [Link]
- US Food & Drug Administration: FDA releases important information about risk of COVID-19 due to certain variants not neutralized by Evusheld [Link]
- Health Canada: EVUSHELD (tixagevimab and cilgavimab for injection) - Risk of Prophylaxis or Treatment Failure due to Antiviral Resistance [Link]
- External Links
- 2587306
- Wikipedia
- Tixagevimab/cilgavimab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) 2 somestatus stop reason just information to hide Not Available Completed Not Available Coronavirus Disease 2019 (COVID‑19) / Immunodeficiencies 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Coronavirus Disease 2019 (COVID‑19) / Infections, Coronavirus 1 somestatus stop reason just information to hide 3 Completed Prevention Coronavirus Disease 2019 (COVID‑19) 2 somestatus stop reason just information to hide 3 Completed Treatment Coronavirus Disease 2019 (COVID‑19) 4 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intramuscular Injection, solution; kit Intramuscular; Intravenous Solution Intramuscular - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- SARS-CoV-2
- Pharmacological action
- Yes
- Actions
- Binder
- Curator comments
- Cilgavimab binds to the RBD of the S1 subunit and inhibits interaction of the S protein with human ACE2.
- 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
- Zost SJ, Gilchuk P, Chen RE, Case JB, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Chen EC, Binshtein E, Shrihari S, Ostrowski M, Chu HY, Didier JE, MacRenaris KW, Jones T, Day S, Myers L, Eun-Hyung Lee F, Nguyen DC, Sanz I, Martinez DR, Rothlauf PW, Bloyet LM, Whelan SPJ, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr: Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein. Nat Med. 2020 Sep;26(9):1422-1427. doi: 10.1038/s41591-020-0998-x. Epub 2020 Jul 10. [Article]
- Zost SJ, Gilchuk P, Case JB, Binshtein E, Chen RE, Nkolola JP, Schafer A, Reidy JX, Trivette A, Nargi RS, Sutton RE, Suryadevara N, Martinez DR, Williamson LE, Chen EC, Jones T, Day S, Myers L, Hassan AO, Kafai NM, Winkler ES, Fox JM, Shrihari S, Mueller BK, Meiler J, Chandrashekar A, Mercado NB, Steinhardt JJ, Ren K, Loo YM, Kallewaard NL, McCune BT, Keeler SP, Holtzman MJ, Barouch DH, Gralinski LE, Baric RS, Thackray LB, Diamond MS, Carnahan RH, Crowe JE Jr: Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature. 2020 Aug;584(7821):443-449. doi: 10.1038/s41586-020-2548-6. Epub 2020 Jul 15. [Article]
- Dong J, Zost SJ, Greaney AJ, Starr TN, Dingens AS, Chen EC, Chen RE, Case JB, Sutton RE, Gilchuk P, Rodriguez J, Armstrong E, Gainza C, Nargi RS, Binshtein E, Xie X, Zhang X, Shi PY, Logue J, Weston S, McGrath ME, Frieman MB, Brady T, Tuffy KM, Bright H, Loo YM, McTamney PM, Esser MT, Carnahan RH, Diamond MS, Bloom JD, Crowe JE Jr: Genetic and structural basis for SARS-CoV-2 variant neutralization by a two-antibody cocktail. Nat Microbiol. 2021 Oct;6(10):1233-1244. doi: 10.1038/s41564-021-00972-2. Epub 2021 Sep 21. [Article]
- FDA EUA Fact Sheet: EVUSHELD (tixagevimab and cilgavimab) injection [Link]
Drug created at December 23, 2020 15:59 / Updated at December 01, 2022 11:30