Faricimab

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Summary

Faricimab is an IgG1-derived bispecific antibody against VEGF-A and Ang-2 for the treatment of retinal vascular diseases such as diabetic macular edema, age-related macular degeneration, and retinal vein occlusion.

Generic Name
Faricimab
DrugBank Accession Number
DB15303
Background

Retinal vascular diseases (RVDs) such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO) are typically caused by retinal ischemia and subsequent neovascularization (NV).1,2,3 Vascular endothelial growth factor A (VEGF-A) is a well-known mediator of retinal NV, and many currently approved RVD therapies such as aflibercept and ranibizumab solely target VEGF-A. However, another set of factors, the Tie/Ang axis, comprising the transmembrane Tie-2 receptor and its soluble ligands Ang-1 and Ang-2, has been shown to play critical roles in mediating VEGF-A-induced NV.1,2,3 Faricimab is an IgG1-derived bispecific antibody capable of simultaneously binding to and depleting VEGF-A and Ang-2, which has been developed to improve therapeutic efficacy, especially in patients that respond poorly to anti-VEGF-A monotherapy.1,2,3,4,5,6

Faricimab is under investigation in clinical trial NCT03823287 (A Study to Evaluate the Efficacy and Safety of Faricimab in Participants With Neovascular Age-Related Macular Degeneration (TENAYA)).

Type
Biotech
Groups
Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Chemical Formula
Not Available
Protein Average Weight
Not Available
Sequences
Not Available
Synonyms
  • Faricimab
External IDs
  • RG-7716
  • RG7716
  • RO-6867461
  • RO6867461
  • WHO 10563

Pharmacology

Indication

Not Available

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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Pharmacodynamics

Not Available

Mechanism of action

The retina is largely avascular to facilitate effective photoreceptor function; rather, the retina is fed by both retinal and choroidal capillary networks, pathologies of which result in retinal and choroidal vascular diseases such as diabetic macular edema (DME), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).1,2,3 One of the underlying causes of retinal vascular diseases (RVDs) is retinal neovascularization (NV), the aberrant growth of new vasculature, usually due to sustained retinal ischemia and mediated primarily by vascular endothelial growth factor A (VEGF-A).1,2,3 VEGF-A is a VEGF family member, which also includes VEGF-B, -C, and -D, whose members signal through the VEGF receptors (VEGFRs) VEGFR-1, -2, and -3 to mediate endothelial and lymphatic growth.2 Extensive work in animal models of RVD has demonstrated that VEGF-A is necessary but not sufficient in many cases to mediate NV, suggesting that additional factors may be required in deep retinal capillary beds.1 One such factor has been identified as the angiopoietins Ang-1 and Ang-2 and their cellular receptor Tie-2; Ang-1 is a full Tie-2 agonist whose binding results in Tie-2 phosphorylation and downstream signalling, whereas Ang-2 is a Tie-2 partial agonist/antagonist that inhibits Tie-2 phosphorylation. Ang-1 generally has a protective effect, making endothelial cells less responsive to VEGF-A, while Ang-2 increases VEGF-A-dependent NV and stimulates pericyte apoptosis and breakdown of both the blood-brain and blood-retinal barriers; Ang-2 is upregulated in retinal vascular development and retinal ischemia.1,2,3,4

Faricimab is a bispecific antibody (bsAb) based on human IgG1 comprising two different heavy and two different light chains capable of simultaneously binding to both VEGF-A and Ang-2 produced using the "CrossMab" platform.3,5,6 Faricimab binds VEGF-A and Ang-2 with binding affinities (KD) of approximately 3 and 22 nM, respectively; importantly, faricimab does not detectably bind Ang-1.3 Also, the faricimab Fc region has been modified to reduce binding to FcγR and FcRn receptors. The former virtually eliminates immune-mediated functions such as antibody- and complement-dependent cytotoxicity and antibody-dependent phagocytosis, whereas the latter increases faricimab systemic clearance by reducing FcRn-mediated IgG recycling.3 Thus, faricimab works by depleting both VEGF-A and Ang-2 to prevent retinal NV in the privileged ophthalmic environment.3

TargetActionsOrganism
AVascular endothelial growth factor A
antagonist
Humans
AAngiopoietin-2
antagonist
Humans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Medicalerrors
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Toxicity

Not Available

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.
Not Available
Food Interactions
Not Available

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
Not Available

Chemical Identifiers

UNII
QC4F7FKK7I
CAS number
1607793-29-2

References

General References
  1. Campochiaro PA: Molecular pathogenesis of retinal and choroidal vascular diseases. Prog Retin Eye Res. 2015 Nov;49:67-81. doi: 10.1016/j.preteyeres.2015.06.002. Epub 2015 Jun 23. [PubMed:26113211]
  2. Khan M, Aziz AA, Shafi NA, Abbas T, Khanani AM: Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab. Cells. 2020 Aug 10;9(8). pii: cells9081869. doi: 10.3390/cells9081869. [PubMed:32785136]
  3. Regula JT, Lundh von Leithner P, Foxton R, Barathi VA, Cheung CM, Bo Tun SB, Wey YS, Iwata D, Dostalek M, Moelleken J, Stubenrauch KG, Nogoceke E, Widmer G, Strassburger P, Koss MJ, Klein C, Shima DT, Hartmann G: Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med. 2016 Nov 2;8(11):1265-1288. doi: 10.15252/emmm.201505889. Print 2016 Nov. [PubMed:27742718]
  4. Sharma A, Kumar N, Kuppermann BD, Bandello F, Loewenstein A: Faricimab: expanding horizon beyond VEGF. Eye (Lond). 2020 May;34(5):802-804. doi: 10.1038/s41433-019-0670-1. Epub 2019 Nov 6. [PubMed:31695160]
  5. Schaefer W, Regula JT, Bahner M, Schanzer J, Croasdale R, Durr H, Gassner C, Georges G, Kettenberger H, Imhof-Jung S, Schwaiger M, Stubenrauch KG, Sustmann C, Thomas M, Scheuer W, Klein C: Immunoglobulin domain crossover as a generic approach for the production of bispecific IgG antibodies. Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):11187-92. doi: 10.1073/pnas.1019002108. Epub 2011 Jun 20. [PubMed:21690412]
  6. Labrijn AF, Janmaat ML, Reichert JM, Parren PWHI: Bispecific antibodies: a mechanistic review of the pipeline. Nat Rev Drug Discov. 2019 Aug;18(8):585-608. doi: 10.1038/s41573-019-0028-1. [PubMed:31175342]
Wikipedia
Faricimab

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentDiabetic Macular Edema (DME)1
3Active Not RecruitingTreatmentWet Macular Degeneration1
3Enrolling by InvitationTreatmentDiabetic Macular Edema (DME)1
3Enrolling by InvitationTreatmentWet Macular Degeneration1
3Not Yet RecruitingTreatmentNeovascular Age-Related Macular Degeneration1
3RecruitingTreatmentBranch Retinal Vein Occlusion / Macular Edema1
3RecruitingTreatmentCentral Retinal Vein Occlusion (CRVO) / Hemiretinal Vein Occlusion / Macular Edema1
3RecruitingTreatmentDiabetic Macular Edema (DME)1
2CompletedTreatmentDiabetic Macular Edema (DME)1
2CompletedTreatmentMacular Degeneration, Age-Related / Subfoveal Choroidal Neovascularization1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Not Available
Experimental Properties
Not Available

Targets

Drugtargets
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Vascular endothelial growth factor receptor binding
Specific Function
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of...
Gene Name
VEGFA
Uniprot ID
P15692
Uniprot Name
Vascular endothelial growth factor A
Molecular Weight
27042.205 Da
References
  1. Regula JT, Lundh von Leithner P, Foxton R, Barathi VA, Cheung CM, Bo Tun SB, Wey YS, Iwata D, Dostalek M, Moelleken J, Stubenrauch KG, Nogoceke E, Widmer G, Strassburger P, Koss MJ, Klein C, Shima DT, Hartmann G: Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med. 2016 Nov 2;8(11):1265-1288. doi: 10.15252/emmm.201505889. Print 2016 Nov. [PubMed:27742718]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Antagonist
General Function
Binds to TEK/TIE2, competing for the ANGPT1 binding site, and modulating ANGPT1 signaling. Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1. In the absence of angiogenic inducers, such as VEGF, ANGPT2-mediated loosening of cell-matrix contacts may induce endothelial cell apoptosis with consequent vascular regression. In concert with VEGF, it may facilitate endothelial cell migration and proliferation, thus serving as a permissive angiogenic signal.
Specific Function
Metal ion binding
Gene Name
ANGPT2
Uniprot ID
O15123
Uniprot Name
Angiopoietin-2
Molecular Weight
56918.885 Da
References
  1. Regula JT, Lundh von Leithner P, Foxton R, Barathi VA, Cheung CM, Bo Tun SB, Wey YS, Iwata D, Dostalek M, Moelleken J, Stubenrauch KG, Nogoceke E, Widmer G, Strassburger P, Koss MJ, Klein C, Shima DT, Hartmann G: Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases. EMBO Mol Med. 2016 Nov 2;8(11):1265-1288. doi: 10.15252/emmm.201505889. Print 2016 Nov. [PubMed:27742718]

Drug created on May 20, 2019 15:10 / Updated on February 21, 2021 18:55