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Identification
- Summary
Faricimab is an IgG1-derived bispecific antibody against VEGF-A and Ang-2 for the treatment of age-related macular degeneration and diabetic macular edema.
- Brand Names
- Vabysmo
- 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 was approved by the FDA on January 28, 2022, and is currently marketed under the trademark VABYSMO by Genentech, Inc.7 It received subsequent approval for the same indications in Canada in May 2022.8 In July 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended faricimab be granted marketing authorization for the treatment of neovascular age-related macular degeneration and diabetic macular edema.9
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6506H9968N1724O1026S45
- Protein Average Weight
- 149000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Faricimab
- External IDs
- RG-7716
- RG7716
- RO-6867461
- RO6867461
- WHO 10563
Pharmacology
- Indication
Faricimab is indicated for the treatment of neovascular (wet) age-related macular degeneration (nAMD) and diabetic macular edema (DME).7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Diabetic macular edema (dme) •••••••••••• ••••••••• Treatment of Neovascular age-related macular degeneration (namd) •••••••••••• ••••• ••••••••• Treatment of Neovascular age-related macular degeneration (namd) •••••••••••• ••••••••• Treatment of Visual impairment •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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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-2.3,5,6 Faricimab suppresses endothelial proliferation, neovascularization, and vascular permeability, which are associated with the increased retinal thickness observed in nAMD and DME. In four phase 3 studies in nAMD and DME, faricimab reduced central subfield thickness through the first year in all treatment arms.7
As with other medications administered intravitreally, faricimab carries a risk of transient increases in intraocular pressure, endophthalmitis, and retinal detachment. Proper injection techniques should always be observed, and patients monitored carefully following injection. Low risk of arterial thromboembolic events, defined as nonfatal stroke or myocardial infarction and vascular death, has been documented with faricimab.7
- 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
Target Actions Organism AVascular endothelial growth factor A, long form antagonistHumans AAngiopoietin-2 antagonistHumans - Absorption
Faricimab unbound plasma Cmax are estimated to be 0.23 ± 0.07 and 0.22 ± 0.07 μg/mL in nAMD and DME patients, respectively; these plasma levels are achieved approximately two days post-dose (Tmax). Following repeated intravitreal administration on a q8w schedule, mean plasma trough free faricimab concentrations are predicted to be 0.002-0.003 μg/mL. No accumulation is expected in either the vitreal fluid or plasma.7
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
Faricimab metabolism has not been fully characterized; as an antibody, faricimab is expected to be catabolized like endogenous immunoglobulins.7
- Route of elimination
Faricimab elimination has not been fully characterized; faricimab may be excreted renally following its breakdown into smaller peptides and amino acids through cellular catabolism.7
- Half-life
Faricimab has an estimated mean apparent systemic half-life of 7.5 days.7
- Clearance
Not Available
- Adverse Effects
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Toxicity information regarding faricimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as conjunctival hemorrhage. Symptomatic and supportive measures are recommended. Due to its mechanism of action, faricimab may pose a risk to reproductive capacity.7
- 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
- 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 Vabysmo Solution 6 mg / 0.05 mL Intravitreal Hoffmann La Roche 2022-07-18 Not applicable Canada 
Vabysmo Injection, solution 6 mg/0.05mL Intravitreal Genentech, Inc. 2022-01-28 Not applicable US 
Vabysmo Injection, solution 120 mg/ml Intravitreal Roche Registration Gmb H 2023-02-08 Not applicable EU 
Categories
- ATC Codes
- S01LA09 — Faricimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineovascularisation Agents
- Blood Proteins
- Globulins
- Growth Inhibitors
- Growth Substances
- Immunoglobulins
- Immunoproteins
- Ocular Vascular Disorder Agents
- Ophthalmologicals
- Proteins
- Sensory Organs
- 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
- QC4F7FKK7I
- CAS number
- 1607793-29-2
References
- Synthesis Reference
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.
- General References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- FDA Approved Drug Products: VABYSMO (faricimab-svoa) injection [Link]
- Health Canada Product Monograph: Vabysmo (faricimab) solution for intravitreal injection [Link]
- EMA CHMP Positive Opinion: Vabysmo (faricimab) [Link]
- EMA Approved Drug Products: Vabysmo (faricimab) solution of intravitreal injection [Link]
- External Links
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 Recruiting Not Available Diabetic Macular Edema (DME) / Neovascular Age-Related Macular Degeneration (nAMD) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Diabetic Macular Edema (DME) / Neovascular Age-Related Macular Degeneration (nAMD) / Retinal Vein Occlusion 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Neovascular Age-Related Macular Degeneration (nAMD) 1 somestatus stop reason just information to hide 4 Enrolling by Invitation Supportive Care Diabetic Retinopathy (DR) / Vitreous Hemorrhage Due to Diabetes Mellitus 1 somestatus stop reason just information to hide 4 Not Yet Recruiting Treatment Diabetic Macular Edema (DME) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravitreal 120 mg/ml Injection, solution Intravitreal 6 mg/0.05mL Solution Intraocular 6.00 mg Solution Intravitreal 6 mg / 0.05 mL Solution Intravitreal 6 mg/0.05mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Participates in the induction of key genes involved in the response to hypoxia and in the induction of angiogenesis such as HIF1A (PubMed:35455969). Involved in protecting cells from hypoxia-mediated cell death (By similarity)
- Specific Function
- Chemoattractant activity
- Gene Name
- VEGFA
- Uniprot ID
- P15692
- Uniprot Name
- Vascular endothelial growth factor A, long form
- Molecular Weight
- 43596.94 Da
References
- 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. [Article]
- 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 (PubMed:15284220, PubMed:19116766, PubMed:19223473, PubMed:9204896). Can induce tyrosine phosphorylation of TEK/TIE2 in the absence of ANGPT1 (PubMed:15284220, PubMed:19116766, PubMed:19223473, PubMed:9204896). 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 (PubMed:15284220, PubMed:19116766, PubMed:19223473, PubMed:9204896). Involved in the regulation of lymphangiogenesis (PubMed:32908006)
- Specific Function
- Metal ion binding
- Gene Name
- ANGPT2
- Uniprot ID
- O15123
- Uniprot Name
- Angiopoietin-2
- Molecular Weight
- 56918.885 Da
References
- 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. [Article]
Drug created at May 20, 2019 15:10 / Updated at December 01, 2022 11:29