Ranibizumab

Identification

Summary

Ranibizumab is a recombinant humanized monoclonal antibody and VEGF-A antagonist used for the management of macular edema after retinal vein occlusion, age-related macular degeneration (wet), and diabetic macular edema.

Brand Names

Byooviz, Cimerli, Lucentis, Susvimo

Generic Name

Ranibizumab

DrugBank Accession Number

DB01270

Background

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody fragment directed against human vascular endothelial growth factor A (VEGF-A), which is a glycoprotein implicated in the pathophysiology of age-related macular degeneration.^2,7 Ranibizumab is used to treat various ocular disorders with abnormal growth of blood vessels, such as neovascular (wet) age-related macular degeneration. The development of ranibizumab first began after bevacizumab, another anti-VEGF anticancer drug, was discovered to inhibit neovascularization and used in the off-label treatment of neovascular age-related macular degeneration for intravenous injection. In order to improve drug delivery to the target organ, ranibizumab is available for intravitreal use.³

Ranibizumab was initially approved by the FDA in 2006 ² and by the European Commission (EC) in 2007.¹⁰ It is marketed under the brand names LUCENTIS and SUSVIMO. BYOOVIZ, a biosimilar of LUCENTIS, was approved by Health Canada in March 2022, making it the first and only biosimilar drug of ranibizumab available in Canada.⁹ In August 2022, other biosimilars CIMERLI and RAIVISIO were approved by the FDA ¹² and EC, respectively.¹³

Type

Biotech

Groups

Approved

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Structure

Protein Chemical Formula: C₂₁₅₈H₃₂₈₂N₅₆₂O₆₈₁S₁₂
Protein Average Weight: 48349.6111 Da (exact mass)

Sequences

>Ranibizumab Light Chain
DIQLTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

>Ranibizumab Heavy Chain
EVQLVESGGGLVQPGGSLRLSCAASGYDFTHYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPYYYGTSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHL

References:

Therapeutic Targets Database: TTD Biologic drug sequences in fasta format [Link]

Download FASTA Format

Synonyms

Ranibizumab
rhuFab V2

External IDs

RG-3645

Pharmacology

Indication

Ranibizumab injection for intravitreal use is indicated to treat Neovascular (wet) Age-related Macular Degeneration (AMD), macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, and myopic choroidal neovascularization.^7,11

Ranibizumab injection for for intravitreal use via ocular implant is used to treat Neovascular (wet) Age-related Macular Degeneration (AMD) in patients who have responded to at least two intravitreal injections of a VEGF inhibitor.⁸

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Ranibizumab is a vascular endothelial growth factor (VEGF-A) inhibitor used to manage ocular diseases with abnormal angiogenesis. It inhibits the formation of new blood vessels or neovascularization.³ Ultimately, ranibizumab works to slow down the loss of vision and causes significant visual improvement in patients with ocular degenerative disorders, such as age-related macular degeneration.⁵ It can also reduce retinal thickness.⁷

As ranibizumab has one binding site for VEGF, two drug molecules bind to one VEGF dimer.³ Ranibizumab lacks the Fc region of an antibody, which may prevent the drug from causing intraocular inflammation following intravitreal injection.⁵

Mechanism of action

The pathogenesis of neovascular eye diseases is not fully understood; however, vascular endothelial growth factor-A (VEGF-A) has been implicated in the development of clinical manifestations, such as choroidal neovascularization. Neovascularization is characterized by aberrated proliferation of abnormal vessels in the choroid capillary matrix. As a member of the VEGF family, VEGF-A is a key regulator of vascular permeability and angiogenesis;² thus, it has been studied as a therapeutic target for the treatment of a wide array of neovascular eye diseases, including neovascular (wet) age-related macular degeneration (AMD) and diabetic retinopathy.⁷ For example, increased VEGF-A levels in the vitreous were shown in patients with neovascular age-related macular degeneration.⁵

Ranibizumab is a recombinant humanized IgG1 kappa isotype monoclonal antibody directed against human VEGF-A.⁵ Ranibizumab binds to VEGF-A with high affinity as well as its biologically active forms, such as VEGF165, VEGF121, and VEGF110.⁴ Notably, VEGF165 is the most predominant isoform in the human eye that promotes ocular neovascularization. VEGF165 enhances vascular permeability, inhibits apoptosis, and causes endothelial-cell mobilization from the bone marrow and differentiation for angiogenesis.² Ranibizumab binds to the receptor-binding site of VEGF-A, preventing it from binding to its receptors - VEGFR1 and VEGFR2 - that are expressed on the surface of endothelial cells. Ranibizumab thereby attenuates endothelial cell proliferation, vascular leakage, and new blood vessel formation.⁷

Target	Actions	Organism
AVascular endothelial growth factor A	antibody	Humans

Absorption

Ranibizumab rapidly penetrates through the retina to reach the choroid after intravitreal injection.¹ Following monthly intravitreal administration of 0.5 mg ranibizumab in patients with neovascular (wet) age-related macular degeneration, the mean C_max (±SD) was 1.7 (± 1.1) ng/mL.⁷ Following an implant insertion, the mean (±SD) C_max of ranibizumab was 0.48 (±0.17) ng/mL and median T_max was 26 days, with a range of one to 89 days.⁸

Volume of distribution

The apparent volume of the central compartment (Vd/F) is 2.77 L.⁶ Ranibizumab is not shown to accumulate in serum.⁸ Due to its small size from lacking the Fc region of an antibody, ranibizumab achieves enhanced diffusion into the retina and choroid.^3,5

Protein binding

There is no information available.

Metabolism

The metabolism of ranibizumab has not been studied. Since it is a monoclonal antibody fragment, ranibizumab is expected to undergo catabolism.⁸

Route of elimination

There is no information available.

Half-life

The estimated average vitreous elimination half-life is approximately nine days following intravitreal injection.⁷ The half-life of ranibizumab implant is approximately 25 weeks.⁸

Clearance

In patients with retinal vein occlusion or diabetic macular edema, the apparent clearance (CL/F) of ranibizumab was 24.8 L/day.⁶

Adverse Effects

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Toxicity

There is no information available regarding the LD₅₀ values of ranibizumab. There is also limited clinical experience of ranibizumab overdose: concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been administered to patients, with no additional unexpected adverse reactions that were observed.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.

Drug	Interaction
Integrate drug-drug interactions in your software
Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Ranibizumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Ranibizumab.
Aducanumab	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ranibizumab.
Alendronic acid	The risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Ranibizumab is combined with Alendronic acid.
Alirocumab	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Alirocumab.
Amivantamab	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Anifrolumab.
Ansuvimab	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Ansuvimab.
Anthrax immune globulin human	The risk or severity of adverse effects can be increased when Ranibizumab is combined with Anthrax immune globulin human.

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Food Interactions

No interactions found.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
1 Ranivisio	Injection, solution	10 mg/ml	Intravitreal	Midas Pharma Gmb H	2022-12-02	Not applicable
Byooviz	Solution	10 mg / mL	Intravitreal	Samsung Bioepis Co., Ltd.	Not applicable	Not applicable
Byooviz	Injection, solution	10 mg/ml	Intravitreal	Samsung Bioepis Nl B.V.	2022-05-04	Not applicable
Byooviz	Injection, solution	10 mg/1mL	Intravitreal	Biogen Inc.	2022-06-01	Not applicable
Byooviz	Injection, solution	10 mg/ml	Intravitreal	Samsung Bioepis Nl B.V.	2021-10-06	Not applicable
Cimerli	Injection, solution	0.5 mg/0.05mL	Intravitreal	Coherus BioSciences Inc	2022-10-03	Not applicable
Cimerli	Injection, solution	0.3 mg/0.05mL	Intravitreal	Coherus BioSciences Inc	2022-10-03	Not applicable
Lucentis	Injection, solution	10 mg/ml	Intravitreal	Novartis Europharm Limited	2016-09-08	Not applicable
Lucentis	Injection, solution	10 mg/ml	Intravitreal	Novartis Europharm Limited	2016-09-08	Not applicable
Lucentis	Solution	10 mg / mL	Intravitreal	Novartis	2014-09-18	Not applicable

Chemical Identifiers

UNII: ZL1R02VT79
CAS number: 347396-82-1

References

General References

Gaudreault J, Fei D, Beyer JC, Ryan A, Rangell L, Shiu V, Damico LA: Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina. 2007 Nov-Dec;27(9):1260-6. [Article]
Kourlas H, Abrams P: Ranibizumab for the treatment of neovascular age-related macular degeneration: a review. Clin Ther. 2007 Sep;29(9):1850-61. [Article]
Vaidyanathan U, Moshirfar M: Ranibizumab . [Article]
Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M: Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res. 2007 Oct;85(4):425-30. doi: 10.1016/j.exer.2007.05.008. Epub 2007 Jun 13. [Article]
Spitzer MS, Ziemssen F, Bartz-Schmidt KU, Gelisken F, Szurman P: Treatment of age-related macular degeneration: focus on ranibizumab. Clin Ophthalmol. 2008 Mar;2(1):1-14. [Article]
Akiyode O, Dunkelly-Allen N: Ranibizumab: A Review of Its Use in the Treatment of Diabetic Retinopathy in Patients With Diabetic Macular Edema. J Pharm Technol. 2016 Feb;32(1):22-28. doi: 10.1177/8755122515599552. Epub 2015 Aug 12. [Article]
FDA Approved Drug Products: Lucentis (ranibizumab) for intravitreal injection [Link]
FDA Approved Drug Products: Susvimo (ranibizumab) for intravitreal use via ocular implantation [Link]
GlobeNewswire News Release: Health Canada Approves Samsung Bioepis and Biogen’s BYOOVIZ™ (SB11), LUCENTIS® Biosimilar (ranibizumab) [Link]
EMA Medicines: Lucentis [Link]
EMA Approved Drug Products: Lucentis (ranibizumab) intravitreal injection [Link]
FDA Approved Drug Products: CIMERLI (ranibizumab-eqrn) injection, for intravitreal use [Link]
EMA Approved Drug Products: Ranivisio (ranibizumab) Intravitreal Injection [Link]

External Links

KEGG Drug: D05697
PubChem Substance: 46506960
RxNav: 595060
ChEMBL: CHEMBL1201825
Therapeutic Targets Database: DAP001260
PharmGKB: PA164746012
RxList: RxList Drug Page
Drugs.com: Drugs.com Drug Page
Wikipedia: Ranibizumab

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Basic Science	Age - Related Macular Degeneration (AMD)	1
4	Completed	Basic Science	Diabetic Macular Edema (DME)	1
4	Completed	Basic Science	Neovascular Age-Related Macular Degeneration (nAMD)	1
4	Completed	Other	Eye Diseases / Premature Births / Retinal Diseases / Retinopathy of Prematurity Both Eyes	1
4	Completed	Other	NPDR - Non Proliferative Diabetic Retinopathy	1
4	Completed	Treatment	Age - Related Macular Degeneration (AMD)	5
4	Completed	Treatment	Age - Related Macular Degeneration (AMD) / Polypoidal Choroidal Vasculopathy (PCV)	1
4	Completed	Treatment	Age - Related Macular Degeneration (AMD) / Retinal Vein Occlusion	1
4	Completed	Treatment	Age - Related Macular Degeneration (AMD) / Subfoveal Choroidal Neovascularization (CNV)	2
4	Completed	Treatment	Branch Retinal Vein Occlusion	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Genentech Inc.
Novartis AG

Dosage Forms

Form	Route	Strength
Injection, solution	Intravitreal	0.3 mg/0.05mL
Injection, solution	Intravitreal	0.5 mg/0.05mL
Injection, solution	Intravitreal	10 MG/ML
Injection, solution	Intravitreal	10 mg/1mL
Injection, solution	Intravitreal	6 mg/1mL
Solution	Intravitreal	10 mg / mL
Injection, solution	Ophthalmic	10 mg/ml
Injection, solution	Intraocular	10 MG/ML
Injection, solution	Intraocular	2.3 mg
Injection, solution	Intraocular	1.65 mg/0.165ml
Solution	Ophthalmic	10 mg/1ml
Solution	Intraocular	2.3 mg
Injection		10 mg/ml
Injection, solution	Intravitreal	100 mg/1mL
Solution	Intravitreal	100 mg / mL

Prices

Unit description	Cost	Unit
Lucentis 0.5 mg vial	2340.0USD	vial

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
CA2286330	No	2008-06-10	2018-04-03

Properties

State

Liquid

Experimental Properties

Property	Value	Source
boiling point (°C)	100	https://www.gene.com/download/pdf/lucentis_MSDS.pdf

Targets

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Details1. Vascular endothelial growth factor A

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Antibody

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

Pieramici DJ, Avery RL: Ranibizumab: treatment in patients with neovascular age-related macular degeneration. Expert Opin Biol Ther. 2006 Nov;6(11):1237-45. [Article]
Gaudreault J, Fei D, Beyer JC, Ryan A, Rangell L, Shiu V, Damico LA: Pharmacokinetics and retinal distribution of ranibizumab, a humanized antibody fragment directed against VEGF-A, following intravitreal administration in rabbits. Retina. 2007 Nov-Dec;27(9):1260-6. [Article]
Ferrara N, Damico L, Shams N, Lowman H, Kim R: Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina. 2006 Oct;26(8):859-70. [Article]
Kourlas H, Abrams P: Ranibizumab for the treatment of neovascular age-related macular degeneration: a review. Clin Ther. 2007 Sep;29(9):1850-61. [Article]
Lowe J, Araujo J, Yang J, Reich M, Oldendorp A, Shiu V, Quarmby V, Lowman H, Lien S, Gaudreault J, Maia M: Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo. Exp Eye Res. 2007 Oct;85(4):425-30. doi: 10.1016/j.exer.2007.05.008. Epub 2007 Jun 13. [Article]

Drug created at May 16, 2007 20:14 / Updated at October 22, 2022 01:06

Ranibizumab

Identification

References:

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References