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, 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 EMA 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, ranibizumab-eqrn, a biosimilar marketed as CIMERLI, was approved by the FDA.12

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:
  1. 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

TargetActionsOrganism
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 Cmax (±SD) was 1.7 (± 1.1) ng/mL.7 Following an implant insertion, the mean (±SD) Cmax of ranibizumab was 0.48 (±0.17) ng/mL and median Tmax 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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Ranibizumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ranibizumab.
AducanumabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Aducanumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ranibizumab.
Alendronic acidThe risk or severity of jaw osteonecrosis and anti-angiogenesis can be increased when Ranibizumab is combined with Alendronic acid.
AlirocumabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Alirocumab.
AmivantamabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Amivantamab.
AnifrolumabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Anifrolumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Ranibizumab is combined with Ansuvimab.
Anthrax immune globulin humanThe 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
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
ByoovizSolution10 mg / mLIntravitrealSamsung Bioepis Co., Ltd.Not applicableNot applicableCanada flag
ByoovizInjection, solution10 mg/1mLIntravitrealBiogen Inc.2022-06-01Not applicableUS flag
ByoovizInjection, solution10 mg/mlIntravitrealSamsung Bioepis Nl B.V.2022-05-04Not applicableEU flag
ByoovizInjection, solution10 mg/mlIntravitrealSamsung Bioepis Nl B.V.2021-10-06Not applicableEU flag
LucentisInjection, solution10 mg/mlIntravitrealNovartis Europharm Limited2016-09-08Not applicableEU flag
LucentisInjection, solution10 mg/mlIntravitrealNovartis Europharm Limited2016-09-08Not applicableEU flag
LucentisInjection, solution10 mg/mlIntravitrealNovartis Europharm Limited2016-09-08Not applicableEU flag
LucentisSolution10 mg / mLIntravitrealNovartis2014-09-18Not applicableCanada flag
LucentisInjection, solution6 mg/1mLIntravitrealGenentech, Inc.2012-08-10Not applicableUS flag
LucentisInjection, solution10 mg/mlIntravitrealNovartis Europharm Limited2016-09-08Not applicableEU flag

Categories

ATC Codes
S01LA04 — Ranibizumab
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 and other mammals

Chemical Identifiers

UNII
ZL1R02VT79
CAS number
347396-82-1

References

General References
  1. 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]
  2. 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]
  3. Vaidyanathan U, Moshirfar M: Ranibizumab . [Article]
  4. 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]
  5. 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]
  6. 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]
  7. FDA Approved Drug Products: Lucentis (ranibizumab) for intravitreal injection [Link]
  8. FDA Approved Drug Products: Susvimo (ranibizumab) for intravitreal use via ocular implantation [Link]
  9. GlobeNewswire News Release: Health Canada Approves Samsung Bioepis and Biogen’s BYOOVIZ™ (SB11), LUCENTIS® Biosimilar (ranibizumab) [Link]
  10. EMA Medicines: Lucentis [Link]
  11. EMA Approved Drug Products: Lucentis (ranibizumab) intravitreal injection [Link]
  12. FDA Approved Drug Products: CIMERLI (ranibizumab-eqrn) injection, for intravitreal use [Link]
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
PhaseStatusPurposeConditionsCount
4Active Not RecruitingBasic ScienceNeovascular Age-Related Macular Degeneration (nAMD) / Polypoidal Choroidal Vasculopathy (PCV)1
4Active Not RecruitingTreatmentDiabetic Macular Edema (DME)1
4Active Not RecruitingTreatmentWet Macular Degeneration1
4CompletedBasic ScienceAge - Related Macular Degeneration (AMD)1
4CompletedBasic ScienceDiabetic Macular Edema (DME)1
4CompletedBasic ScienceNeovascular Age-Related Macular Degeneration (nAMD)1
4CompletedOtherEye Diseases / Premature Births / Retinal Diseases / Retinopathy of Prematurity Both Eyes1
4CompletedOtherNPDR - Non Proliferative Diabetic Retinopathy1
4CompletedTreatmentAge - Related Macular Degeneration (AMD)5
4CompletedTreatmentAge - Related Macular Degeneration (AMD) / Polypoidal Choroidal Vasculopathy (PCV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Genentech Inc.
  • Novartis AG
Dosage Forms
FormRouteStrength
Injection, solutionIntravitreal
Injection, solutionIntravitreal0.5 mg/0.05mL
Injection, solutionIntravitreal10 mg/1mL
Injection, solutionIntravitreal10 MG/ML
Injection, solutionIntravitreal6 mg/1mL
SolutionIntravitreal10 mg / mL
Injection, solutionOphthalmic
Injection, solutionIntraocular10 MG/ML
Injection, solutionIntraocular2.3 mg
Injection, solutionIntraocular1.65 mg/0.165ml
SolutionOphthalmic10 mg/1ml
SolutionIntraocular2.3 mg
Injection10 mg/ml
Injection, solutionIntravitreal100 mg/1mL
Prices
Unit descriptionCostUnit
Lucentis 0.5 mg vial2340.0USD vial
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2286330No2008-06-102018-04-03Canada flag

Properties

State
Liquid
Experimental Properties
PropertyValueSource
boiling point (°C)100https://www.gene.com/download/pdf/lucentis_MSDS.pdf

Targets

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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
  1. 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]
  2. 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]
  3. 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]
  4. 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]
  5. 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 September 02, 2022 17:58