Ranibizumab Overview

Introduction of Ranibizumab

Ranibizumab is a monoclonal antibody fragment (Fab) created from the same parent mouse antibody as bevacizumab. Ranibizumab was developed by Genentech and is marketed in the United States by Genentech and elsewhere by Novartis, under the brand name Lucentis. Ranibizumab is used to treat wet age-related macular degeneration (AMD; an ongoing disease of the eye that causes loss of the ability to see straight ahead and may make it more difficult to read, drive, or perform other daily activities). It is also used to treat macular edema after retinal vein occlusion (an eye disease caused by blockage of blood flow from the eye that leads to blurry vision and vision loss), diabetic macular edema (an eye disease caused by diabetes that can lead to vision loss), and diabetic retinopathy (damage to the eyes caused by diabetes). It inhibits angiogenesis by inhibiting Vascular endothelial growth factor A (VEGF-A), and its effectiveness is similar to that of bevacizumab. Its rates of side effects also appear similar. However, ranibizumab typically costs $2,000 a dose, while the equivalent dose of bevacizumab typically costs $50.

Mechanism of Action of Ranibizumab

Neovascular (“wet”) age-related macular degeneration (AMD) is a pathologic age-related condition of the macula causing severe impairment of vision in people aged above 50 years. Neovascular AMD is characterized by central vision loss due to exudation, hemorrhage, and fibrovascular tissue formation secondary to pathologic choroidal neovascularization (CNV). Factors presumed to be involved in pathogenesis of CNV include ischemia, inflammation, and secretion of angiogenic factors, such as vascular endothelial growth factor (VEGF), which is a homodimeric glycoprotein that has been isolated from CNV membranes obtained from patients with AMD. VEGF belongs to a family of dimeric glycoproteins within the superfamily of PDGFs. While VEGF, also known as VEGF-A, is the most comprehensively studied, other members of this family include VEGF-B, VEGF-C, VEGF-D, and PLGF. VEGF-A has several isoforms that arise from alternative splicing. All VEGF ligands bind to tyrosine kinase receptors, causing the receptors to dimerize and autophosphorylate. Upon binding to its receptor, VEGF initiates a cascade of signaling events that begins with auto-phosphorylation of both receptor kinases, followed by activation of numerous downstream proteins, including phosphoinositide-3-kinase (PI3K), the Ras GTPase activating protein, Ras, mitogenactivated protein kinase (MAPK), and others. VEGF-A binds to VEGF receptor (VEGFR)-1 and VEGFR-2. VEGF promotes the growth, migration, and proliferation of endothelial cells. In addition, VEGF induces vasodilatation and enhances endothelial cell survival. These biologic activities occur in few physiologic processes outside wound healing and ovulation, making VEGF an attractive target for therapy. Ranibizumab binds to VEGF-A, and thereby inhibits the binding of VEGF-A to its receptors, neutralizing the biological activity of VEGF-A and regressing the vascularization, thereby inhibiting the AMD process.

Fig.1 Mechanism of action of Ranibizumab

Table 1. Clinical Projects of Ranibizumab*

Table 2. Approved Drugs of Ranibizumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Lucentis	Neovascular (Wet) Age-Related Macular Degeneration, Macular Edema Following Retinal Vein Occlusion, Diabetic Macular Edema, Diabetic Retinopathy, Myopic Choroidal Neovascularization	Solution for injection	10 mg / mL	Intravitreal Injection	Genentech	June 30, 2006
Lucentis	Wet Macular Degeneration, Macular Edema Myopia, Degenerative Diabetes Complications	Solution for injection	10 mg / mL	Intravitreal Injection	Novartis Europharm Limited	January 22, 2007
Lucentis	Neovascular (Wet) Age-Related Macular Degeneration, Macular Edema Following Retinal Vein Occlusion, Diabetic Macular Edema, Diabetic Retinopathy, Myopic Choroidal Neovascularization	Solution for injection	10 mg / mL	Intravitreal Injection	Novartis Pharma Corporation	January 21, 2009
Lucentis	Neovascular (Wet) Age-Related Macular Degeneration, Macular Edema Following Retinal Vein Occlusion, Diabetic Macular Edema, Diabetic Retinopathy, Myopic Choroidal Neovascularization	Solution for injection	10 mg / mL	Intravitreal Injection	Novartis Pharmaceuticals Canada Inc	July 26, 2007
Lucentis	Neovascular (Wet) Age-Related Macular Degeneration, Macular Edema Following Retinal Vein Occlusion, Diabetic Macular Edema, Diabetic Retinopathy, Myopic Choroidal Neovascularization	Solution for injection	10 mg / mL	Intravitreal Injection	Novartis Pharmaceuticals Australia Pty Ltd	May 11, 2013

What We Provide

Therapeutic Antibody

Ranibizumab

We provide high-quality Ranibizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

Reference
* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Ranibizumab

** Information presented in the table were collected from the following websites:
http://search.tga.gov.au/s/search.html?collection=tga-artg&profile=record&meta_i=212387
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=25156
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000715/human_med_000890.jsp
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=78217
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/1319403A1

For research use only. Not intended for any clinical use.