Inhibitors for Eye Disease

Angiogenesis in the eye underlies the major causes of blindness in both developed and developing nations, including exudative age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), central retinal vein occlusion (CRVO), neovascular glaucoma, corneal neovascularization (trachoma), and pterygium. Presently approved anti-angiogenic therapies for ophthalmic conditions are biologic agents that inhibit VEGF. There are currently three approved antiangiogenic therapies for ophthalmic diseases: an anti-VEGF aptamer (pegaptanib, Macugen); a Fab fragment of a monoclonal antibody directed against VEGF-A (ranibizumab, Lucentis); and a fusion protein that binds to VEGF-A, VEGF-B, and PlGF (afilbercept, Eylea).

Monoclonal Antibody Therapy
One monoclonal antibody therapy is approved to treat Age-related macular degeneration (AMD), a progessive eye diease that results in loss of central vision, and is the leading cause of severe vision loss in adults over the age of 65. The wet form of AMD accounts for 10% of advanced cases, and is characterized by the abnormal growth of new blood vessels, which leak fluid and blood, inducing scar formation and destroying vision.
Ranibizumab (Lucentis®)
Description

Genentech
A recombinant humanized IgG1 kappa monoclonal antibody fragment that binds vascular endothelial growth factor-A (VEGF-A) and cleavage products, and prevents their interaction with VEGF receptors (VEGFR-1 and VEGFR-2), thereby inhibiting endothelial cell proliferation, angiogenesis, and vascular leakage in the retina and choroidal layers.

Approved Indications

Neovascular (wet) age-related macular degeneration,
Macular edema after retinal vein occlusion,
Visual impairment due to diabetic macular edema (EU only)

  • Administered by intravitreal injection.

 
 

 

Aptamer
Pegaptanib (Macugen®)
Description

Eyetech Inc.
A pegylated modified oligonucleotide (aptamer) which adopts a three dimensional conformation that enables it to bind to extracellular VEGF, thereby inhibiting its binding to VEGF receptors and suppressing pathological neovascularization.

Approved Indications

Neovascular (wet) age-related macular degeneration

  • Administered by intravitreal injection.

 
 

 

Fusion Protein

Aflibercept (Eylea©)
Description

Regeneron Pharmaceuticals and Bayer AG
A fusion protein that functions as an inhibitor of vascular endothelial growth factors. It is designed to bind to VEGF-A, VEGF-B, and placental growth factor (PlGF).

Approved Indications

Neovascular (wet) age-related macular degeneration

  • Administered by intravitreal injection.

Macular edema following Retinal Vein Occlusion (RVO)

  • Administered by intravitreal injection.

Myopic Choroidal Neovascularization

  • Approved in Japan.

 

Conbercept (Compaq Siqq)
Description

Chengdu Kanghong Biotechnology Co. Ltd.
A fusion protein consisting of the extracellular domain 2 of VEGFR1 and extracellular domains 3 and 4 of VEGFR2 combined with the Fc portion of the human immunoglobulin G1.

Approved Indications

Wet AMD

 

 

 

Corticosteroid Implant
Ozurdex©
Description

Allergan Retina
A sustained-release, biodegradable corticosteroid implant injected into the eye which contains 0.7 mg of the dexamethasone, is injected into the vitreous of the eye and gradually releases medicine over time.

Approved Indications

Macular Edema

  • Following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)

Diabetic Macular Edema (DME)

  • For adults with DME who have had an artificial lens implant, or scheduled for cataract surgery

Uveitis (noninfectious inflammation of the uvea)

  • Affecting the back segment of the eye

 
Iluvien©
Description

Allergan Retina
A sustained release corticosteroid implant which contains 0.00023 mg of fluocinolone acetonide (FA), which is injected into the vitreous of the eye and is designed to release the medicine gradually for up to three years.

Approved Indications

Diabetic Macular Edema (DME)

  • Approved in the United States, Austria, Denmark, France, Germany, Italy, Norway, Portugal, Spain, Sweden and the United Kingdom for treating vision impairment associated with chronic DME considered insufficiently responsive to available therapies.