Intravitreal JSM6427 (Jerini Inc) is a potent and selective inhibitor of integrin α5β1.

Animal studies have shown an inhibition of choroidal neovascularization (CNV).

This suggests that JSM6427 may provide a new approach for the treatment of age-related macular degeneration in humans.

Integrins are transmembrane receptors composed of α and β subunits that mediate binding to extracellular matrix or other cellular receptors.

Blocking angiogenesis through inhibition of integrin-mediated signaling has the potential to inhibit the cellular responses to growth factors as well as to cytokines and other inflammatory mediators⁽³⁰⁾.

Figure 3 - Alpha and Beta subunits of integrins, are transmembrane proteins. In the outer surface the subunits have an adhesive glycoprotein that interact to form a binding site. In the inner site of the cell the subunits binds with the cytoskeleton.

Volociximab (Ophthotech) is a high-affinity chimeric monoclonal antibody (Mab) that inhibits the functional activity of alpha-5 beta-1 integrin found on the endothelial cells involved in the formation of blood vessels.

“Volociximab binds to α5β1 integrin and blocks the binding of α5β1 integrin to fibronectin, thereby inhibiting a pivotal interaction required for angiogenesis.

Volociximab administration has resulted in strong inhibition of rabbit and primate retinal neovascularization.

In monkeys with laser-induced choroidal neovascularization (CNV), volociximab significantly inhibited CNV proliferation and reduced the degree of lesion formation.

In a rabbit model, volociximab administered either intravenously or intravitreally prior to the onset of neovascularization significantly reduced angiogenesis as compared to control.

Similar anti-angiogenic efficacy with volociximab has also been shown in multiple preclinical models of tumor angiogenesis.”⁽³¹⁾

A phase I open-label, multicenter study of volociximab is currently on going.

The objectives of this study are to evaluate the safety, tolerability, and pharmacokinetic profile of volociximab intravitreous injection in subjects with subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD)⁽³²⁾.