Squalamine lactate for the treatment of age-related macular degeneration

Abstract

Squalamine lactate (Evizon™, Genaera, PA, USA) is a systemically administered antiangiogenic compound that is among the group of drugs being investigated for the treatment of neovascular age-related macular degeneration (AMD). Squalamine lactate is the first drug candidate from the aminosterol class and has a unique and multifaceted mechanism of action. Both preclinical evaluations and clinical studies have demonstrated promise for the treatment of AMD and various cancers. In contrast to antibody-based antiangiogenic compounds, squalamine lactate has a more generalized effect on the cellular signaling cascades that are common to vascular endothelial growth factor and other growth factors, including basic fibroblast growth factor (FGF2), platelet-derived growth factor and thrombin. Due to its systemic (intravenous) mode of delivery, squalamine lactate avoids the severe potential complications (i.e., endophthalmitis, ocular inflammation, vitreous hemorrhage and traumatic cataract) associated with intraocular injections. In addition, hypertension, often severe, related to systemic use of antiangiogenic agents such as bevacizumab has been reported. To date, during therapy in clinical studies, squalamine has not demonstrated acute hypertension, any secondary effects on the cardiovascular system or any pattern of drug-related cardiovascular adverse events. In contrast to intravitreal agents, both eyes are treated simultaneously with a single infusion allowing for therapy in subjects with bilateral exudative AMD. The objective of this article is to summarize the basic science, pharmacokinetic, pharmacodynamic activity, safety and efficacy of squalamine lactate for the treatment of choroidal neovascularization associated with AMD.