A Phase I/II Trial of Intravenous Squalamine Lactate for Treatment of Choroidal Neovascularization in Age Related Macular Degeneration (ARMD).

Abstract

Abstract: : Purpose: To assess the visual acuity (VA), Fluorescein Angiography (FA), Fundus Photography (FP), and safety outcomes of patients with Classic, Occult, and Mixed CNV lesions. High recurrence incidences are common following administration of the currently available treatments for CNV associated with ARMD. Squalamine is an aminosterol with anti–angiogenic activity in various ocular angiogenesis animal models. It has been shown to inhibit the signaling pathway of Vascular Endothelial Growth Factor (VEGF), which is a key regulators of angiogenesis in these models. Methods: A prospective study was performed. Patients who met eligibility criteria received weekly intravenous infusions of squalamine lactate either at the doses of 25 and 50 mg/m² at various durations of infusion (180, 90, 45 minutes) for 4 weeks. Baseline VA, FA, and FP were performed. All patients were evaluated weekly and at the end of treatment, followed by two follow up visits at 2 and 4 months following the initiation of the treatment. VA was monitored using the ETDRS chart, and FA/FP assessment following the MPS guidelines. Results: 40 patients were enrolled. 17 (43%) were male and 23 (57%) female. Ages ranged from 51–92 years. Ten patients (26%) had three lines or greater improvement in visual acuity, and 29 (74%) maintained their initial VA or had less than 3 lines of VA loss at the 4 month visit. The greatest improvement in VA was 8 lines, from 20/125 to 20/20. There were no significant adverse events reported. Conclusions:Squalamine is effective in improving VA in a number of patients with "wet ARMD" and commonly prevents moderate loss of vision. Squalamine only inhibits new vessel formation without significant regression of existing lesions in most of the patients. Further studies using squalamine in combination with adjunctive therapies should be performed.

Keywords: choroid: neovascularization • age–related macular degeneration • clinical (human) or epidemiologic studies: treatment/prevention assessment/controlled clinical trials