Genaera Corporation has initiated the Phase 1-2 clinical trial designed to test squalamine, an angiogenesis inhibitor, for the treatment of the "wet" (choroidal neovascularization) age-related macular degeneration (AMD).
The study is an open label, dose escalation study, designed to evaluate 40 patients with AMD for safety and efficacy of squalamine treatment. Patients enrolled will have careful angiographic and clinical documentation of their AMD at baseline. Enrollment will include AMD patients with each angiographic subtype of choroidal neovascularization, including classic, occult, and mixed angiographic abnormalities. Each patient will be treated with squalamine, once weekly for 4 weeks. Squalamine will be administered intravenously at doses of 25 or 50 mg/m2.
The study will be performed with leading ophthalmologists in Mexico, in consultation with Dr. Charles Garcia, Professor of Ophthalmology, University of Texas, and Dr. Gholam Peyman, Professor of Ophthalmology, Tulane University. Genaera currently anticipates completing this study in the first half of 2003.
Systemically administered squalamine inhibits abnormal angiogenesis in rodent models of retinopathy of prematurity, and the development of choroidal neovascular membranes in rat models of AMD. Additional preclinical studies have demonstrated that systemic squalamine administration is effective in reaching abnormal ocular blood vessels in primates, and leads to partial regression and inhibition of new abnormal vessels in the eye. The dose for squalamine to produce these effects in primates is less than 10% of that currently being used successfully in squalamine clinical trials for patients with advanced cancers. These results support that squalamine may have a role in the treatment of human choroidal neovascular membrane formation that underlies the pathology of "wet" AMD.
Angiogenesis resulting from AMD is the leading cause of legal blindness among adults age 50 or older in the Western world. About 25-30 million people are affected globally. This number is expected to triple over the next 25 years.
AMD appears to come in two types: the "dry" form and the more severe "wet" form. Dry AMD, the more common and milder form of AMD, accounts for 85% to 90% of all cases. Dry AMD results in varying forms of sight loss and may or may not eventually develop into the wet form. Although the wet form of AMD accounts for only 10% to 15% of all AMD, the chance for severe sight loss is much greater. It is responsible for 90% of severe vision loss associated with AMD. Approximately 500,000 new cases of wet AMD are diagnosed annually worldwide. In North America alone, approximately 200,000 new cases of wet AMD are diagnosed each year. Wet AMD is caused by the growth of abnormal blood vessels, or choroidal neovascularization, under the central part of the retina, the macula.