New drugs in development for age-related macular degeneration (AMD).
Ease of administration
Currently available AMD therapies, such as ranibizumab (Lucentis, Genentech) or the off-label use of Genentech's bevacizumab (Avastin), require monthly intravitreal injections. Several companies are attempting to overcome the tedious process by developing AMD therapies that can be administered with the ease of eyedrops.
Also being investigated as an ophthalmic solution to treat AMD is ATG3 from CoMentis. This topical and noninvasive treatment inhibits endothelial nicotinic acetylcholine (nACh) receptors and has been shown to decrease angiogenesis and vascular permeability. Currently, ATG3 is in a phase II study designed to assess safety in patients with neovascular AMD. The company expects six-month data by the middle of 2008.
Regeneron Pharmaceuticals and Bayer HealthCare initiated a phase III trial in August of this year to evaluate VEGF Trap-Eye, a fully human soluble vascular endothelial growth factor (VEGF) receptor fusion protein that binds to all forms of VEGF-A, along with placental growth factor, for the treatment of wet AMD. The anti-angiogenic agent will be stacked up against ranibizumab in a comparative trial involving approximately 1,200 patients. The study, VIEW1, will compare VEGF Trap-Eye at doses of 0.5 mg and 2 mg at four-and eight-week dosing intervals with 0.5 mg ranibizumab every four weeks.
Results of an earlier phase II trial showed VEGF Trap-Eye met its primary endpoint of a statistically significant reduction in retinal thickness after 12 weeks of treatment. Regeneron received a $20 million milestone payment from partner Bayer HealthCare upon dosing of the first patient in the phase III study.
Traditional and novel approaches
Because of the retina's susceptibility to oxidative damage, many believe that supplementation with antioxidants could have a major impact on progression of the disease. In fact, results of the age-related eye disease study (AREDS) showed that antioxidants are useful for the prevention and progression of AMD. Patients receiving vitamins C and E, zinc, and beta-carotene had a 28% reduction in the risk of progression to advanced AMD compared with placebo. AREDS-2 now seeks to assess the effects of lutein, zeaxanthin, and long-chain omega-3 fatty acids on the progression to advanced AMD. Enrollment in this study is expected to conclude by December 2007.
GenVec Inc. seeks a novel solution to AMD. This company is in phase I with AdPEDF, a therapy that utilizes an adenovector DNA carrier to deliver the human pigment epithelium-derived factor (PEDF) gene. AdPEDF inhibits abnormal blood vessel growth and protects the photoreceptors which can be damaged by leaky blood vessels.