Two drugs currently in testing have performed well against advanced age-related macular degeneration (AMD). Bevasiranib (Opko Health, Inc.) is a gene-silencing agent aimed at reducing the production of vascular endothelial growth factor (VEGF). Endostatin, an experimental cancer drug, restricts the growth of abnormal blood vessels. Both could potentially play a significant role in halting the progress of AMD.
Bevasiranib. The small interfering RNA (siRNA) drug bevasiranib will be in phase III clinical trials soon. The Combining Bevasiranib and Lucentis Therapy (COBALT) study is now enrolling patients.1 Bevasiranib is a synthetic double-strand of RNA that silences the genes responsible for production of VEGF. It is administered by intravitreal injection.
Over a period of 104 weeks, the COBALT study will examine three treatment options: treatment with Lucentis (ranibizumab, Genentech) every four weeks, three injections of Lucentis followed by bevasiranib injections every eight weeks, or three Lucentis injections followed by injections of bevasiranib every 12 weeks. The COBALT trial is projected to run until August 2010.
Current vision-preserving therapy requires patients with wet AMD to receive intravitreal injections every four weeks, says Phillip Frost, M.D., CEO of Opko Health. So, the potential ability of bevasiranib to achieve similar results while requiring less frequent injections would be an important benefit for these patients, who often have limited mobility.
Endostatin. Harvard investigators tested endostatin in mice as a method of controlling ocular angiogenesis in cases of advanced AMD.2 Two groups of mice were examined: one control group and one genetically altered to be endostatin-deficient. When choroidal neovascularization was induced, the lesions were three times smaller in mice with endostatin than in those without it. And, when endostatin was administered to the altered mice, their lesions became similar in size and presentation compared to those of the control mice.
Endostatin is a protein found in collagen that inhibits angiogenesis without inciting resistance to treatment. Currently, it is also being tested in patients with cancer to quell abnormal blood vessel formation and limit the supply of blood to tumors.3
Our study provides intriguing findings that may lead to a better treatment of age-related macular degeneration, says lead researcher Alexander Marneros, M.D. But, clinical studies in humans with AMD are yet to be done, he says.
(See Therapy for AMD: Whats in the Pipeline" for more emerging AMD treatments.)
1. National Institutes of Health. Clinical Trial. Safety & Efficacy Study Evaluating the Combination of Bevasiranib & Lucentis Therapy in Wet AMD (COBALT). December 2007. Available at: www.clinicaltrials.gov/ct2/show/ NCT00499590?term=bevasiranib&rank=1 (Accessed December 28, 2007).
2. Marneros AG, She H, Zambarakji H, et al. Endogenous endostatin inhibits choroidal neovascularization. FASEB J 2007 Dec;21(14):3809-18.
3. Hajitou A, Grignet C, Devy L, et al. The antitumoral effect of endostatin and angiostatin is associated with a down-regulation of vascular endothelial growth factor expression in tumor cells. FASEB J 2002 Nov;16(13):1802-4.
