of patients that must be enrolled to have a reasonable probability of detecting a statistical difference between the treatment groups and the follow-up period is usually long. The Anecortave Acetate Risk Reduction Trial (AART) was designed to demonstrate that anecortave acetate suspension (15 mg or 30 mg) is safe and effective in arresting the progression of non-exudative (dry) AMD in patients who are at-risk for progressing to exudative (wet) AMD. The primary outcome measure of this study is the percentage of patients with sight-threatening CNV in the study eye at month 48. The study is being conducted at over 100 centers across the US, Europe, Australia and South America. Enrollment of more than 2500 patients was completed at the end of 2005. Role of RETAANE As discussed above, RETAANE suspension is an effective and safe treatment for patients with wet AMD. Use as monotherapy is supported by the dose-response study (C- 98-03) comparing efficacy of RETAANE 15 mg versus placebo and the demonstration of equivalence of RETAANE 15 mg and Visudyne PDT over 24 months (C-01-99). An alternative role for RETAANE 15 mg as an adjunct or in combination to anti-VEGF therapy may be considered because of its unique, multifactorial mechanism of action, 6 month duration of action and safety due to the PJD procedure. In addition, RETAANE suspension has been demonstrated to be safe for use with Visudyne PDT (see C- 00-07 above). Not known at this time is whether RETAANE 15 mg given by PJD administration can potentiate the efficacy of intravitreal anti-VEGF therapy and reduce the frequency of intravitreal injections associated with the anti- VEGF approach. To further address this interesting issue, Alcon Research Ltd., is collaborating with the National Eye Institute to conduct the BRIDGE Study which is a randomized, masked, multi-center, phase II study of the effect of PJD delivery of RETAANE 15 mg on the response to intravitreal bevacizumab (Avastin™) in patients with subfoveal CNV secondary to AMD. The objective of this study will be to investigate whether RETAANE 15 mg (anecortave acetate suspension) reduces the frequency of intravitreal injections while maintaining vision and limiting disease progression in patients who are receiving intravitreal injections of bevacizumab (Avastin) for treatment of exudative AMD. Finally, due to the characteristics of RETAANE suspension (ie, mechanism of action, safety, and chronic duration following PJD Clinical Interventions in Aging 2006:1(3) Anecortave acetate in age-related macular degeneration administration), the drug may be suited for arresting the conversion of dry AMD to wet AMD in patients at risk for developing CNV associated with AMD (AART Study). If approved for arresting the progression of CNV, RETAANE 15 mg would be the only therapy, with the exception of AREDS vitamin supplement, to inhibit progression of any AMD subtype. Regulatory status RETAANE suspension was approved in Australia on December 12, 2005. On May 24, 2005 the US Food and Drug Administration (FDA) issued an approvable letter for the RETAANE 15mg (anecortave acetate suspension) new drug application (NDA). In March 2006, Alcon has withdrawn the application for approval at the European Medicines Agency (EMEA). Conclusion A synthetic cortisone (anecortave acetate) has been shown to have antiangiogenic properties that have been established in multiple experimental models of angiogenesis. Clinical trials in patients with exudative AMD have demonstrated an excellent safety record both for anecortave acetate and the PJD administration, with no clinically relevant adverse events. Co-administration of anecortave acetate 15 mg with PDT has been shown to be safe. Patients receiving one anecortave acetate administration and one PDT treatment showed a trend toward better visual outcomes than patients receiving multiple PDT treatments. In addition, treatment with anecortave acetate 15 mg reduced the need for future PDT treatments. AMD is viewed as a multifactorial disease by most retina specialists, and as such it is likely that a combination of drugs will result in a better visual acuity outcome than a mono-therapy approach in this disease. In addition, a second goal of all new treatment strategies is the reduction of retreatments being necessary for a complete regression of the CNV. With its mechanism of action, excellent safety profile, and innovative delivery method once every six months, RETAANE suspension may function to assist not only in controlling the CNV either alone or as a component of combination therapy, but also as a treatment for reducing the risk of the development of wet AMD. The results from the AART study could thus be an important milestone for AMD treatment options. 245