Treatment-related Safety Research Articles

Anecortave Acetate for the Treatment of Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.

Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration: twelve-month clinical outcomes

Purpose To evaluate safety and efficacy of the angiostatic agent anecortave acetate, compared with a placebo, for treatment of subfoveal choroidal neovascularization (CNV). Design Ongoing masked, randomized, placebo-controlled, parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a placebo. Participants There were 128 eyes of 128 patients with subfoveal CNV secondary to age-related macular degeneration who were enrolled and treated, with 80% (102/128) of eyes presenting with predominantly classic lesions at baseline. Methods All eyes received a posterior juxtascleral depot application of masked study medication or a placebo, with retreatment at 6-month intervals if the masked investigator believed the patient could benefit. Patients received periodic detailed ophthalmic examinations with both fluorescein and indocyanine green angiography, general physical examinations with electrocardiograms, and hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data were periodically reviewed by the Independent Safety Committee overseeing the study. Main outcome measures Best-corrected logarithm of the minimum angle of resolution (logMAR) vision and fluorescein angiographic lesion characteristics were compared over time and among treatment groups. Results At month 12, anecortave acetate (15 mg) administered at 6-month intervals was statistically superior to the placebo for 3 measures of clinical efficacy: mean change from baseline vision ( P = 0.0131), stabilization of vision (<3 logMAR line change; P = 0.0323), and prevention of severe vision loss (decrease of ≥6 logMAR lines from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions revealed that anecortave acetate (15 mg) was also superior to the placebo at 1 year for each of these 3 measures of visual outcome ( Ps = 0.0022, 0.0100, and 0.0299, respectively). Anecortave acetate (15 mg) trended toward significance over the placebo at month 12 for inhibition of total lesion growth and for inhibition of both the total CNV component and the classic CNV component in both the overall and subgroup analyses. The Independent Safety Committee identified no clinically relevant treatment-related safety issues. Conclusions Anecortave acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion growth.