Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: A review

Objective: This article reviews available information on the new selective vascular endothelial growth factor aptamer pegaptanib in the treatment of neovascular age-related macular degeneration (ARMD). The pharmacology, pharmacokinetics, pharmacodynamics, contraindications, and drug-interaction potential of pegaptanib are discussed, and the results of clinical trials evaluating its efficacy and tolerability are summarized. Methods: Relevant articles were identified through searches of MEDLINE (1966-June 2005) and International Pharmaceutical Abstracts (1970-June 2005). The search terms included pegaptanib sodium, Macugen, age-related macular degeneration, and choroidal neovascularization. The reference lists of identified articles were reviewed for additional publications, and further information was obtained from the manufacturer of pegaptanib. Included studies were review articles and Phase 11, 111, and IV clinical trials, with preference given to available Phase III studies. Results: Only 1 research group has evaluated the tolerability and efficacy of pegaptanib in patients with neovascular ARMD. The VEGF Inhibition Study in Ocular Neovascularization involved 2 concurrent randomized trials of intravitreous injections of pegaptanib 0.3 mg (n = 294), 1 mg (n = 300), and 3 mg (n = 296) compared with sham injections (n = 296) every 6 weeks for 54 weeks in patients with neovascular ARMD. Assessments were conducted at 6, 12, 18, 24, 30, 42, 48, and 54 weeks. The primary end point was the proportion of patients losing < 15 letters on the study eye chart at 54 weeks. This end point was achieved in 70%, 71%, and 65% of patients who received pegaptanib 0.3 (P < 0.001), 1 (P < 0.001), and 3 mg (P = 0.03), respectively, compared with 55% of those receiving the sham injections. Significant improvements in visual acuity with pegaptanib compared with the sham-injection group were seen at all time points (0.3 and 1 mg: P < 0.002; 3 mg: P < 0.05). The sham-injection group was twice as likely to have severe vision loss (loss of 30 letters or 6 lines on the eye chart) compared with those receiving pegaptanib 0.3 or 1 mg (P < 0.001). Adverse events reported significantly more often in the pegaptanib group compared with the sham-injection group included vitreous floaters (33% vs 28%, respectively; P < 0.001), vitreous opacities (18% vs 10%; P < 0.001), and anterior-chamber inflammation (14% vs 6%; P = 0.001). Injection-related adverse events during the first year of pegaptanib treatment included endophthalmitis in 12 (1.3%) patients, retinal detachment in 6 (0.7%) patients, and traumatic injury to the lens in 5 (0.6%) patients. Conclusions: There are few published clinical data on pegaptanib. In 2 clinical comparisons with sham injections, pegaptanib was well tolerated and effective in slowing the decline in visual acuity in patients with neovascular ARMD. This agent may be considered an option for the treatment of neovascular ARMD.