Until recently, treatment options for neovascular (wet) AMD have been limited. Thermal laser photocoagulation - a destructive mode of therapy - was indicated in a minority of neovascular cases, including extrafoveal and some cases of juxtafoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT) marked a new era in the treatment of exudative AMD, since subfoveal lesions were no longer excluded from treatment. However, it remains that not all lesions are eligible for treatment and the beneficial effect of PDT has only been clearly evident in predominantly classic lesions.
Pegaptanib sodium (Macugen) is the first anti-angiogenic drug approved by drug regulatory authorities in the US and Europe. It is an anti-vascular endothelial growth factor (VEGF) pegylated aptamer, which specifically targets VEGF165, the primary protein that is responsible for stimulating abnormal blood vessel growth and blood vessel leakage in wet AMD. As a result, pegaptanib sodium treats CNV without damaging the retina or normal vessels and is efficacious for the treatment of all forms of wet AMD, regardless of lesion subtype, size or visual acuity.
Classification of CNV has caused some confusion over recent years. The classification of lesion subtypes into predominantly classic, minimally classic and occult always appeared to be somewhat artificial and there is enormous inter- and intra-physician variability in classification. Moreover, lesions may change from initial presentation, and subtyping errors may lead to suboptimal treatment choices. Therefore, it is important to note that, regardless of its angiographic appearance, wet AMD is defined by the single disease process of CNV. With pegaptanib sodium, subtyping of CNV lesions to initiate therapy is unnecessary; therefore, potential complications related to subtyping errors can be avoided.
What did the V.I.S.I.O.N. study tell us?
The FDA and the European Commission approvals of pegaptanib sodium were supported by the results of the V.I.S.I.O.N. (VEGF Inhibition Study in Ocular Neovascularization) study, a collective term for two prospective, randomized, multicentre, double-masked, controlled clinical trials, which were analysed together.
The V.I.S.I.O.N. study1 was the largest clinical trial ever conducted in wet AMD patients. The trial enrolled 1,186 patients with baseline visual acuity in the study eye between 20/40 and 20/320 including all neovascular AMD lesion subtypes (25% predominantly classic, 36% minimally classic and 39% occult with no classic) and lesion sizes up to 12 disc areas, of which up to 50% could be comprised of subretinal haemorrhage and/or up to 25% fibrotic scar or atrophic damage. Patients had up to one prior treatment with PDT before study enrolment. In the study PDT was permitted in patients with evidence of predominantly classic disease per the FDA approved label at the discretion of the masked investigator. Therefore, the sham control group received the standard of care for neovascular AMD during the study and are thus referred to as usual care.
At one year, the study showed that pegaptanib sodium significantly reduced vision loss when compared with usual care. Among the patients receiving 0.3 mg pegaptanib sodium, 70% lost less than three lines of vision on the eye chart, compared with 55% of patients receiving usual care (p=0.0001).
In addition there was a statistically significant benefit in the change in mean visual acuity, risk of severe vision loss, risk of progression to legal blindness in the study eye, and vision maintenance in pegaptanib sodium-treated subjects compared with subjects who received usual care.
At the end of the first year (week 54), 1,053 patients were re-randomized to either continue or discontinue treatment in the second year of the study (through week 102). This randomization design allowed the study to investigate the efficacy and safety of pegaptanib in patients receiving two years of continuous treatment compared with usual care and to determine if two years of treatment with pegaptanib was better than one year of treatment.