Macugen works by blocking vascular endothelial growth factor (VEGF) in the eye.
The FDA approved pegaptanib sodium (Macugen) for the treatment of neovascular age-related macular degeneration (also called exudative or wet AMD) in late 2004.
What makes pegaptanib sodium different from current treatments for age-related macular degeneration, particularly photodynamic therapy with verteporfin (Visudyne)?
Photodynamic therapy is restricted to certain subsets of people with age-related macular degeneration. And while it can help treat pre-existing abnormal blood vessels, it can’t prevent new vessels from forming. In contrast, Macugen can be used in a wider range of patients with age-related macular degeneration, and it strikes at the molecular level to get at the underlying cause of the disease. Even so, Macugen isn’t the perfect therapy for age-related macular degeneration, and challenges remain.
Macugen works by blocking vascular endothelial growth factor (VEGF) in the eye. This protein has a number of positive functions in the body— it helps preserve visual clarity in the healthy eye and it is also needed for normal wound healing and bone growth. But VEGF also stimulates or induces the process of angiogenesis (when new blood vessels develop from preexisting ones). Angiogenesis is implicated in a number of diseases, most notably cancer. In the eye, VEGF is a key factor involved in neovascularization and vascular permeability—that is, the proliferation of new vessels that are prone to leakage.
The FDA approved Macugen based on results from 2 randomized, placebo-controlled trials of 1,208 people with neovascular age-related macular degeneration. The participants were given either an injection of placebo or an injection of Macugen (either 0.3-mg, 1-mg, or 3-mg doses) every 6 weeks over a 54-week period. Although the majority of those participating in the study continued to lose vision no matter which treatment they received, moderate and severe vision loss was significantly reduced in those who received Macugen. Those who received 0.3 mg of Macugen did the best overall, with fewer people in this group experiencing severe vision loss.
Because Macugen is given by intravitreal injection, this raises the risk of endophthalmitis (a potentially blinding infection), retinal detachment, and traumatic (injection-caused) cataract. While these risks were minimal during the study, the long-term risk of a series of injections is unclear. In addition, the cost is approximately $995 per injection. With a 6-week injection schedule, that amounts to approximately $8,600 per year per person.
Future treatments for age-related macular degeneration
Macugen isn’t the only drug that targets VEGF in the eye. Ranibizumab (Lucentis), which was approved by the FDA in June 2006, also inhibits VEGF. But Lucentis takes a shotgun approach, binding all forms of VEGF (including those thought to be beneficial elsewhere in the body), while Macugen targets VEGF 165 (thought to be the most destructive form of VEGF). Only time will tell which approach will be a more effective treatment for age-related macular degeneration. In any case, the issue of repeated injections is still a problematic one. One potential way to reduce the potential for injection-related complications would be to give people with age-related macular degeneration tiny implants that deliver the drugs in a continuous, slow release over several months. Researchers are hot on this trail as well.
