Vision-loss Drug Eyes Success

DRUG DEVELOPMENT

With its positive phase III clinical trial results, Genentech's experimental drug Lucentis has grabbed the spotlight among treatments being developed for wet age-related macular degeneration, or wet AMD. This leading cause of straight-ahead, central vision loss in patients over age 50 can progress to blindness.

According to Genentech, in a trial with 716 patients, 95% of patients treated with Lucentis "maintained or improved vision" and had significantly improved visual acuity.

The news sent the stock of biotech company Eyetech Pharmaceuticals into a 46% plunge. In December 2004, Eyetech and its partner Pfizer received approval for wet AMD treatment Macugen, the much-celebrated first in a new class of ophthalmic drugs that target vascular endothelial growth factor (VEGF). In Eyetech's clinical trials, however, vision improvement or stabilization was found in only 70% of patients.

VEGF is a signaling protein crucial in abnormal blood vessel growth. The leakiness of these blood vessels is part of the progression of wet AMD to vision loss. Both drugs must be injected directly into the eye, and both attack VEGF, although they differ in the forms of VEGF to which they bind.

The Genentech trial results have the makings of a showdown between a biopharmaceutical and a chemically synthesized product. Macugen is based on an oligonucleotide developed at Eyetech and manufactured by Degussa's Raylo Chemicals unit. Lucentis is a humanized therapeutic antibody fragment developed and manufactured by Genentech. It is a cousin of the firm's colon cancer drug Avastin and, according to a spokeswoman, is based "on the same concept and the same science of angiogenesis," or blood vessel growth.

Other companies are active in the wet AMD area with drugs based on other modes of action. They include QLT, which markets Visudyne, the very first treatment approved for wet AMD, and Alcon, whose steroid Retaane just received conditional FDA approval.