West Coast Editor

The "eyes" have it, and only one treatment exists.

That's why Alcon Research Ltd. said it began enrolling 500 patients in a Phase III study comparing its modified steroid, Anecortave Acetate, with Visudyne (verteporfin), QLT Inc.'s marketed treatment for age-related macular degeneration.

The two-year study will take place at 40 to 50 sites in the U.S., Canada, Australia and Europe, comparing vision outcomes for patients treated with 15 mg of Anecortave Acetate to those for patients treated with Vancouver, British Columbia-based QLT's photodynamic therapy, approved in 2000.

Aiming, like Visudyne, mainly at the wet form of AMD - in which blood vessels grow and leak, separating the macula from the retinal tissue - the trials will administer Alcon's drug or placebo four times. Also, patients will be given, at least once and possibly up to eight times, either Visudyne with laser-activating treatment, or a solution of sugar water plus the laser light (which will have no effect on placebo patients).

Although the wet form of AMD makes up only 10 percent to 15 percent of cases, it's responsible for most blindness caused by AMD. Vision loss begins around age 55 and can result in "social blindness" in two to three years.

Anecortave acetate, injected every six months around the back of the eye, is intended to slow or stop the growth of new blood vessels under the retina. It's given during an in-office procedure, unlike other therapies being investigated that require direct injection into the eye between nine and 12 times each year.

Others developing AMD treatments are EyeTech Pharmaceuticals Inc., of New York, with enrollment of Macugen - an aptamer designed to bind and neutralize vascular endothelial growth factor - completed in a pair of Phase III trials; and Genentech Inc., of South San Francisco, which has an antivascular endothelial growth factor antibody in much earlier development.

Mohammad Azab, senior vice president of clinical research for QLT, told BioWorld Today the two treatments are "really not comparable. There's no indication they're going to get any better efficacy."

Alcon, of Fort Worth, Texas, said that in its Phase II/III trials, as of July, 62 patients had been re-treated at least three times with Anecortave Acetate and 16 patients had received five applications, with results over placebo still positive. The company has 12-month data so far, and more details will be offered at the Retina Congress 2002 in San Francisco next month.

"[QLT's Visudyne] data comes from very large Phase III trials, 400 treatment patients and 200 placebo," Azab said, whereas Alcon tested only 30 patients per arm.

Jason Slakter, lead physician in the Alcon studies and retinal specialist at Vitreous-Retina-Macula Consultants of New York, as well as professor of ophthalmology at the New York University School of Medicine, conceded the two trials are vastly different in size.

"It's not fair to do a direct comparison, but it's the rationale for the design of the study," he told BioWorld Today. Although the Phase II/III study was small, it showed 92 percent of Anecortave acetate vs. 70 percent of Visudyne patients maintained vision with less than three lines of vision loss, measured on an eye chart.

Also, he said, Alcon's patients showed improvement.

"Visudyne's primary goal is stabilization, but at six months, 18 percent [of Anecortave acetate patients] had improved by two lines or more," Slakter said.

He added that, as an expert, he has spoken in an unpaid capacity for both treatments.

Alcon's drug "stays outside the eye, and it's [given] every six months," he said. "Visudyne [injected into the arm] is given every three months. Genentech's is every four weeks, and EyeTech's is every six weeks."

Anecortave acetate's injection near the back of the eye "takes about two minutes," Slakter said, after a sterile environment is created. "It's relatively innocuous. We thought this would be a major issue, but patients will tell you that was no big deal, and it didn't hurt, and it was just a little pinch."

QLT marches on. Last month, the company and Novartis Ophthalmics, the eye health unit of Novartis AG, of Basel, Switzerland, completed enrollment for the treatment in an early retreatment Phase IIIb trial in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD. The study is investigating an earlier, more aggressive and frequent treatment regimen. Results are expected in the fourth quarter of 2003.

Also last month, Visudyne, which selectively targets abnormal blood vessels on the retina, was granted marketing approval from the European Commission for the treatment of occult subfoveal choroidal neovascularization secondary to AMD. The approval includes all patients with that indication who have recent or ongoing disease progression.

Azab said "there's always room for competition," noting that "the market is big," with about 500,000 wet AMD patients, of whom about 125,000 have the predominantly classic form as determined by angiographic diagnosis, for which Visudyne is approved in the U.S. and for which Alcon's treatment is seeking approval.

Slakter said that, "for 30 years, there was conventional laser [treatment for leaking eye vessels] or nothing. This is an exciting time."

QLT's stock (NASDAQ:QLTI) rose 1 cent Wednesday to close at $7.92.