By Lisa Seachrist

Washington Editor

BETHESDA, Md. - Noting the therapy was no panacea for age-related macular degeneration (AMD), an FDA advisory panel lent its support for approval of QLT PhotoTherapeutics Inc.'s Visudyne (verteporfin), a light-activated therapy for the treatment of "wet-form" AMD.

The Ophthalmic Drugs Subcommittee of the Dermatologic & Ophthalmic Drugs Advisory Committee didn't vote on whether or not to recommend approval of the therapy developed by Vancouver, British Columbia-based QLT in conjunction with Atlanta-based CIBA Vision Corp., the eye-care unit of Novartis AG. Nevertheless, the committee endorsed approval of the therapy in comments to the agency.

"This drug isn't a panacea," said panel member George (Jack) Cioffi, an ophthalmologist at the Devers Eye Institute in Portland, Ore. "The treatment effect is modest. On the other hand, AMD is a terrible disease. I think this is a reasonable drug, and we should recommend approving it."

"This panel hearing is a significant milestone for Visudyne therapy, but it's a more significant milestone for patients with AMD," said Luzi von Bidder, president of the ophthalmic business unit of CIBA Vision. "We are confident the FDA will grant approval within the statutory time frame of as late as February 2000."

AMD is the leading cause of adult blindness, and the disease affects at least 10 percent of the U.S. population over the age of 65. Almost 15 percent of all cases of AMD are the wet form, which is characterized by the formation of abnormal leaky blood vessels growing across the central part of the retina, called the macula. Wet AMD typically destroys central vision, which is necessary for reading, driving and recognizing faces. Nearly 90 percent of the severe vision loss associated with AMD occurs in patients with wet-form AMD as a result of retinal scarring.

QLT's Visudyne therapy is a relatively non-invasive, two-step process that targets rapidly growing abnormal blood vessels. The first step is an intravenous infusion of verteporfin, a light-sensitizing agent that binds excess lipoproteins produced by the abnormal blood vessels. The drug is then activated by shining a red laser light in the patient's eyes.

The company presented the 12-month analysis from two 24-month randomized, double-blind, placebo-controlled Phase III trials involving 609 patients. QLT is analyzing the 24-month data, but it won't be available for several months, said Neil Bressler, professor of ophthalmology at Johns Hopkins University and principal investigator for the Phase III studies.

"I think the two-year data is very important," said subcommittee chair Donald Fong, an ophthalmologist with Kaiser Permanente Medical Center in Baldwin Park, Calif. "There doesn't seem to be any issues, but I think it's important to see if there are any long-term changes associated with repeated therapy."

In the studies presented, patients received an infusion of verteporfin or placebo followed by the light treatment. Patients were evaluated every three months by their ophthalmologists, who decided whether they needed additional treatment. The light therapy with verteporfin stabilized or improved vision for 61 percent of patients receiving the drug. Only 46 percent of the placebo-treated group experienced stabilized or improved vision.

In examining which groups attained the most benefit from the therapy, the company found patients with the best outcomes were those with the greatest deterioration of their vision and lesions that could be described as "predominantly classic." A predominantly classic lesion is one in which more than 50 percent of the lesion can be described as being comprised of new leaky blood vessels. Less well-defined wet-form AMD lesions are called occult.

As a result, the company decided to seek a label for the therapy for patients with predominantly classic lesions.

By and large, the most common adverse event was injection site reactions. However, as a photosensitizer, verteporfin, until it is cleared from the body, can cause sunburn-like reactions as a result of exposure to sunlight and bright light. The protocol for the study called for patients to take precaution against sun and bright light exposure for 48 hours. However, because of a couple of adverse events, QLT suggested patients take precautions for three days.

The panel, however, felt the label should advise patients to stay out of the sun for a full week. James Kilpatrick, professor of biostatistics at the Medical College of Virginia in Richmond, said, "I think it should be a week. The cost of this is you get a lot of old people sitting inside watching TV."

The panel also had concerns that physicians may have difficulty diagnosing the classic wet-form lesion, noting the central reading center, where all data were analyzed, identified more cases of leakage following Visudyne therapy compared to the treatment centers. Leakage would create the need for additional therapy.

Bressler noted a treatment effect still was seen, despite the fact some of the physicians missed new leakage.

"We didn't give feedback to ophthalmologists to see if this therapy works in the real world," Bressler said.

The FDA stated there were issues concerning the manufacturing and chemistry of Visudyne; however, the agency told the panel these issues would be dealt with at the agency, not at the hearing.

QLT and CIBA co-developed the drug and have a 50-50 profit sharing deal, with CIBA responsible for the marketing and sales of the drug.

Trading on QLT's stock (NASDAQ:QLTI) was halted Wednesday during the hearing. No shares were traded.