By Mary Welch

QLT PhotoTherapeutics Inc. and Ciba Vision Corp. submitted a new drug application (NDA) for Visudyne, a light-activated therapy for the treatment of wet age-related macular degeneration (AMD).

"We met our milestone in an appropriate time frame and we're pleased to do that," said Julia Levy, president and CEO of QLT. "It's obviously a major thing. It's the most important event in the history of the company as we take it one step at a time in terms of achievements."

"This is a company-changing event," said Joe Dougherty, an analyst with Warburg, Dillon, Read LLC, of New York. "They have finally found the right indication, the right trial and the right partner. This could really make a difference. There's such an urgent need in this indication."

Kevin Tang, senior biotechnology analyst with Deutsche Bank Alex.Brown Inc. in New York, estimated Visudyne could ring up sales of $262 million in 2001, $450 million in 2002 and $546 million in 2003.

"Visudyne has the potential to drive QLT into substantial profitability beginning in 2001," he said. "We are projecting earnings per share of $1.24 in 2001, $2.75 in 2002 and $3.48 in 2003 based on our projected sales of Visudyne. In fact, we see QLT as one of only a small handful of companies positioned to enter the top tier of the biotechnology industry over the next few years."

For his part, Dougherty is even more effusive. "This could easily be a billion dollar product," he said. "It looks like this will be the dominant player in the market at this time. In fact, I've just revised my numbers. I think it is likely that QLT will be profitable for the whole year next year."

In the second quarter of 1999, QLT posted a net loss of $4.2 million (C$6 million), or 14 cents per share, on revenues of $500,000.

Levy explained Visudyne's projected sales figures. "There's over 200,000 new cases of AMD in North America each year, 500,000 worldwide, and it'll increase as the population ages," she said. "The treatment cost will be about $1,200 and it takes a total of five to six treatments over two years. It's a huge product and there's no existing therapy except for laser photocoagulation, which applies to only a small subset of the population. There is a huge upside for revenue."

QLT, of Vancouver, British Columbia, signed a co-development deal with Atlanta-based Ciba Vision Corp., the eye care unit of Novartis AG, of Basel, Switzerland, under which profits will be split 50-50. "Ciba paid 60 percent of the development costs and we paid 40 percent," Levy said. "That was because we had already filed for an IND (investigational new drug) application to start Phase I, so we were pretty far along at that point. We will share equally the marketing costs, although Ciba is responsible for marketing."

The filing's specific indication is for the treatment of AMD in patients with predominately classic subfoveal choroidal neovascularization, which is the most aggressive cause of vision loss associated with the disease.

The filing is based on 12-month data from two 24-month randomized, double-masked, placebo-controlled Phase III trials known as the TAP (Treatment of AMD with Photodynamic therapy) Investigation. Some 609 patients were enrolled at 22 centers in North America and Europe. (See BioWorld Today, Jan. 6, 1999, p. 1.)

At the 12-month period, statistically significant results were achieved on the combined data in the main endpoint as well as secondary endpoints. Of the 243 patients with predominantly classic lesions, 67 percent of those treated with Visudyne therapy had their vision stabilized or improved, compared to 39 percent taking the placebo.

"It should be noted that 16 percent showed an improvement in vision in one or more lines on a standard eye chart vs. seven percent for those receiving the placebo," Levy said. "We had seen evidence of this improvement in Phase I/II trials at three months and we are very pleased to see it at 12 months."

The secondary endpoints, which included contrast sensitivity and lesion growth, also showed that the Visudyne patients experienced significant improvement over those taking the placebo. There were no serious side effects.

The Visudyne treatment consists of a two-part therapy. The drug verteporfin is injected intravenously into the patient's arm and selectively accumulates in the eye's abnormal blood vessels. A red non-thermal laser is shined into the patient's eye to activate the drug. Verteporfin then selectively affects the blood vessels, stopping their growth and corresponding vision loss.

There are two forms of AMD: wet and dry. Characterized by yellow depositions on the retina, the dry form (atrophic) is the more common and can lead to the severe "wet" form. Wet form (neovasular) AMD accounts for about 15 percent of all cases, but leads to 90 percent of severe vision loss. The wet form is caused by the growth of abnormal leaky blood vessels that seep fluid and blood into the tissues at the back of the eye, causing a blister to form in the retina, leading to scarring and vision loss.

The companies filed for marketing approval in Europe Aug. 9 and expect a decision in 12 to 18 months, Levy said. A filing in Canada is expected soon. If the product receives FDA priority review, it could be reviewed within six months and launched in the first quarter of 2000.

The company's two 24-month Phase III trials should end next month with the final patients getting their last treatment. Two Phase IIIb trial are under way for occult AMD, or early-stage AMD, and pathologic myopia. Pathologic myopia is a similar but distinct condition resulting from progressive near-sightedness. The trials, called Verteporfin In Photodynamic therapy (VIP), complement the TAP trials. An expanded access program will also start next month at more than 150 sites in North America and more than 100 in Europe.

"We have three areas of potential label expansion next year - occult AMD, pathologic myopia and 24-month, because we'll have the data by then," Levy said.

Said Dougherty, "We look forward to a smooth panel review by year's end, and a rapid launch. Obviously, we expect everything to go well."

QLT's stock (NASDAQ:QLTI) closed Monday at $79.062, up 50 cents.