Strange things were happening to Philip Watts. When he woke in the morning he noticed a spray of brown markings on his pillow, which at first looked like coffee grounds. He soon realized they were caused by blood. Several weeks later, he began to vomit huge amounts of phlegm and that's when the Burnaby, B.C. man, who was then 64, decided he had better go to the doctor. After a series of endoscopies - a tube with a video lens was placed down Watts's esophagus - the diagnosis was disturbing. His doctor, Vancouver gastroenterologist Alan Weiss, told Watts he had an ailment called Barrett's esophagus, a condition caused by prolonged acid reflux. This had altered the cells lining his esophagus, the tube leading from the mouth to the stomach, and biopsies showed pre-malignant change. Patients with Barrett's esophagus are 35 times more likely to develop esophageal cancer.
Dr. Weiss told Watts he had two choices: the first was an operation to remove part of his esophagus - major surgery with a five to seven per cent mortality rate that can affect eating and involves lengthy recuperation. The second option was an experimental drug called Photofrin, which is injected intravenously and then activated by light from a low-power laser beamed on the affected area. Watts opted for Photofrin, developed by a Vancouver company QLT PhotoTherapeutics Inc. "Photofrin is a wonderful, wonderful drug," exclaims Watts, now 67, whose Barrett's esophagus appears completely cured, three years later. "It has allowed me to lead a comfortable life."
But Photofrin, which is now approved in many countries for the treatment of lung and esophageal cancer, is not the only remarkable drug in QLT's arsenal of photodynamic therapies. In recent weeks, the company announced results of a final trial for a drug called Visudyne which seems to have a huge impact on patients with age-related macular degeneration - a condition of the retina that is the leading cause of blindness in people over the age of 50. Over 61 per cent of the patients treated with Visudyne experienced a halt in deterioration or improved vision. News of the Visudyne tests, coupled with the U.S. Food and Drug Administration approval of Photofrin for late-stage lung cancer treatments (it had already been approved for early lung cancer), have sent the shares of QLT skyrocketing - from $18 each on the TSE in mid-September to $60 as of Jan. 22. Analysts say Visudyne is a blockbuster drug with the potential to reach sales of $500-million a year. "We're now in the top 16 of biotech companies in North America," boasts QLT president and chief executive officer, Julia Levy, with reason. "This is not a trivial feat."
Nor did it happen quickly. QLT has been toiling in the biotech field for almost two decades, ever since its founders set up a lab in 1981 over a bakery, next to a primal scream therapist. ("You'd hear the screams every so often," Levy laughingly recalls.) The company was started by some University of British Columbia scientists, including Levy, a microbiologist, who wanted to explore commercial applications of their research. Levy was interested in photosensitive molecules, prompted by the experiences of her two children during summers spent at the family cabin on bucolic Sonora Island, off the British Columbia coast. "The children would be outside playing and sometimes they'd have these slashes on their arms, like they had burned their hands in a hot oven," Levy remembers. "I could never figure it out." She consulted a plant biochemist who told her that a common weed, cow parsley, was a photosensitive plant. "He said I'd probably only see burns on the children if it was a sunny day because it needs a certain amount of light to react in the skin. It's what got me thinking about these kinds of molecules."
Levy, now 64, became fascinated and began to investigate. Meanwhile, a medical researcher at Roswell Park Cancer Institute in Buffalo, N.Y., had developed a light-activated drug, Photofrin, to target tumours. It was being tested by Johnson & Johnson. But in the early 1980s, lasers were costly and difficult to use and Johnson & Johnson decided to abandon Photofrin. At a seminar in Hamilton, Ont., Levy met clinicians who had used the treatment. "One woman physician who was using Photofrin to treat breast cancer said she had been pleased with the therapy and was outraged the drug was being withdrawn," Levy explains. "This struck a chord with me." A year earlier, in 1986, QLT, then known as Quadra Logic Technologies Inc., had gone public on the Vancouver Stock Exchange, and was developing pregnancy kits, while trying to develop its own photosensitive drug. "I thought that if Photofrin was being hung out to dry, maybe we should do something about it," Levy says. Her tiny company joined forces with American Cyanamid of New Jersey to purchase the rights to Photofrin.
QLT began clinical trials to explore the drug's impact on various cancers. Researchers learned that, when injected intravenously, it is absorbed by molecules called lipoproteins, then carried through the blood to the tumour. The fast-growing tumour cells, which need lipoproteins for cell division, absorb more Photofrin than healthy cells. Two days later, once the drug has accumulated in the affected area, a red laser, inserted with an endoscope, beams light to the affected area. The light interacts with the drug to create a molecule called singlet oxygen, which destroys cancerous cells. Photofrin has been approved in the United States, France, Germany, Japan, and the Netherlands for treatment of lung and esophageal cancers. In Canada, it is still awaiting federal government approval.
The major drawback to Photofrin is that a person receiving it must avoid sunlight for up to six weeks after. "I was walking around with gloves on, wearing a big sombrero," Watts recalls. And the treatment has the largest impact on cancer patients in the early stages, before the tumorous cells have had an opportunity to penetrate deeply, cautions Dr. Weiss, who is now testing Photofrin on patients through the B.C. Cancer Agency. In later cancers it has more of a palliative effect - shrinking rather than eliminating tumours. It also does not work on cancer that has spread throughout the body. But, Dr. Weiss adds, "I feel very excited about it. I think it will be a fantastic treatment."
Photofrin, however, has never made much money for QLT. "The cancer treatment market is very fragmented for each type of cancer and each stage of cancer," says biotech analyst Ann Dulhanty of Dundee Securities Corp. in Toronto. "So the market tends to be quite small." But the opportunities for Visudyne, on the other hand, are enormous. Over 500,000 people around the world, each year, become blind as a result of macular degeneration. "As people get older the layers of the retina get thinner and if they get very thin, new blood vessels form and they start leaking," Levy explains. The leaky blood vessels damage the macula, or area of the eye responsible for central vision. The Visudyne trials show that "for the first time there is the possibility of an approved drug to treat this disease for which there is no cure," says analyst Ezra Lwowski of Yorkton Securities Inc. in Toronto.
That's why the drug has put QLT on the map, sent its stock soaring and left the clinical community agog. "In the whole history of biotech companies there have been four drugs that have been approved and have $500 million in sales," says Christine Charette, biotech analyst at Nesbitt Burns in Toronto. "This will be the fifth." She explains that of 300 biotech companies operating in North America, only nine are profitable. But that should change for QLT by 2000, Lwowski predicts. He anticipates QLT will achieve revenues of about $103.8 million by 2001, versus $7.7-million for 1998. The company, which has yet to report a profit, should net $38.7-million by 2001. Dulhanty notes QLT and its partner CIBA Vision Corp. of Duluth, Ga. are two years ahead of their competitors in the search for a macular degeneration treatment and she anticipates quick approval by the FDA.
While Levy is pleased by her company's promise, there is also a personal note to her satisfaction. Her mother, Dorothy Coppens, who died two years ago at 94, became blind from age-related macular degeneration. "When my mother was diagnosed, it was the first time I had ever heard of it," Levy says. "It hit me like a ton of bricks." Her mother's predicament led to Levy's exploration for a photodynamic therapy to treat blindness. The drug she helped develop, benzoporphyrin derivative, now called Visudyne, seemed to be the answer.
The treatment has received accolades from medical researchers. In early 1996, Dr. Webb Wilson, an opthamologist who lives in Santa Cruz County, California, began to notice his vision was distorted: "Straight lines were crooked, door jambs looked wobbly." Being an eye specialist, he immediately recognized the problem. He consulted colleagues who told him of the Visudyne trials. "I went from about 20/60 vision to 20/20 in 24 hours," he says. "To say it was dramatic is putting it mildly." Unlike Photofrin, light sensitivity dissipates within 24 hours, so there was no need for a sombrero or gloves. Unfortunately, the 70-year-old doctor lost vision in his right eye, which had developed scar tissue and couldn't respond to Visudyne. Still, he can watch his five grandchildren grow. "I am very, very grateful," he says.
After years of struggling - with share prices bouncing up and down, a revolving door of CEOs, and paltry revenues at QLT - the firm hopes Visudyne is the key to success. "It has given us huge confidence," Levy says. The company will make big money and so will the CEO - on paper she is now worth over $20-million because of stock market excitement. Photodynamic therapy may have dozens of other applications, Levy says, including treating auto-immune diseases such as psoriasis and arthritis. Analyst Lwowski says much of the credit for QLT's new recognition should go to Levy, who became president in 1996. "She was always known as a good scientist but certainly there was nothing in her background to suggest she could run a company," he says. "What she has done is pretty remarkable." QLT's results so far hold out the promise to repair the eyesight of millions and to restore the health of those such as Philip Watts, who now chops wood, eats curry, and leads a cancer-free life.
Maclean's February 1, 1999