The Wall Street Journal - November 9, 2004
Rhonda L. Rundle at rhonda.rundle@wsj.com

Macular degeneration affects roughly a third of people over age 75 and is the leading cause of blindness in the elderly. With the aging of the U.S. population, doctors are warning of a looming epidemic. By 2025, more than 11 million Americans will suffer from the condition, according to estimates.

The most common, or "dry," form of the disease is characterized by an accumulation of yellowish deposits in the eye, a residue of broken down light-sensitive cells. Patients may notice their vision is hazier, colors are washed out and they need brighter light when they're reading. But only about 10% of such patients progress to the more severe "wet" form of the disease that can lead to blindness.

Current treatments, as well as those on the way, are generally aimed against the wet form. The leakage of fluid from renegade blood vessels in the eye gradually destroys central vision. Lasers began to be used in the 1980s to fry the bad vessels, but only when they are outside the central visual field. Four years ago, the drug Visudyne was approved with photodynamic therapy. Visudyne, developed by QLT Inc. of Canada, slows progression of the disease in some patients.

At the American Academy of Ophthalmology's annual meeting in New Orleans last month, eye doctors were buzzing about Lucentis, an experimental drug developed by Genentech Inc. of South San Francisco, Calif. Lucentis is designed to block a protein that plays a critical role in the formation of new blood vessels.

Based on results of small human tests and doctors' anecdotal reports, Lucentis holds out the promise of improving vision rather than merely slowing its deterioration. "Just seeing my patients, I know this stuff is working," says one of the drug's investigators, Peter Kaiser, director of clinical research at the Cleveland Clinic's Cole Eye Institute.

Dr. Kaiser cautions that his "gut feeling" about Lucentis will have to be confirmed by more testing. Another caveat: Other eye drugs that showed promise in small tests, including two that are much farther along in the pipeline, Macugen and Retaane, haven't lived up to the initial enthusiasm.

Macugen is awaiting Food and Drug Administration approval, which could come next month. Much like Lucentis, Macugen blocks a protein that is important for the growth of new blood vessels. "The main effect is in preserving vision rather than reversing loss," says Anthony P. Adamis, chief scientific officer for the drug's developer, Eyetech Pharmaceuticals Inc. of New York.

In a trial of over 1,100 patients, those who didn't receive the drug lost twice as much vision as those who got Macugen. "What we saw was a broad-based efficacy, irrespective of the size and subtype" of the disease, Dr. Adamis says. Visudyne, by contrast, has FDA approval to treat a particular type of wet macular degeneration found in up to a quarter of patients. Many doctors are using it to treat the other 75%, however, because it's the only drug treatment on the market.

Macugen "isn't an advance as much as it is another treatment we can add to our armamentarium," says Dr. Kaiser. For most lesions, he said, Macugen has similar results to Visudyne with photodynamic therapy, although "for larger lesions Macugen may be better."

Visudyne is injected into a vein in the arm and accumulates in abnormal blood vessels in the eye. It is activated when a laser beam is shone into the patient's eye. Patients are typically treated several times at intervals of at least three months.

The introduction of Eyetech's Macugen will ignite a battle between two pharmaceutical giants. Eyetech's marketing partner, Pfizer Inc., will go up against Novartis AG, which sells QLT's Visudyne. World-wide sales of Visudyne this year are expected to be about $450 million, which "is testimony more to the desperate need for new treatment options" rather than the drug's effectiveness, says Larry Haimovitch, a medical technology consultant in Mill Valley, Calif. Analysts are forecasting peak sales for Macugen of more than $1 billion.

Prospects for a third drug, Alcon Inc.'s Retaane, plunged last month after the disclosure of disappointing results from a pivotal test. However, Alcon says there was a tendency for the drug to leak out of patients' eyes before it could do its job. The Swiss company has developed a device to correct the problem and is moving ahead with an FDA application by the end of the year. Macugen and Lucentis are injected directly into a patient's numbed eyeball, while Retaane is injected into the side of the eye.

While many specialists are skeptical that Retaane will be approved, Alcon remains hopeful that the FDA will give it a green light because "macular degeneration is a serious disease and there aren't a lot of treatments out there," says Doug MacHatton, a company spokesman.

Many doctors said the brightest hope for macular degeneration treatment may be drug combinations similar to the cocktails that fight cancer and HIV. "We're making gains on a disease that is pretty difficult to treat, but the gains can never come fast enough for doctors and patients," said Donald J. D'Amico, professor of ophthalmology at Harvard Medical School in Boston.

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