Here's a little more detail from the NY Times. Certainly a disappointing result compared with their earlier trials.
Drug Shows Some Promise Against Vision Loss
By ANDREW POLLACK
Published: November 16, 2003
NAHEIM, Calif., Nov. 15 ? An experimental drug can slow the loss of vision caused by a maddening eye disease that is the leading cause of blindness among the elderly, doctors reported on Saturday.
But in a large trial, the drug did not meaningfully improve vision, they said. That contradicts previously reported results that had sent patients flocking to eye doctors for what they thought might be a miracle cure.
The drug, called Macugen, is intended to treat the wet form of age-related macular degeneration, a disease that can rob people of the ability to read, drive, recognize faces or watch television. More than 200,000 cases of wet macular degeneration are diagnosed each year in the United States.
There is only one drug on the market for macular degeneration, and it is approved for the treatment of only one subtype that represents a minority of cases. Macugen, developed by Eyetech Pharmaceuticals of New York, appeared to work for all types, said Dr. Carmen A. Puliafito, who presented the results of a large clinical trial on Saturday at the American Academy of Ophthalmology meeting here.
"There's a large number of patients for which there really is no approved treatment," Dr. Puliafito, chairman of the Bascom Palmer Eye Institute at the University of Miami, said in an interview. "It really means that Macugen might be the first treatment with the potential to help all" patients with the wet form of macular degeneration.
But some doctors and patients had hoped for even better results. In early, smaller trials, Macugen and another drug like it being developed by Genentech not only slowed loss of vision but significantly improved it. About 26 percent of people who took either Macugen or the Genentech drug, Lucentis, were able to read three or more extra lines on an eye chart. After news reports appeared about people who could suddenly drive or read again, eye doctors reported being besieged by desperate patients trying to obtain the drugs, which were not yet available.
But in the larger trial reported on Saturday, only 6 percent of those getting Macugen had an improvement in vision of three or more lines, compared with 2 percent for those in a control group.
Experts said it is not unusual for results in a large trial with a control group to be worse than those in a small, uncontrolled trial, in which patients being treated might be ones with the best chance of benefiting. Also, the earlier trials measured vision after only three months while the larger trial measured after one year. It is possible that early gains in vision are lost over time.
The new results are from a Phase III trial, typically the last stage before approval. Based on the results, Eyetech and its marketing partner, Pfizer, are expected to apply in the first half of next year for approval, meaning the drug could reach the market by 2005.
The trial, actually two similar trials whose results were combined, had 1,200 patients. About 900 had Macugen injected into the eye every six weeks for a year. The other 300 had an empty syringe without a needle pressed against their eye.
About 30 percent of those getting Macugen suffered a vision loss of three lines or more on the eye chart after one year, less than the 45 percent of the control group that suffered such a vision loss. There were 21 cases of infection, cataracts or retinal detachments in people who got the injections, which Dr. Puliafito called an acceptable risk.
The results were not too different from those of Visudyne, the drug already on the market. In its Phase III trial, about 39 percent of those taking the drug lost three or more lines of vision, compared with 54 percent for the comparison group.
The wet form accounts for only about 10 percent of all cases of age-related macular degeneration but for most of the cases of blindness. The wet form is caused by abnormal blood vessels in the eye that leak blood and damage the macula, the central part of the retina.
Macugen dries up those blood vessels by blocking a protein in the body called vascular endothelial growth factor that promotes blood vessel growth. The same approach is being tried by other companies on cancer, to starve tumors by cutting off their blood supply. Indeed, Genentech's macular degeneration drug is a modified version of its cancer drug, Avastin, which has generated excitement among oncologists.
Genentech, of South San Francisco, is a year or two behind Eyetech in bringing its macular degeneration drug to market. Alcon Inc., of Fort Worth, also has a macular degeneration drug, Retaane, that blocks blood vessels, which it hopes to bring to market by the end of 2005.
Eyetech, a three-year-old company based in Manhattan, has filed to sell its stock to the public for the first time. Pfizer, the world's largest drug company, agreed to pay up to $745 million for the rights to sell the drug, a large sum that companies pay only when they think a drug will become a big seller. Visudyne, developed by QLT Inc., of Vancouver and sold by Novartis, is expected to have sales this year of about $350 million.
Some doctors at the meeting, however, said that it could be hard to interest patients in a treatment that will not improve their eyesight. Still, some said, Macugen represented an advance that could be widely used.
"I'm glad it really worked," said Dr. Joan W. Miller, chairman of ophthalmology at Harvard Medical School, who was an advisor to Eyetech and other companies. "You can always dream that things can be a slam dunk and solve all your problems. We're finding this is a difficult disease to treat."
nytimes.com |
