Researchers split on whether it slowed disease progression in trial
WEDNESDAY, Sept. 23 (HealthDay News) -- A study to see whether a new drug can stop the progression of Parkinson's disease has produced results that have drawn sharply differing reactions from neurologists.
The drug, rasagiline (Azilect), was approved in 2006 by the U.S. Food and Drug Administration on the basis of studies showing that it reduced Parkinson's symptoms such as trembling and slowed motion. The new study, reported in the Sept. 24 issue of the New England Journal of Medicine, was designed to determine whether the drug also acts on the underlying nerve deterioration that causes the disease.
"In our heart, what we are hoping for is neuroprotection," said study author Dr. C. Warren Olanow, a professor of neurology and neuroscience at Mount Sinai School of Medicine, in New York City.
To distinguish the effect on symptoms from the hoped-for effect on the underlying disease, "we used a totally new study design, to see if it is disease-modifying," Olanow explained.
The study enlisted 1,176 people with previously untreated Parkinson's disease who were seen at medical centers around the world. At the start, half took daily doses of either 1 milligram or 2 milligrams of rasagiline for 36 weeks, while the other half took a placebo. After that, all the participants took either 1 milligram or 2 milligrams of rasagiline for another 36 weeks.
A complex system to measure the treatment effects showed an apparent improvement in the participants who took the 1-milligram doses but not in those taking the 2-milligram doses.
"It did something to affect the course of the disease," Olanow said. "We don't know why, but we are entitled to speculate."
His speculation is based on a detailed study of the 25 percent of participants who showed the greatest benefit. "What I think is right is that the higher dose had a greater effect on symptoms than the lower dose, so that masked our ability to detect its effect on disease progression," Olanow said. "We thought that this floor effect was why we couldn't see a difference."
Olanow was enthusiastic about the results. "This doesn't prove unequivocally that it [rasagiline] is neuroprotective, but there is no other rational explanation for the results," he said. "This is good news for Parkinson's patients."
Asked if he would prescribe the drug for that reason, Olanow said, "Yes, I would personally prescribe it."
A much more skeptical response came from Dr. William J. Weiner, chair of neurology at the University of Maryland, who took part in the study.
"The authors were very careful in the paper not to indicate that they had shown neuroprotection," Weiner said. "The tone of the article itself is moderate."
The methods used to determine trial results need scrutiny, he said. "They used a lot of very fancy mathematical models, some of which had not been used before," Weiner said. "Most neurologists wouldn't understand the mathematical models they used. Research neurologists don't deal with equations about the slope of curves."
And the end results were not impressive, he maintained. "The difference reported in the study is less than two points on a scale that has 150 points," Weiner said.
The reason why the lower dose worked, and the higher one didn't? "It simply could be luck," he said.
While rasagiline can provide benefits in reducing symptoms of early Parkinson's disease, Weiner said he was worried that "patients will be given what I believe to be false hopes" by the new study.
"It has mild symptomatic effects, but I do not prescribe this drug for neuroprotection and this study doesn't convince me to do that," Weiner said.
Several of the study authors have received consulting or lecturing fees from pharmaceutical companies, including Teva, the maker of Azilect.
Learn about Parkinson's disease from the U.S. National Institute of Neurological Disorders and Stroke (http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htm ).
SOURCES: C. Warren Olanow, M.D., professor, neurology and neuroscience, Mount Sinai School of Medicine, New York City; William J. Weiner, M.D., professor and chair, neurology, University of Maryland, Baltimore; Sept. 24, 2009, New England Journal of Medicine