Drug sparks controversy

Joel Sawyer

When the Food and Drug Administration approved the blood clot-dissolving drug Activase for the emergency treatment of stroke victims earlier this month, new hope was offered to the nearly 400,000 Americans each year who suffer strokes caused by blood clots in the brain.
But University neurologist Dr. Arthur Klassen thinks celebrating the drug’s approval may be premature.
Activase is a “wonderful treatment that will render people virtually normal or without any disability at the end of the treatment,” he said. “But at the same time, there will be some people who will get worse and die because of the treatment.” For that reason, Klassen said, the drug is risky and is a “two-edged sword.”
Klassen’s main concern with Activase is that the drug can cause bleeding in the brain. After the drug dissolves a blood clot, tiny blood vessels, weakened by a lack of blood flow, are at risk of bursting. The broken blood vessels release blood into the brain. This can cause brain damage, paralysis and death.
These possible effects of Activase use are worse than the paralysis and brain damage typically suffered by stroke victims, Klassen said.
According to the National Institutes of Health, stroke is the third leading cause of death in the country after heart disease and cancer, killing about 150,000 Americans each year. Eighty percent of all strokes are caused by a blood clot that reduces blood flow to the brain. The remaining 20 percent are caused by bursting blood vessels in the brain. The cost of strokes to the nation is an estimated $30 billion each year.
Norman Oliver, a spokesman for the National Institute of Neurological Disorders and Stroke, said in response to Klassen’s criticism, “In terms of the devastation stroke causes, the risk pales in comparison to the benefit you’re doing.” After all, he said, in the clinical trials the drug helped one-third of those who used it, while only about 7 percent of patients experienced bleeding that worsened the effect of the stroke.
Activase, which has been used to dissolve blood clots in heart attack victims for nearly 10 years, was approved by the FDA to treat strokes after a five-year clinical study organized and funded by the National Institute of Neurological Disorders and Stroke.
FDA guidelines say the drug must be used within three hours of the stroke and must be administered by trained personnel. “Not just anyone should be using it cavalierly,” Oliver said.
The speed with which the FDA approved Activase is also a concern for Klassen. He said the FDA’s approval of Activase was unique because only one clinical trial had tested the drug’s effectiveness. The FDA normally relies on the results of at least two studies before approving a drug.
John Leland, a spokesman for Genentech, Activase’s manufacturer, said the FDA acted correctly in their swift approval. “Obviously, the trial itself was rigorously scrutinized by the FDA,” he said. “They were very impressed.”
Oliver agreed with Leland. “Why shouldn’t they approve it rapidly?” he said. “The FDA was faced with a first-class study.” Oliver also noted that the clinical trial was actually two studies, with the first study rolling into the second without investigators knowing the results of the first study.
Klassen said he will begin a new clinical trial of the drug in conjunction with more than 100 medical centers around the country. The new trials will test Activase’s effectiveness three to five hours after strokes occur. Klassen said he hopes the new trials will help determine which patients are most suitable for use of the drug. “The trouble is that we don’t know how to pick those (patients) right now,” he said.
At the same time, Klassen said he is also experimenting with other methods to treat stroke victims. He said he was in the early stages of testing neuronal protective agents that keep cells alive until blood flow is naturally restored to the brain as a blood clot dissolves on its own.