Bat Saliva-Based Stroke Drug Disappoints in Trial
By Ed Edelson
Thursday, December 18, 2008; 12:00 AM
THURSDAY, Dec. 18 (HealthDay News) -- An experimental clot-busting drug derived from the saliva of the vampire bat has failed to reduce stroke damage in a major trial.
But hope for the drug, called desmoteplase, remains alive, experts say, because the study may not have been large enough to provide clear results.
"The sample size was underpowered to detect any benefit," said study co-author Dr. Anthony J. Furlan, chairman of neurology at Case Western Reserve University, in Cleveland. "The simplest answer is that stroke is an extremely heterogeneous condition, and it is difficult to predict what the outcomes will be from a smaller size population."
Two earlier and smaller studies showed a benefit when desmoteplase was given intravenously to reopen brain arteries blocked by clots. But there was no significant difference in outcome in the latest trial, called DIAS-2, between stroke victims given desmoteplase and those who got a placebo, said a report to be published online on Dec. 17 in The Lancet Neurology.
But there remains vigorous debate about the best method to use in selecting those stroke patients who will be treated in the next trial, which is in the planning stage, Furlan added.
Desmoteplase was originally spotted in the saliva of the vampire bat, which uses the chemical to keep its victims' blood flowing freely, so it can suck a full meal.
The drug is contending to replace tissue plasminogen activator (tPA), the only current treatment for ischemic strokes, which are caused by blockage of a blood vessel. Most strokes are ischemic strokes; tPA is given by intravenous injection and works quickly to dissolve clots.
"But tPA must be given within three hours of a stroke, so only a small percentage of patients can get the treatment," Furlan noted. "We hope to triple that window to nine hours with desmoteplase."
But the strategy didn't work in DIAS-2, which included 186 people with strokes. A total of 123 patients received either a high or low dose of desmoteplase, while 63 got a placebo.
The death rate was actually higher for those who got the drug -- 11 percent in the low-dose group and 21 percent in the high-dose group, compared to 6 percent for those given a placebo.
So it's back to the drawing board, the researchers said, and one big question is whether the high-tech methods used to select participants in the trial were too sophisticated to be reliable.
DIAS-2 neurologists used either computerized tomography or magnetic resonance scanning to detect what they formally called "mismatches" -- brain areas that have been affected by the stroke but are not yet dead.
"There is a core area of tissue that is dead," Furlan explained. "Around that area are brain cells that are not yet dead, so they can be saved."
That is the theory, anyway. But it's a theory that some of the neurologists involved with the new drug are questioning.
"The current mismatch model is insufficient to identify those patients who would benefit," Furlan said. "We need a more sophisticated mismatch model."
But another school of thought among neurologists is that a simpler, rather than more complex, method of choosing trial participants might be better.
"There is some controversy about the design of the next trial," Furlan said. "Maybe we can select patients simply by determining whether a major artery is blocked, instead of the mismatch. The main way patients would be enrolled is by looking to see if a major artery is blocked out to nine hours, rather than for mismatch."
No firm start date has been set for DIAS-3, said Furlan, who is on the safety committee for the proposed trial.
The trial was funded by German drug company PAION Deutschland GmbH and U.S.-based Forest Laboratories, which had been working together to develop desmoteplase.
Ischemic stroke and is treatment are explained by the U.S. Library of Medicine. http://www.nlm.nih.gov/medlineplus/ency/article/000726.htm