LOS ANGELES (Reuters) - More than a decade after the launch of clot-buster Activase, the Genentech Inc drug remains the only option for stroke victims despite high-profile research aimed at improving the odds of recovery from the No. 3 cause of death in the United States.
Since most stroke patients are unable to quickly recognize their symptoms, just a small percentage end up being treated with Activase, an intravenous drug approved for use only within three hours of the onset of a stroke.
Drug companies have sought to widen that treatment window and develop medicines that would protect the brain from damage caused by a stroke, but the field is littered with failures.
Last August, drugmaker Forest Laboratories pulled out of a partnership to develop clot-buster desmoteplase after a late-stage trial failed to show that the drug, which is derived from vampire bat saliva, worked better than a placebo.
Shares of Paion AG, the German biotechnology company that discovered desmoteplase, fell 64 percent after the trial results were announced. But Paion and partner Lundbeck A/S are pushing on with another trial looking at a treatment window of up to nine hours.
Nuvelo Inc on Monday ended development of its experimental stroke drug alfimiprase after it failed to demonstrate effectiveness in unblocking catheters, sending the company’s shares down 46 percent.
The biggest risk of clot-dissolving drugs is hemorrhage and they can’t be used in patients with evidence of recent bleeding, head trauma, high blood pressure or other risk factors. Even with those restrictions, about 6 percent of patients treated with Activase suffer brain hemorrhage.
“There is a lot of skepticism about any stroke drug due to the recent failures ... all this has frightened the large pharma companies,” said Paul Freiman, chief executive of Neurobiological Technologies Inc, which expects interim results late this year from pivotal trials of its experimental stroke drug Viprinex.
The company, which has seen its shares fall about 85 percent since last March, aims to show that Viprinex, derived from the venom of the Malaysian pit viper, can be used to dissolve blood clots for as long as six hours after a stroke, but with less risk of bleeding than Activase.
Studies have also suggested that the treatment window for Activase could be widened for at least some patients.
“A number of drugs are trying to get out to a six-hour window. That’s where the field is going,” said Dr. Anthony Furlan, chairman of neurology at University Hospitals Case Medical Center in Cleveland and principal investigator for clinical trials of desmoteplase.
Acute ischemic stroke occurs when a blood vessel that carries oxygen and nutrients to the brain is clogged by a blood clot or other obstruction.
These types of stroke, which account for the vast majority of the more than 700,000 strokes suffered by Americans each year, are the leading cause of disability and the third leading cause of death in the United States.
Genentech’s Activase, also known as alteplase, is designed to activate naturally-occurring plasminogen, starting a biochemical reaction that dissolves the blood clot and restores blood flow to the brain. Desmoteplase works in a similar manner.
Viprinex has a different mechanism of action. It is an enzyme that reduces levels of fibrinogen, a protein involved in blood clotting, making blood less viscous.
“It breaks up the clot in a more gentle way ... and it stays in the blood to prevent re-clotting,” Freiman said.
Viprinex, known generically as ancrod, was originally developed by a company since acquired by Abbott Laboratories, which shelved the drug after a pivotal trial showed that it raised the risk of brain bleeding.
But earlier trials used a less-than-ideal dosing regimen, and infused the drug over too many days, which caused fibrinogen levels to go to low, for too long, Freiman said. “We have changed the treatment paradigm ... in our estimation a two-to-three hour intravenous drip at a rather high dose will give a better effect,” he said.
Freiman said the new trial regimen is anticipated to reduce bleeding rates by as much as 50 percent. “We feel that the drug’s effect in the first 12 hours following a stroke is critical,” the CEO said. Results of the next periodic safety review of the Viprinex trials are expected in April.
The studies use conventional imaging to exclude from treatment patients who have already suffered intracranial bleeding, but Dr. Furlan questioned the feasibility of a trial that does not measure whether a patient has “tissue at risk” and would therefore benefit from clot-busting treatment.
Without such comparative imaging, the risk of hemorrhage is high, he said. “It’s very clear that you can’t just treat everybody after three hours ... as time goes on fewer will benefit,” Dr. Furlan added.
Reporting by Deena Beasley; Editing by Tim Dobbyn