By Randall Osborne

Genentech Inc. said a data safety monitoring board (DSMB) recommended stopping its Phase III study of tPA administered three to five hours after a stroke because no significant clinical benefit could be shown.

First sold in the late 1980s for treatment of acute heart attack, Activase (marketed as Alteplase outside the U.S.) also is approved for administration within three hours of the onset of acute ischemic stroke. The serine protease enzyme breaks up clots to restore blood flow.

Genentech, with marketing partner Boehringer Ingelheim GmbH, has been trying to show good results with tPA beyond the three-hour window. Those efforts will stop, said Betsy Rosenberg, spokeswoman for South San Francisco-based Genentech.

"This is it," Rosenberg said. Although data were not expected to be reported from the U.S. trial — which studied patients three to five hours into symptoms — until next year or the year after, enough was on hand for the DSMB to examine, Rosenberg said.

Last week, Boehringer, of Ingelheim, Germany, said its European Cooperative Acute Stroke Study II (ECASS II) failed to show statistically significant clinical benefit in preliminary findings. (See BioWorld Today, July 13, 1998, p. 1.)

In that trial, the safety profile was comparable to placebo and the overall mortality was lower compared with earlier stroke trials, but patients measured in the ECASS II trial's primary endpoint — minimal functional deficit or no deficit — did not reach statistical significance compared with placebo.

ECASS II was designed to study the drug's effect in patients presenting for treatment as long as six hours from symptom onset.

"[The DSMB] does interim analysis when they feel there might be a reason to take a look at it," Rosenberg told BioWorld Today. Since the ECASS II trial results were negative, the board checked out the U.S. study's data.

"You can't really compare the [U.S. trial and ECASS II]," Rosenberg added. "There were different criteria, but the time window was the biggest difference."

She said Genentech will keep working with the medical community and the public, to reaffirm stroke as an emergency deserving of quick response.

Activase, the only FDA approved drug for stroke, was given the agency's marketing go-ahead in June 1996. It had been approved for pulmonary embolism in 1990.

Genentech's stock (NYSE:GNE) closed Monday at $68.625, up $0.50. *

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