By Karen Pihl-Carey
Genentech Inc.'s stock declined modestly Friday following news that the company's anti-CD18 antibody failed to meet its primary endpoint in a Phase II trial in heart attack patients.
"The study didn't meet its primary objective, which was improvement in coronary blood flow 90 minutes after administration of rhuMAb CD18 [recombinant humanized anti-CD18 monoclonal antibody fragment] with Activase, and compared to treatment with Activase alone," said Betsy Rosenberg, senior manager of corporate communications at South San Francisco-based Genentech.
The company will present detailed trial results in August during the European Society of Cardiology meeting in Amsterdam, the Netherlands.
Genentech's stock (NYSE:DNA) closed Friday at $132.25, down $5.25.
"It's clearly a disappointment. We've termed it as a modest negative for the company. No one likes to see any drug fail or not provide positive results," said Eric Schmidt, vice president of SG Cowen Securities Corp., of New York. "But this is one of many products in Genentech's pipeline. Genentech has a very strong portfolio of clinical drugs in development. This one was not a major piece of that portfolio at all."
Franklin Berger, an analyst with J.P. Morgan, of New York, agreed. "It really doesn't have any major impact on the company near-term or even over the next two or three years," he said. "It's disappointing to see a potential pipeline failure, but the company has a very rich pipeline, so it's more of a psychological impact."
In preclinical studies, rhuMAb CD18 appeared to reduce the cardiovascular damage that occurs during a myocardial infarction. And Phase I studies in 37 healthy volunteers demonstrated the agent could be safelyadministered and well tolerated in humans, Rosenberg said.
The Phase II study involved 415 patients at 60 centers in the U.S. and Canada. A randomized, double-blind, placebo-controlled, multicenter study, it enrolled heart attack patients who presented within 12 hours of symptom onset and were optimal candidates for reperfusion therapy. They were randomly selected for one of three arms: a high dose of rhuMAb CD18, a low dose of the agent, or a placebo. The patients were administered the dose before or immediately following a bolus of Activase, which was given in a 90-minute infusion.
"We believe the trial was well designed and well executed," Rosenberg told BioWorld Today. "This is preliminary data. We plan to meet with our investigators this summer to evaluate the implications of the data."
Rosenberg added that a preliminary analysis did not indicate any increased risk of adverse events. "We need to fully analyze and understand the results of this trial before deciding whether to develop it for other indications," she said.
Berger said the company may uncover something positive from further analysis of the trial. The company's approach with the antibody is exciting, he said, because of its potential to preserve heart muscle. "This is the first time," he said, "that we've really had a drug that treats the inflammatory component of heart attack."
Schmidt said rhuMAb CD18 still had a long way to go in the acute myocardial infarction (AMI) indication. It would have been launched sometime in 2004 at the earliest. "We would have much preferred the trial to have worked," he said, "but I don't think this changes the fundamental story behind Genentech, which continues to be a strong story."
Activase has been the most widely used thrombolytic over the past decade, Genentech has said. The company received approval for the drug in November 1987 for acute myocardial infarction. It later received approval for acute pulmonary embolism in June 1990 and acute ischemic stroke in June 1996.
Although Genentech's stock dipped Friday, it still closed higher than earlier this month when the FDA approved for marketing the company's thrombolytic agent TNKase (tenecteplase) for AMI. Analysts have said the product, which can be administered in about five seconds and in one dose, has the potential to cannibalize Activase in the AMI indication. (See BioWorld Today, June 6, 2000, p. 1.)