By Jim Shrine
ICOS Corp.'s lead drug, LeukArrest, failed to demonstrate statistical significance in the primary endpoints from a Phase II trial in patients with trauma-induced hemorrhagic shock, sending the company's stock down 20 percent.
While it is the company's lead drug, that is not the lead indication. The humanized antibody designed to inhibit cell-adhesion molecules was taken into a Phase III trial in January in patients with acute ischemic stroke. (See BioWorld Today, Jan. 26, 1999, p. 1.)
An investigator reported Tuesday that the 150-patient Phase II study in hemorrhagic shock failed in its two primary endpoints: reductions in crystalloid (fluids) administered to patients in the first 24 hours; and the extent of multiple organ failure. The trial did show, however, statistically significant inhibition of pulmonary failure and cardiac failure in high-dose (75 milligram) patients.
"We see it much more positively than the Street has," said Lacy Fitzpatrick, associate director of investor relations at ICOS. "We just gave the raw numbers, and hoped people would see the positives in it. There were some benefits to patients."
The company said there was no improvement in 28-day mortality, the number of days spent in intensive care, and the number of days free of mechanical ventilation. There was a suggestion, though, that LeukArrest given at the high dose inhibited the incidence of acute respiratory distress syndrome (ARDS).
Fitzpatrick said the study will help the company as it moves forward into a Phase II/III or Phase III trial in this indication. For example, she said, the endpoint of multiple organ failure may be unreachable but the drug did provide significant benefit for individual organs - the heart and lungs.
Another example of a lesson, she said, was that stabbing victims did not develop ARDS, regardless of whether they were treated with drug or placebo. But the drug did produce an ARDS benefit in patients with blunt trauma and gunshot wounds, since there is more tissue damage in those injuries.
The trial included two drug groups - 75 milligrams and 25 milligrams - and placebo. There was no difference in adverse events among the groups, Fitzpatrick said.
ICOS, of Bothell, Wash., also is developing LeukArrest for myocardial infarction and multiple sclerosis. It is in Phase II trials in both indications. The drug, formerly called Hu23F2G, is designed to block movement of leukocytes from the bloodstream into inflamed tissue. An erectile dysfunction product, IC351, being developed with Indianapolis-based Eli Lilly and Co., is expected to enter Phase III trials in the third quarter, Fitzpatrick said.
The stock fell (NASDAQ:ICOS) fell $9.06 Tuesday to close at $34.937. That price still is significantly higher than it was earlier in the year. On Jan. 26, when ICOS started the Phase III stroke trial, the stock closed at $26.50.