Septic shock continues to be an elusive disease target forbiotechnology drug developers.

So far, it's already gotten the better of biotechnology companiesCentocor Inc. and Xoma Corp., with their anti-endotoxinantibodies, and Synergen Inc., with its anti-cytokine(interleukin-1 receptor antagonist) drug. More recently,Immunex Corp. reported that its soluble tumor necrosis factor(TNF) receptor provided no clinical benefit in a Phase II study.

Yet another potential therapy, a murine monoclonal antibody toTNF discovered by Chiron Corp. (NASDAQ:CHIR) and licensed toBayer AG for clinical development, has proved to be onlymarginally efficacious. It appears to work, but not in astatistically relevant manner.

"The results showed a strong trend toward a reduced mortalityin septic shock patients," explained George Scangos, head ofMiles' newly formed biotechnology business unit.

Data from the multicenter Phase III U.S. clinical trial of thisantibody, BAY X1351, were presented at the 33rd InterscienceConference on Antimicrobial Agents and Chemotherapy(ICAAC) by researchers associated with the German companyand its U.S. health-care company Miles Inc. of West Haven,Conn.

In the trial, patients with sepsis were prospectively stratifiedby shock vs. non-shock and then randomized to receive a singleintravenous dose -- either 7.5 or 15 milligrams per kilogram --of the anti-TNF antibody. Patients were monitored for clinicaland laboratory measures of efficacy and safety. Survival ornon-survival was determined over the 28-day study period.

The clinicians performed an interim analysis after the first 800patients were enrolled in the trial. Based only on survival data,they concluded that "if the study continued as initiallydesigned, there would be insufficient power to support efficacyof TNF monoclonal antibody at either dose for all sepsispatients."

While there was a trend among shock patients toward efficacywith lower mortality rates at both doses, among non-shockpatients, "TNF monoclonal antibody did not appear beneficial."

Detailed data from the trial will be submitted for publication inthe near future, according to Scangos.

Miles intends to initiate another North American Phase IIIclinical trial in sepsis patients later this year, Scangos toldBioWorld. That trial will be designed to "take into account whatwas learned from the first Phase III," he added.

-- Jennifer Van Brunt Senior Editor

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