WASHINGTON _ In a few short weeks, results from Chiron Corp.'s900-patient Phase III clinical trial of the sepsis drug T-88 will beknown within the company. Chiron has managed to lower expectationsfor the drug on Wall Street to just about zero: nary an analyst has builtT-88 revenues into earnings projections.And T-88 has plodded through three years of patient accrual in itspivotal trial with little fanfare. But results from this trial will test animportant treatment hypothesis for this exasperatingly complex disease.The Emeryville, Calif.-based company has already begun focus groupresearch to determine what potential customers believe constitutes aviable product for sepsis.Individuals identifying themselves as marketing staff from Chiron havebeen calling clinicians and offering $100 for a half-hour's worth ofinput. The Chiron employees have been asking a series of questionsapparently crafted to gauge how varying levels of clinical efficacywould be viewed. A typical line of questioning reported by sourceswas: How would you view a sepsis drug which achieved a 35 percentreduction in mortality? A 25 percent reduction? A 15 percentreduction?"We're trying to know the standard for defining a viable product so thatwhen we know the results from the T-88 trial, we'll be able to judge theproduct better from a marketing standpoint," said Larry Kurtz, Chiron'svice president of corporate communications. Kurtz added that suchsurveys were not "atypical."The company will use information from respondents to help themdecide whether to kill the T-88 product or to file a product licensingapplication (PLA) with FDA, according to Kurtz. "There's a differencebetween a product that can be approved and a product that can bemarketed," said Kurtz.History suggests that, marketing research aside, the FDA wants newsepsis products to demonstrate a statistically significant reduction inmortality in a prospectively defined group of patients. The agency hasnot yet approved any product for sepsis since not a single one hascleared this hurdle.Sepsis is a cascade of immune system reactions triggered by infectionfrom invading bacteria (gram-negative or gram-positive) or fungi. It isa syndrome which can lead to organ failure and death at rates estimatedto between 30 and 70 percent. The mortality rate for biotechnologyproducts attempting to treat sepsis has been 100 percent.T-88, a dark horse candidate in the race to capture the potentially hugesepsis market, is a monoclonal antibody designed to target and bind toenterobacterial common antigen (ECA), a microbial antigen commonto many gram-negative bacteria. Although this may sound eerilyfamiliar to investors with bitter memories of high-profile anti-endotoxin antibody failures such as Centocor Inc.'s HA-1A and XomaCorp.'s E5, T-88 may prove truly different.The anti-endotoxin and T-88 approaches are similar in that both takeaim at portions of gram-negative bacteria: anti-endotoxin antibodiestarget a lipid-sugar common to all gram-negative bacteria while T-88targets a protein found on many (but not all) gram-negative bacteria.However, anti-endotoxin antibodies were not designed to kill bacteria,but rather to bind to a single bacterial by-product, endotoxin, and clearit from the blood.T-88 was designed to bind to bacteria and then harness the naturalimmune processes of the body to kill and clear the bacterial invaders.That process _ known as opsonization _ is a process wherebyimmune system scavenger cells called neutrophils are alerted to anddevour foreign matter.The anti-endotoxin approach is based on the premise that binding andremoving endotoxin from a patient's circulation is the key to curinggram-negative sepsis. T-88 is based upon the premise that killing thebacteria and removing it from the body is key, a premise closer to thatunderlying the use of antibiotics.One question facing T-88 is whether or not the drug will work betterthan antibiotics, one of the standard current therapies for sepsis. Whileantibiotics simply kill bacteria, T-88 may prove to better kill and clearbacteria from the system.Making predictions about whether or not new sepsis drugs will work issomething that most stock analysts have ceased to engage in.Biotechnology analyst David Stone, from Cowen & Co., said hebelieves that positive results from the T-88 trial could function as a"wake-up call" to Chiron investors who have focused too narrowly onBetaseron, the company's drug for multiple sclerosis that received FDAapproval late last year.Greg Brown, an analyst with Vector Securities Interntational Inc., inDeerfield, Ill., said that even if T-88 is positive, no one may believe it."If it works, the data will be scrubbed over with a fine-toothed comb,"he told BioWorld. "It would be a big surprise. Though a surprise isalways nice in a bad market, I wish this drug were for a differentdisease."
-- Lisa Piercey Washington Editor
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