By Karen Pihl-Carey

Synsorb Biotech Inc. watched its stock fall 28 percent on Thursday following news that Synsorb Pk did not meet its primary objective of preventing hemolytic uremic syndrome (HUS) in children with Escherichia coli infections within five days of the onset of symptoms.

The drug, however, did show statistical significance in preventing HUS if administered within two days of the onset of symptoms.

"This is a very shiny, silver lining in what many are perceiving to be a cloud," said David Cox, president and CEO of Calgary, Alberta-based Synsorb. "We have huge amounts of safety data on this drug now, and the drug is incredibly safe."

Synsorb's stock (NASDAQ:SYBB) closed Thursday at $2.875, down $1.125, or 28 percent.

In the Phase III trial of 526 children, the interim analysis showed about one-third of patients were treated within two days of the onset of their symptoms. The subgroup of 152 patients demonstrated a statistically significant (p<.05) lower rate of HUS for Synsorb Pk (7 percent) compared to placebo (17 percent). When compared to placebo, Synsorb PK reduced the risk of developing HUS by 59 percent.

"When kids are allowed to continue into days three and four with the onset of symptoms, then our drug is not able to help them," Cox told BioWorld Today. "That's what we've discovered. But, if we can catch the disease between days one and two of symptom onset," Synsorb Pk shows statistically significant results.

A Data and Safety Monitoring Committee comprised of third-party external reviewers confirmed the safety of Synsorb Pk and have concluded that there are no ethical or scientific reasons for discontinuing the trial, the company said. Synsorb, however, does not plan to continue recruiting patients until after discussing the recent data with regulatory authorities.

"The next step is consultation with the regulatory authorities," Cox said. "We will be going to the FDA and Health Canada, probably to Health Canada first, to present results and see where we go from here."

The company may decide to stop the trial completely and start a new one, or to restart the current trial with a different design, he said. If Synsorb needs to recruit more patients into the trial, it may seek third-party financial support.

It also is possible, Cox said, that regulatory authorities would support the filing of a new drug application (NDA) based on the data already gathered.

"We're dealing with a disease that kills children [for] which there is no treatment," he said. "We have a drug that has statistically significant efficacy and is safe if put on the kids right away."

The company began the Phase III trial of Synsorb Pk in 1996. It was expected to be completed by now, but patient accrual took longer than anticipated.

About 250,000 children in North America, Europe and Japan are at risk of developing HUS, a severe and sometimes fatal kidney disease. Developing HUS can lead to a lifetime of dialysis and other serious complications. Patients infected with E. coli often go on to develop HUS. Because there is no treatment for the life-threatening disease, Synsorb Pk has fast-track status.

Verotoxigenic E. coli is a foodborne infectious disease that causes about 110,000 infections each year in the U.S. Sources of the infection include contaminated meat, fruit and vegetables, unpasteurized juice and milk, contaminated groundwater, contaminated swimming pool water, and direct contact with infected people or animals.

In May, upon approval from Canadian authorities, Synsorb shipped emergency supplies of Synsorb Pk to hospitals in the Walkerton, Ontario, region in response to the E. coli outbreak in the area.

The company has another product candidate in a Phase III trial. In April, it began enrolling its first patients in a pivotal trial of Synsorb Cd, which is designed to prevent recurrent Clostridium difficile-associated diarrhea. (See BioWorld Today, April 4, 2000, p. 1.)

Both Synsorb Pk and Synsorb Cd are licensed in Canada to Paladin Labs Inc., of Montreal. Synsorb Pk also is partnered in Japan with Takeda Chemical Industries Ltd., of Osaka, Japan, and in the Netherlands, Belgium and Luxembourg with Tramedico International BV.