By Brady Huggett

ICOS Corp. began patient enrollment in a pivotal Phase III trial in severe sepsis with its partnered product, Pafase, and is now standing on the spot where so many previous biotechnology companies have stood and failed.

The trial is designed to enroll up to 2,500 patients at about 150 centers in nine countries. An independent data monitoring committee will review safety results as the trial progresses and the primary endpoint is the reduction in 28-day all-cause mortality.

¿This [enrollment] should take us about three years, if we need to enroll the entire complement of patients,¿ said John Pribble, associate director of clinical research at ICOS. ¿We are performing interim analysis during the study and there is the possibility to stop early because of efficacy.¿

Pafase is being jointly developed by ICOS and Japan-based Suntory Ltd.

Pribble said the independent committee will periodically review efficacy results and make a decision as to whether the trial should be stopped early or continue, basing the call on the 28-day mortality rate.

¿What we do is, we treat them and observe them for 28 days,¿ Pribble said. ¿We see what percentage of them survive the 28 days and compare them to placebo.¿ Pribble added that the patients in the trial will receive all treatments available, including Indianapolis-based Eli Lilly and Co.¿s product, Zovant, which has shown some success against sepsis, if it becomes commercially available.

Since the trial may be stopped early and predicting how many patients will be enrolled is difficult, pinning down a time for a new drug application filing for Pafase is not easy, but Pribble said it will be done with speed in mind.

¿The opinion is, we will know shortly after the last patient finishes the 28 days, but not only do we want to have the answers quickly, but we want to have validity in the results,¿ he said. ¿We will be very aggressive and file as quickly as possible.¿

Pafase is a recombinant human serum protein that inactivates platelet-activating factor, a pro-inflammatory mediator that has been found in excess amounts in the blood and lungs of patients with severe sepsis and severe trauma. The Phase II trial showed a statistically significant reduction in death from all causes compared to placebo ¿ a 14 percent death rate with Pafase and a 28.4 percent rate with placebo. (See BioWorld Today, April 24, 2000.)

¿We have very compelling and robust Phase II results,¿ said Pribble. ¿Based on those results, we are cautiously optimistic.¿

There is no shortage of failed sepsis drugs, littering the clinical pathway like empty beer cans on a country road. In the 90s, Synergen Inc., of Boulder, Colo.; Centocor Inc., of Malvern, Pa.; Immunex Corp., of Seattle; Cortech Inc., of Denver; Xoma Corp., of Berkeley, Calif.; and Celltech Group plc, of Slough, UK have seen drugs fail at the Phase II or Phase III stage. It¿s a past that is hard to miss when considering sepsis and it certainly hasn¿t slipped by ICOS.

¿We are well aware of the history of the indication,¿ Pribble said. ¿Rather than ignore it, we have done everything to work with it. Pafase has a unique method of action and we are working with a naturally occurring substance to do what the body does anyway.¿

ICOS¿ stock (NASDAQ:ICOS) moved up $2.87 Friday to close at $53.39.

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