West Coast Editor

Despite less-than-spectacular Phase III data with Xyotax, its drug for advanced non-small-cell lung cancer, Cell Therapeutics Inc. intends to submit a new drug application seeking clearance to market the compound as a first-line monotherapy for women with poor performance status.

Xyotax links paclitaxel, the active ingredient in Taxol - a chemotherapeutic agent introduced in 1993 by Bristol-Myers Squibb Co., of New York - to a biodegradable polyglutamate polymer.

"We believe, based on the properties of the molecule, that it's preferentially trapped in tumor blood vessels," said Leah Grant, director of investor relations for Seattle-based CTI. Blood vessels in tumor tissue, unlike those in normal tissue, are porous to molecules like polyglutamate.

The drug missed its primary endpoint in three Phase III trials in NSCLC patients, showing only equivalent survival overall, instead of the hoped-for average 30 percent improvement. Trials compared Xyotax with paclitaxel/carboplatin, docetaxel or gemcitabine/vinorelbine. After the first blowup, CTI's stock fell by more than 47 percent. (See BioWorld Today, March 8, 2005, and May 3, 2005.)

But the company found good results in the female subset, and is pursuing that route in the U.S., though a similar filing for Xyotax in Europe is not expected to limit use of the compound to that gender.

"We're looking at a potential non-inferiority application there," Grant told BioWorld Today, and CTI is waiting for word from regulatory officials overseas on their statistical interpretation of non-inferiority.

CTI's stock (NASDAQ:CTIC) closed Wednesday at $2.59, up 1 cent.

Survival data from women tested in the Stellar 3 and Stellar 4 trials seem strong enough to try for approval, though the company acknowledged that missing the primary endpoints will make for a "challenging" review. Another study to confirm the findings in women is planned for the fourth quarter of this year.

Poor performance status is determined by using daily-living measures from a scale established by the Eastern Cooperative Oncology Group, or ECOG scoring, Grant said.

"We would hesitate to project timelines" for finishing that trial, she said.

In June, on the heels of disappointing Xyotax data, CTI sold Trisenox (arsenic trioxide), its one marketed product, to Frazer, Pa.-based Cephalon Inc. for up to $170 million, including $70 million in cash up front and a potential $100 million in milestone payments - cash the company said it would use for the Xyotax NDA and to advance another pipeline product, pixantrone, through Phase III trials in non-Hodgkin's lymphoma. (See BioWorld Today, June 14, 2005.)

Trisenox is approved in the U.S. and Europe as a second-line treatment for relapsed or refractory acute promyelocytic leukemia. Studies have been completed with the compound as a first-line treatment. Cephalon intends to conduct additional studies in order to expand the label.

Meanwhile, CTI is focusing on Xyotax, using results from two of three failed Phase III studies. "The data in women in those two trials were from the same [first-line] patient population," Grant said, referring to Stellar 3 and Stellar 4, whereas the Stellar 2 trial enrolled second-line patients.

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