Cell Therapeutics will focus its submission for FDA approval for Xyotax (paclitaxel poliglumex) as first line treatment for advanced non-small cell lung cancer in women only.

Xyotax failed to demonstrate a survival benefit in its STELLAR 3 and 4 studies. However, although both pivotal trials missed the primary endpoints, the drug did produce a benefit in women, according to the company.

"We believe that the survival data demonstrated among women in the STELLAR 3 and 4 trials are important enough to warrant review and consideration for approval," Cell Therapeutics said Aug. 24.

The company plans to initiate a clinical study in support of the narrower application. A study in performance status-2 women with advanced NSCLC is slated to begin in the fourth quarter of 2005.

"We are committed to conducting a study to try to confirm the survival seen in women who received Xyotax in STELLAR 3 and 4," the company said.

Xyotax failed to show a survival advantage in the 381-patient STELLAR 4 study over either gemcitabine (Lilly's Gemzar ) or vinorelbine (GlaxoSmithKline's Navelbine and generics) for first-line treatment of PS2 NSCLC.

In the 400-patient STELLAR 3 trial, Cell Therapeutics' proprietary paclitaxel formulation failed to demonstrate superiority over the conventional paclitaxel arm in the primary survival analysis. However, Xyotax did meet statistical significance for a pre-specified non-inferiority analysis.

After showing significant non-inferiority results in STELLAR 3, Cell Therapeutics had hoped to amend the primary endpoint for STELLAR 2 to non-inferiority (¹ Also see "STELLAR Failure Prompts Cell Therapeutics To Amend Next Xyotax Trial" - Pink Sheet, 7 March, 2005.).

However, FDA rejected Cell Therapeutics' efforts to pursue approval of its proprietary paclitaxel formulation based on non-inferiority data.

"Based on our discussions with FDA, accelerated review and non-inferiority are not possible routes to pursue in the United States," Cell Therapeutics stated.

"We believe that a standard review based on the gender-specific survival advantage observed in women in the STELLAR 3 and 4 trials is the most appropriate registration strategy in the U.S," the company said.

In Europe, however, the company plans to seek approval for Xyotax in PS2 men and women with NSCLC using non-inferiority trials.

"The filing in Europe will also seek use as monotherapy in first-line PS2 patients with NSCLC, but is not expected to be limited to women," Cell Therapeutics said.

"However, additional input on the statistical interpretation of non-inferiority will be needed from the scientific committee of the European Medicines Agency prior to submitting a marketing authorization application," the company noted.

Cell Therapeutics acknowledged that STELLAR 3 and 4, having missed their primary endpoints, "will make for a challenging review" with FDA and European regulators.

- Turna Ray

Cell Therapeutics Will Pursue Xyotax Approval For Women With NSCLC

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