Xyotax has failed to meet the primary endpoint in another two Phase III non-small-cell lung cancer trials, but Cell Therapeutics Inc. intends to file for approval based on the drug's superior safety profile.

While results from the Stellar 2 and 4 trials were somewhat disappointing, the Seattle-based company's stock (NASDAQ:CTIC) fell only 12 cents Monday to close at $3.67. Investors might have expected the news, after Stellar 3 results in March showed the product missed its primary endpoint and had only an equivalent survival efficacy to paclitaxel used with carboplatin. The company's stock fell 47.5 percent when that news was made public. (See BioWorld Today, March 8, 2005.)

The Stellar studies were designed to show that Xyotax could increase the overall survival of patients while reducing serious side effects associated with the treatment of first-line or second-line NSCLC. Both Stellar 2 and 4 demonstrated equivalent survival and significant reductions in serious side effects when compared to either docetaxel or gemcitabine/vinorelbine. They both, however, missed the primary endpoints of superior overall survival.

Since Xyotax has shown itself to be as effective as conventional therapy, but less toxic and better tolerated, Cell Therapeutics plans to continue its talks with the FDA regarding the filing of a new drug application. The company previously had said it would file in the third quarter, but that was bumped back a month or two following the Stellar 3 results in March. If approved, a launch could occur in 2006.

In Stellar 4, patients receiving Xyotax had a median survival of 7.3 months and two-year survival of 15 percent, compared with 6.6 months and 10 percent for patients receiving either gemcitabine or vinorelbine. The drug was being evaluated as a first-line treatment of poor performance status patients with NSCLC.

Despite the missed endpoint, Xyotax patients experienced a significant reduction in all cardiac toxicities, gastrointestinal side effects, nausea and vomiting, and severe hematologic toxicities including anemia, neutropenia and thrombocytopenia. Significantly more patients (p=0.003) completed six courses of therapy on the Xyotax arm compared with the control arm. Grade III and IV neuropathy, however, was observed more frequently on the Xyotax arm.

In Stellar 2, researchers evaluated Xyotax vs. docetaxel for the second-line treatment of NSCLC. Both arms had a 6.9-month median survival, but Xyotax-treated patients experienced significantly fewer hematologic side effects than patients on the docetaxel arm, including Grade III or IV infections, severe neutropenia and febrile neutropenia. They also had a reduction in hair loss, fatigue, asthenia, breathing problems, severe hypoxia, mucositis and ocular toxicity. Severe neuropathy was higher on the Xyotax arm, at a dose of 210 mg/m2.

Patients in both trials were administered a 10-minute infusion of Xyotax without steroids and other premedications. Preclinical studies have indicated that Xyotax is preferentially trapped in the tumor blood vessels allowing more dose of chemotherapy to localize there, instead of in regions of normal tissue.

In March, Cell Therapeutics initiated a Phase III trial of Xyotax in 1,550 ovarian cancer patients. The product, which is paclitaxel linked to a polyglutamate chain, is not partnered.