Cell Therapeutics, Inc. (CTI) said the European Medicines Agency (EMEA) has accepted for review CTI's marketing authorization application (MAA) for Xyotax (paclitaxel poliglumex, CT-2103) for first-line treatment of patients with non-small cell lung cancer (NSCLC) with ECOG (Eastern Cooperative Oncology Group) performance status 2 (PS2).

CTI submitted the MAA at the beginning of March. The validation of the MAA for Xyotax initiates the marketing approval review process, which generally takes 15 to 18 months. The application is based on advice from the Scientific Advice Working Party, or SAWP, at the EMEA. The EMEA agreed that switching the primary endpoint from superiority to non-inferiority is feasible if the retrospective justification provided in the marketing application is adequate. The discussions with the SAWP focused on using the STELLAR 4 study as primary evidence of non-inferiority and the STELLAR 3 study as supportive of the MAA.

In the STELLAR 4 trial, single-agent Xyotax resulted in comparable survival to gemcitabine or vinorelbine in first-line patients and, with the exception of neuropathy known to be associated with taxane therapy, demonstrated significant reduction in several clinically meaningful toxicities, such as severe neutropenia and infection, and in the requirement for transfusions and use of haematopoietic growth factor support. In addition to improved tolerability, Xyotax offered more convenient administration compared to currently used treatments and a reduction in overall utilization of medical resources compared to gemcitabine or vinorelbine.

"CTI looks forward to working with the EMEA as it begins the review process for Xyotax," said James A. Bianco, M.D., president and CEO, CTI. "This is an important step toward making Xyotax available for lung cancer patients in Europe."

Xyotax (paclitaxel poliglumex, CT-2103) is an investigational, biologically enhanced, chemotherapeutic that links paclitaxel, the active ingredient in Taxol, to a biodegradable polyglutamate polymer, which results in a new chemical entity. When bound to the polymer, the chemotherapy is rendered inactive, potentially sparing normal tissue's exposure to high levels of unbound, active chemotherapy and its associated toxicities. Blood vessels in tumour tissue, unlike blood vessels in normal tissue, are porous to molecules like polyglutamate. Based on preclinical studies, it appears that Xyotax is preferentially distributed to tumours due to their leaky blood vessels and trapped in the tumour bed allowing significantly more of the dose of chemotherapy to localize in the tumour than with standard paclitaxel. Once inside the tumour cell, enzymes metabolize the protein polymer, releasing the paclitaxel chemotherapy. Preclinical and clinical studies support that Xyotax metabolism by lung cancer cells may be influenced by estrogen, which could lead to enhanced release of paclitaxel and efficacy in women with lung cancer compared to standard therapies.

Completed in 2005, the STELLAR trials were among the largest randomized, phase III trials in either second-line NSCLC or first-line PS2 NSCLC patients. STELLAR 2 tested Xyotax versus docetaxel for the potential second-line treatment of NSCLC patients. STELLAR 3 tested carboplatin in combination with either Xyotax or paclitaxel for the potential first-line treatment of PS2 patients with NSCLC. STELLAR 4 tested Xyotax versus either gemcitabine or vinorelbine for the potential first-line treatment of PS2 patients with NSCLC. While the STELLAR trials missed their primary endpoint of superior overall survival, the trials showed significant reductions in most of the severe toxicities associated with standard chemotherapy agents.