Cell Therapeutics, Inc. (CTI) said it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA) for Xyotax (paclitaxel poliglumex, CT-2103) for first-line treatment of patients with non-small cell lung cancer (NSCLC) who have ECOG (Eastern Cooperative Oncology Group) performance status 2 (PS2).

The application is based on a positive opinion CTI received from the EMEA's Scientific Advice Working Party, which agreed to review the application based on the existing results of the phase III clinical trials of Xyotax, known as the Stellar trials.

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.

The application will be formally reviewed for validation by the end of March. Upon validation, the marketing approval review process begins, which generally takes 15 to 18 months, the company informed.

"This is an important milestone for CTI and demonstrates our commitment to bring Xyotax to this underserved group of patients. Currently, there are no approved treatments for first-line use in PS2 patients with non-small cell lung cancer. Every day counts when treating patients who may have an average life expectancy of only six months, so quality of life and less time in the doctor's office or hospital are important benefits for these patients," said James A. Bianco, president and CEO, CTI. "We appreciate the efforts of all the people who made this submission possible, especially the investigators and patients who participated in the clinical trials."

CTI also has an ongoing phase III clinical trial, in conjunction with the Gynaecologic Oncology Group (GOG), studying Xyotax as monthly maintenance treatment in ovarian cancer.

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 oestrogen, 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 randomised, 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.