Cell Therapeutics, Inc. (CTI) announced that it met with and received feedback from the rapporteur and co-rapporteur regarding its Marketing Authorisation Application (MAA) for Xyotax (paclitaxel poliglumex, CT-2103).
The feedback supports submission of the MAA in the first quarter of 2008, earlier than the first half of 2008 that CTI was targeting. The rapporteur and co-rapporteur, who are assigned by the EMEA, are responsible for providing scientific advice on the evaluation of medicinal products. CTI plans to submit an MAA in Europe, based on the Stellar 4 phase III clinical trial results, for Xyotax as a single agent for first-line treatment of non-small cell lung cancer (NSCLC) in patients with poor performance status (ECOG performance status 2, PS2).
"The meetings were very productive and we appreciate the advice the rapporteurs provided us on how best to report our data and supporting literature for the utility of the comparator drugs gemcitabine and vinorelbine," said Scott C. Stromatt, M.D., Executive Vice President, Clinical Development and Regulatory Affairs. "Based on their feedback and agreement on several critical components of the application, we believe we will be in a position to submit our MAA in the first quarter, months ahead of our previous target."
Lung cancer remains the biggest cancer killer in Europe. The incidence of lung cancer in Europe is more than 13 percent of all cancers, and in 2000 resulted in nearly 350,000 deaths.
PS2 patients represent a subgroup of patients who are ambulatory and capable of self-care, but are unable to carry out any work activities, although they are up and about more than 50 percent of waking hours. PS2 non-small cell lung cancer (NSCLC) patients account for approximately 25 percent of all patients with NSCLC who require chemotherapy. There are presently no drugs approved to treat PS2 patients with advanced NSCLC. Current treatments for this group of patients are poorly tolerated, with most tolerating a median of two doses of chemotherapy and experiencing disease progression on average within six weeks. Most physicians will utilize single-agent gemcitabine or vinorelbine to treat these frail patients. Current treatments also have limited effectiveness, with median survival ranging from only ten weeks for single-agent treatment to just over 17 weeks for combination therapies.
The Stellar 4 phase III clinical trial tested Xyotax versus either gemcitabine or vinorelbine for the potential first-line treatment of poor performance status (PS2) patients with NSCLC. While the Stellar 4 trial missed its primary endpoints of significant improvement in overall survival, it did demonstrate significant reductions in many of the clinically relevant toxicities associated with gemcitabine or vinorelbine. Based on the clinical benefit of lower severe toxicities, reduced use of hematopoietic growth factors and transfusions, enhanced convenience, and reduced medical resource utilization and associated costs, in 2006 CTI received a positive opinion from the Scientific Advice Working Party (SAWP) of the EMEA that a switch from the superiority endpoint to a non-inferiority endpoint is feasible if adequate justification is provided in the marketing application.
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.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.