Cell Therapeutics, Inc.

Cell Therapeutics, Inc. announced that pixantrone was shown to reduce the severity of clinical manifestation in the animal model of the autoimmune disease myasthenia gravis (MG). MG is a chronic auto-immune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body due to autoantibodies acting against the Acethyl-choline Receptor. The preclinical study was published in The Journal of Immunology (180:2696-2703, 2008) by Fulvio Baggi, M.D. and Renato Mantegazza, M.D., of the "Carlo Besta" Neurological Institute Foundation in Milan. The study com-pared pixantrone with the related drug, mitoxantrone, an agent currently approved to treat severe multiple sclerosis, also an autoimmune disease that attacks the central nervous system. In the current study, pixantrone was found to be more effective than mitoxantrone at improving both the laboratory and the clinical manifestations of the MG equivalent in rats. The authors con-cluded that "pixantrone is a promising immunosuppressant agent suitable for clinical investigation in myasthenia gravis, although additional experiments are needed to confirm its safety profile in prolonged treatments." Current therapeutic treatment options for myasthenia gravis include corticosteroids and immunosuppressive drugs, both of which are effective in most patients. However, some patients do not respond to the standard treatments, and side effects may limit prolonged administration. Mitoxantrone has a broad immuno-suppressive effect, but has cumulative cardiotoxicity and prolonged treatment can result in a decrease in left ventricular ejection fraction (LVEF -- the amount of blood the heart pumps out with each beat) or, rarely, congestive heart failure. Pix-antrone's mechanism of action is similar to that of mitoxantrone -- both act as DNA intercalating agents and inhibit topoisomerase II, but preclinical data indicate that pixantrone is less toxic to the heart than mitoxantrone and prolonged administration may be possible. "These results are intriguing, and, like the earlier data in animal models of multiple sclerosis, suggest that pixantrone may be of clinical utility in patients with severe myasthenia gravis or multiple sclerosis. We have been approached by European cooperative groups interested in performing clinical trials in both of these diseases," said Pezzoni, Ph.D., Scientific Director of Cell Therapeutics Inc.'s European branch, and one of the investigators in the preclinical study on EAMG. About the Preclinical Study In an in vitro rodent model, pixan-trone demonstrated a dose-dependent inhibition of T cell re-sponses up to complete suppression of the proliferation in EAMG. EAMG was induced in subject animals using acetylcholine (T-cell) receptor, the autoantigen at the neu-romuscular junction. The animals were randomly assigned to four treatment groups -- 1) preventive pixantrone (PIX)group, starting four days after immunization, 2) thera-peutic PIX group, starting four weeks after immunization, 3) thera-peutic mitoxantrone (MTX) group, starting four weeks after immunization, and 4) vehicle-treated animals as control groups. Doses of both pixantrone and mitoxantrone were equal to one-fourth of LD10 for single i.v. injection in animals. Al-though both pixantrone and mitoxantrone improved clinical symptoms, reduced weight loss and in-creased muscle acetylcholine receptor content compared with vehicle-treated rats, pixantrone appeared to be more effective at equitoxic doses. About Pixantrone Pixantrone is an investigational agent under development for the potential treatment of various hematological malignancies. It was de-veloped to improve the activity and safety of the anthracycline family of anti-cancer agents. Anthracyclines have been shown to be very active clinically in a number of tumor types. However, they are usually associated with cumulative heart damage that prevents them from being used in a large proportion of patients. Pixantrone has been designed to reduce the potential for these severe cardiotoxicities, as well as to potentially increase activity and permit simplified administration compared to the currently marketed anthracyclines. About Cell Therapeutics, Inc. Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit

Pixantrone