Cell Therapeutics, Inc. (CTI)  announced that it has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Pixuvri (pixantrone dimaleate) as monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL). The application submission follows a positive opinion from the EMA's Pediatric Committee (the PDCO), where PDCO agreed to CTI's Pediatric Investigation Plan (PIP) for Pixuvri.

"This is an important milestone for CTI, and underscores our commitment to making pixantrone available to patients who currently have no approved or effective therapies for this life threatening disease," said James A. Bianco, M.D., CEO of CTI. "We appreciate the efforts of all the people who made the MAA submission possible, especially the investigators and patients who participated in our clinical trial."

"PIX301 was not only the first and only randomized trial in this patient population, it was also the largest study ever conducted for patients with multiply relapsed and refractory aggressive NHL. The positive results of this trial are among the most effective ever reported in this group of patients," noted Ruth Pettengell, M.D., of St. George's Hospital, University of London, the principal investigator on the study. "The robustness of the drug's effect in prolonging progression free survival irrespective of risk factors lends to the strength and credibility of the clinical benefit provided to patients in the trial. Currently there are no approved drugs available to patients today as such pixantrone will be a valuable new addition to offer these patients a new hope for controlling their disease."

Pixantrone was granted orphan drug status by the EMA for the treatment of diffuse large B-cell lymphoma (DLBCL). CTI expects that the EMA will make a determination regarding the acceptance of the Pixuvri MAA submission for review by mid-November.

Pixantrone is a novel aza-anthracenedione that has distinct structural and physio-chemical properties that make its anti-tumor activity unique in this class of agents. Similar to anthracyclines, pixantrone inhibits Topo-isomerase II but unlike anthracyclines--rather than intercalation with DNA--pixantrone alkylates DNA--forming stable DNA adducts, with particular specificity for CpG rich, hyper-methylated sites. These structural differences resulted in significantly enhanced anti-lymphoma activity compared to doxorubicin in preclinical models. In addition, the structural motifs on anthracycline-like agents that are responsible for the generation of oxygen free radicals and the formation of toxic drug-metal complexes have also been modified in pixantrone to prevent the binding of iron and perpetuation of superoxide production--both of which are the putative mechanism for anthracycline induced acute cardiotoxicity. These novel pharmacologic differences may allow re-introduction of anthracycline like potency in the treatment of relapsed/refractory aggressive lymphoma without unacceptable rates of cardiotoxicity.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.