The US Food and Drug Administration's (FDA) Division of Oncology Products 1 (DOP1) has notified that Cell Therapeutics, Inc.'s (CTI) October 2011 resubmitted New Drug Application (NDA) is considered a complete, Class 2 response to the FDA's April 2010 complete response letter (CRL).

A press release from CTI says that the US FDA has set a Prescription Drug User Fee Act (PDUFA) goal date of April 24, 2012 for a decision on the NDA. The NDA seeks accelerated approval of pixantrone to treat relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL) in patients who failed two or more lines of prior therapy.

Pixantrone is also under review for marketing approval in Europe with a Committee for Human Medicinal Products (CHMP) opinion on the application tentatively scheduled on January 19, 2012.

Pixantrone is a novel aza-anthracenedione that has distinct structural and physio-chemical properties that make its anti-tumour 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 in an effort 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 diffuse large lymphoma without unacceptable rates of cardiotoxicity.

"We look forward to working with the FDA and the European Medicines Agency ("EMA") to bring this drug to patients for whom there are currently no approved therapies," James A. Bianco, M.D. chief executive officer stated.

CTI appealed the CRL for the pixantrone NDA based on the results of the PIX301 clinical trial. The FDA's Office of New Drugs (OND) responded to CTI's appeal by providing CTI with an opportunity to resubmit the NDA with additional information, but without conducting an additional clinical trial. In June 2011, CTI met with the DOP1 to review CTI's plans for responding to the items noted in the CRL including CTI's plans for addressing the items noted by the OND in response to the appeal.