The US Food and Drug Administration's (FDA) Oncologic Drugs Advisory Committee (ODAC) will review Cell Therapeutics, Inc.'s (CTI) resubmitted New Drug Application (NDA) for pixantrone on February 9, 2012 for the treatment of relapsed or refractory aggressive Non-Hodgkin's Lymphoma (NHL) in patients who failed two or more lines of prior therapy.
ODAC is a panel of experts that evaluates data concerning the efficacy and safety of marketed and investigational products for use in the treatment of cancer and makes recommendations to the FDA. The FDA will consider the recommendation of the panel, but the final decision regarding the approval of the product is made by the FDA.
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 are pleased the Office of Oncology Drug Products (OODP) chose to bring our pixantrone NDA back to ODAC for review now that we have provided additional information and data recommended by the Office of New Drugs (OND) that we believe addresses the issues raised in the OODP Complete Response Letter of April 2010,” stated James A Bianco, CEO of CTI. “We believe the NDA demonstrates that pixantrone has a favourable benefit risk profile compared to standard chemotherapy in patients with relapsed or refractory aggressive NHL, a patient population for which there are no approved agents.”
CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.