Cell Therapeutics, Inc. (CTI) announced that it will meet with the US Food and Drugs Administration's (FDA) Office of Oncology Drug Products in early June to discuss the re-submission of CTI's New Drug Application (NDA) for pixantrone for accelerated approval to treat patients with relapsed or refractory aggressive Non-Hodgkin's lymphoma (NHL). This meeting follows CTI's receipt of the FDA's Office of New Drugs' (the OND) response to CTI's appeal as announced on May 3, 2011, which allows CTI the opportunity to resubmit the NDA to the FDA with additional information for consideration of accelerated approval of the NDA based on the PIX 301 trial.
In the FDA's response to CTI's appeal, the FDA requested that CTI submit two items--an additional review of radiographs by an independent panel and additional information regarding circumstances of stopping the clinical trial prior to achieving the planned accrual to assure reviewers that efficacy assessments were not involved in the decision to stop accrual early.
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.
CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.