Seattle based Cell Therapeutics, Inc. (CTI) has resubmitted the pixantrone New Drug Application (NDA) to the US Food and Drug Administration's (US FDA) Division of Oncology Drug Products (DODP) for accelerated approval to treat relapsed or refractory aggressive Non-Hodgkin's Lymphoma (NHL) in patients who failed two or more lines of prior therapy.
CTI had appealed the US FDA's Complete Response Letter for the pixantrone NDA based on the results of the PIX301 clinical trial. In May 2011, the US FDA's Office of New Drugs (OND) responded to CTI's appeal recommending that CTI conduct an additional review of radiographs utilizing a new independent panel of radiologists to confirm the response and progression events noted in the pixantrone NDA in order to determine that efficacy had been established. CTI recently announced that a second independent radiology assessment of response and progression endpoint data confirmed the statistical robustness of the PIX301 efficacy data contained in the NDA.
In June 2011, CTI met with the DODP to review its plans for responding to the items noted in the Complete Response Letter (CRL), as well as its plans for addressing the items noted by the OND in response to the appeal. The Company believes the information contained within the resubmitted NDA adequately addresses the recommendations from the OND and items noted in the CRL.
“We believe the resubmitted NDA not only addresses the items in the Complete Response Letter, but confirms the reliability of the initial efficacy results, which we believe demonstrates that pixantrone does provide a clinical benefit to this patient population for which there are no currently approved therapies,” said James A Bianco, MD, CEO of CTI.
The DODP previously confirmed that the review of the NDA would be completed within six months from the date of resubmission, which should provide CTI an US FDA action date by April 2012.
Pixantrone is also under review for approval in Europe. The Company expects to receive its day 180 responses from the European Medicines Agency (the EMA) in this quarter.
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.