Cell Therapeutics, Inc. (CTI) has received notice that the European Medicines Agency (EMEA) has validated the expanded Paediatric Investigation Plan (PIP) that CTI filed in July for pixantrone for the treatment of relapsed or refractory, aggressive non-Hodgkin's lymphoma (NHL).
Following the validation, the EMEA Paediatric Committee (the PDCO) will review and comment or approve the content of paediatric plan. Once the PIP is approved, CTI will submit the Marketing Authorization Application (MAA) for pixantrone in the EU later this year. The paediatric programme will study pixantrone in paediatric patients aged 6 months to 18 years with the goal of determining the comparative safety and effectiveness of pixantrone compared to doxorubicin in paediatric lymphoid cancers.
"We are very pleased that the EMEA has validated the expanded PIP for pixantrone, as there is a real need for a less toxic, more effective anthracycline-like treatment option not only in lymphoma, but also possibly in other tumors," said Jack Singer, chief medical officer of CTI. "We look forward to completing the MAA submission, and continuing to pursue our goal of providing pixantrone as a treatment option to the patients who need it most."
CTI submitted the updated, expanded PIP in July 2010 after the PDCO recommended CTI expand the original PIP of September 2009 to include pixantrone's potential, but unproven, clinical benefit to children in reducing long-term cardiotoxicity associated with current curative therapies. The recommendation from the PDCO came following discussions with CTI about the preclinical and clinical pixantrone data, including PIX301, and the desire to explore the potential benefits pixantrone may offer to children with haematologic cancer.
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 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.