The European Medicines Agency (EMEA) Pediatric Committee (PDCO) today released its findings requested that Cell Therapeutics, Inc submit an updated Pediatric Investigation Plan (PIP) for pixantrone following discussions about the preclinical and clinical pixantrone data, including PIX301, and the desire to explore the potential benefits pixantrone may offer to children with hematologic cancer.

Following the request Cell Therapeutics, cexpects to submit a revised PIP to the EMEA by the end of the second quarter of 2010. The PIP outlines how the Company proposes to study the drug in children in order to benefit child health.

Similar to anthracyclines
Pixantrone is a novel aza-anthracenedione that has distinct structural and physio-chemical properties that make its anti-tumor 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.

Commenting on the request, Jack Singer, M.D., Chief Medical Officer of Cell Therapeutics noted: “We were pleased and encouraged that the pediatric experts on the PDCO believe that there is an important need for a less toxic and effective anthracycline-like agent, not only in lymphoma and also potentially in other tumors, and that it is important that pixantrone be evaluated in a pediatric population given its potential to fulfill this need”

“The PDCO was very helpful in outlining the type of phase I and phase II studies they would like to see included in our Marketing Authorization Application (MAA) for pixantrone and that these studies could be deferred until after the potential MAA approval next year.”

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