Cell Therapeutics, Inc. (CTI) (Nasdaq: CTIC; MTA) reported today preliminary cardiac safety results from a North American randomized phase II trial which substituted pixantrone for doxorubicin in the standard CHOP-R regimen. Called PIX203, the randomized trial compared CPOP-R directly to CHOP-R in the 1st line treatment of high risk patients with diffuse large B cell non-Hodgkin's lymphoma (DLBCL, NHL). While CHOP-R is considered the standard of care in front line treatment of DLBCL, exposure to cumulative doses of doxorubicin, an anthracycline, is associated with increasing incidence of irreversible, severe, and symptomatic cardiac toxicity. This correlation of doxorubicin exposure and increasing incidence of heart damage limits the use of doxorubicin beyond first line therapy and among patients with pre-existing cardiac disorders. Pixantrone a novel aza-anthracenedione, unlike anthracycline drugs like doxorubicin, is a potent DNA alkylator which lacks the structural motifs of doxorubicin that are responsible for the formation of toxic drug metal complexes and oxygen free radical generation, the putative mechanisms for anthracycline-related cardiac toxicity.
Preliminary data from a safety analysis of PIX203 indicates that patients treated with the CPOP-R regimen experienced significantly less frequent major reductions.
"These preliminary data from a randomized clinical trial appear to corroborate the preclinical and ex-vivo data regarding the differences in cardiotoxicity potential between doxorubicin and pixantrone," noted Jack Singer, M.D., Chief Medical Officer of CTI. "These data are consistent with the relatively low incidence of cardiac toxicity reported in the PIX301 randomized trial. In PIX 301, unlike PIX 203, patients had received near-lifetime limits of anthracyclines before entering the study, placing them at risk for unacceptably high incidence of severe cardiac toxicity if treated with additional doxorubicin. These data support the potential for pixantrone to be studied as first-line treatment for 20% of newly-diagnosed patients with pre-existing cardiac disease who are poor candidates for potentially curative treatment with doxorubicin-based regimens," Dr. Singer added.
CTI intends to file a marketing authorization application in Europe for pixantrone in the second half of 2010 and these results will be used as supportive data.