Firm remains on track to file for European approval during this year and will establish a new U.S. trial.
Cell Therapeutics’ Pixuvri™ (pixantrone dimaleate) boosted overall survival for non-Hodgkin lymphoma (NHL) patients by 21% in comparison with treatment using comparator agents, according to newly released pivotal trial results. Data from the PIX301 study showed that patients with relapsed or refractory aggressive NHL who demonstrated a complete or unconfirmed complete response to Pixuvri had a 63% probability of being alive after two years, compared with just a 20% probability of two-year survival for patients treated using the comparator agents.
Importantly, the study investigators point out, 76% of patients who achieved a complete response or unconfirmed complete response with Pixuvri had failed to respond to or had less of a response to their last multiagent therapy. Moreover, Cell Therapeutics adds, the 21% improvement in overall survival was independent of other known influential factors, such as prior rituximab use or stem cell transplantation, international prognostic index score, or refractory status based on univariate Cox regression analyses of survival.
The latest Phase III data comes within a month of Cell Therapeutics reporting positive preliminary results from a comparative Phase II trial in which pixantrone was substituted for doxorubicin in standard CHOP-R therapy for diffuse large B cell non-Hodgkin lymphoma. Preliminary safety data from study PIX203 showed that in comparison with the standard doxorubicin regimen, patients treated using the pixantrone regimen had over 20% less frequent major reduction in cardiac function as determined by serial measurements of left ventricular ejection fraction (LVEF), symptomatic congestive heart failure, and decline in LVEF.
“These data are consistent with the relatively low incidence of cardiac toxicity reported in the PIX301 randomized trial,” states Jack Singer, M.D., chief medical officer. “In PIX301, unlike PIX203, 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 percent of newly diagnosed patients with pre-existing cardiac disease who are poor candidates for potentially curative treatment with doxorubicin-based regimens.”
The firm says it is on track to submit pixantrone to the European regulatory authorities by the end of 2010. In March Cell Therapeutics received a knock-back in terms of its U.S. commercialization plans for pixantrone, when FDA’s Oncologic Drugs Advisory Committee voted unanimously against approval of the drug based on a previously filed NDA. The panel said the data was not adequate to support approval of pixantrone for patients with relapsed or refractory aggressive NHL. Since then Cell Therapeutics has confirmed plans to work with FDA on the design of a follow-on pivotal trial that would fulfill U.S. requirements for regulatory submission.
Pixantrone is a novel aza-anthracenedione with a molecular structure similar to other topoisomerase II inhibitors such as the anthracycline doxorubicin. Cell Therapeutics claims that important structural and physiochemical properties of its drug, however, means pixantrone is less likely to induce acute cardiotoxicity than other anthracyclines.
Preclinical studies have also shown pixantrone demonstrates significantly enhanced antilymphoma activity in comparison with doxorubicin, the firm states. Pixantrone has been available in Europe on a named patient basis since May 2009. While plans are ongoing for the additional U.S. trial, Cell Therapeutics says it will also pursue an expanded access program for the drug in the U.S.