Panel Discussant Focuses on Longer Duration of Remission among Patients Achieving a Complete Remission with Pixantrone than Complete Remissions Achieved with Standard Chemotherapy
ORLANDO, June 2 /PRNewswire-FirstCall/ -- Therapeutics, Inc. ("CTI") (Nasdaq and MTA: CTIC) announced today that at the poster and discussion session of the Lymphoma and Plasma Cell Disorders Section at the 2009 American Society of Clinical Oncology ("ASCO") Annual Meeting, new subgroup analysis data were reviewed from the phase III EXTEND (PIX 301) clinical trial of pixantrone (the "PIX 301 EXTEND trial") demonstrating the effectiveness of pixantrone as therapy in patients with aggressive non-Hodgkin's lymphoma ("NHL") for whom anthracycline and related drugs are typically not to be used due to a high risk of cardiac toxicity, including cardiac failure.
Twenty-five of the 70 patients in the PIX 301 EXTEND trial had received prior cumulative doxorubicin doses in excess of the standard 300 mg/m2 associated with six cycles of first line CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. The median prior exposure of these patients, most of whom had received an anthracycline as part of a salvage regimen, was 386 mg/m2 (with a range of 306 mg/m2 to 778 mg/m2). Following treatment with pixantrone, ten of these 25 patients (40%) achieved a confirmed complete remission ("CR"), unconfirmed remission ("CRu") or partial remission ("PR") (CR=2, CRu= 5, 28%; PR=3, 12%) The lifetime cumulative doxorubicin equivalent dose following pixantrone was 579 mg/m2 (with a range of 361 mg/m2 to 1003 mg/m2). No patient developed a severe reduction (>=20%) in left ventricular ejection fraction (LVEF) and only one patient developed congestive heart failure (CHF). The total cumulative doxorubicin equivalent exposure per treatment cycle for all 68 patients treated with pixantrone is noted in the table below:
Treatment Cycle No. of Patients Pixantrone Lifetime Treatment Cumulative Cumulative Dose Dose Median mg/m2 Median mg/m2 1 68 74 365.2 2 54 148 430.2 3 43 209 498.1 4 36 275 571.8 5 25 356 631.5 6 22 427 695.0
Lifetime doses of doxorubicin of over 550 mg/m2 are associated with a high incidence of CHF if the cumulative dose levels were solely with a standard anthracycline.
An additional new subgroup analysis was highlighted by the ASCO discussant, which demonstrated the clinical benefit associated with achieving a CR or CRu with pixantrone. On an intent-to-treat basis, patients achieving a CR/CRu on the pixantrone treatment arm (n=14) had a significant increase in the duration of remission compared with the four patients who achieved a CRu with standard chemotherapy (7 months vs. 3.5 months, p=0.03, HR=0.279; a hazard ratio of less than one indicates a decreased risk of disease progression and a p-value of less than 0.05 indicates statistical significance).
An analysis was also reported that evaluated the effect of prior rituximab therapy on response rates. In the 38 patients who received pixantrone following prior treatment with rituximab, 12 patients (32%) achieved a CR/CRu/PR of which six patients (16%) achieved a CR/CRu. In the comparator arm, the response rate was seven out of 39 patients (18%) with three CRu.
The discussant noted that overall response rates of 30% in this population of patients would represent a significant advance in the treatment of aggressive NHL and commented that that while numerically higher, the overall incidence of cardiac events were lower than expected in this patient group with substantial prior doxorubicin exposure reflected by no significant change in ejection fraction from baseline to end of treatment.
"This data demonstrates that pixantrone can induce durable complete remissions not only in patients previously treated with standard front-line doxorubicin, but even in patients who received an anthracycline as part of a salvage regimen. Resistance to rituximab was not associated with resistance to pixantrone. In patients with high cumulative prior doxorubicin exposure, the frequency of severe cardiac toxicity following up to six cycles of additional pixantrone was lower than would be expected based on historical comparisons to studies of doxorubicin," said James A. Bianco, M.D., Chief Executive Officer of CTI. "We are pleased with these results as they underscore the potential for pixantrone in this difficult to treat patient population for whom few options exist."
About the PIX301 EXTEND Trial
The PIX 301 EXTEND clinical trial was a phase III single-agent trial of pixantrone for patients with relapsed or refractory, aggressive NHL who received two or more prior therapies and who were sensitive to treatment with anthracyclines. The trial enrolled 140 patients and patients were randomized to receive either pixantrone or another single-agent drug currently used for the treatment of this patient population and selected by the physician.
CTI previously announced that its pivotal phase III EXTEND (PIX 301) trial of pixantrone had achieved its primary endpoint with patients randomized to treatment with pixantrone achieving a significantly higher rate of confirmed (CR) and unconfirmed complete remissions (CRu) compared to patients treated with standard chemotherapy (14 out of 70 patients (20.0%) for the pixantrone arm compared to four out of 70 patients (5.7%) for the standard chemotherapy arm, p=0.02) with no patients in the standard chemotherapy arm achieving a confirmed complete remission.
The most common grade 3, 4 adverse event observed on the pixantrone arm was neutropenia in 41.2% of patients versus 19.4% on the comparator arm. However, the incidence of grade 3, 4 febrile neutropenia was only 7.4% versus 3.0% in the comparator arm. Grade 3, 4 infections had a similar incidence in both study arms (18% vs. 13%). Although the grade 3, 4 cardiac disorder was similar among the two treatment groups (1.5% vs. 1.5%), there was a slightly higher incidence of serious cardiac disorders in patients treated with pixantrone than among patients who received comparator agents (8.8% vs. 4.5%). Events considered cardiac disorders included cardiac arrest, congestive heart failure, myocardial infarction, cyanosis, pericardial effusion, and tachycardia.
The ASCO poster is available at http://www.celltherapeutics.com/investor_updates.
In April 2009, CTI began a rolling submission of a New Drug Application (the "NDA") with the U.S. Food and Drug Administration (the "FDA") for pixantrone to treat relapsed or refractory aggressive NHL. CTI expects to complete the submission this month and will request priority review, which if granted could lead to an approval decision from the FDA in the fourth quarter of 2009.
Pixantrone is also now available in Europe on a named patient basis.
Pixantrone (BBR 2778), is a novel major groove binder with an aza-anthracenedione molecular structure that differentiates it from the anthracyclines and other related chemotherapy agents. Anthracyclines are the cornerstone therapeutic for the treatment of lymphoma, leukemia, and breast cancer. Although they are sufficiently effective to be used as first-line (initial) treatment, they cause cumulative heart damage that may result in congestive heart failure many years later. As a result, there is a lifetime limit of anthracycline doses and most patients who previously have been treated with an anthracycline are not able to receive further anthracycline treatment if their disease returns. It also can be administered through a peripheral vein rather than a central implanted catheter as required for other drugs in this class.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit www.CellTherapeutics.com.
This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of pixantrone include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general, and with pixantrone in particular, including, without limitation, the potential failure of pixantrone to prove safe and effective (or increase remission rates or progress free survival) for treatment of relapsed or refractory aggressive NHL as determined by the FDA, the possibility that the NDA submission will not be completed in the second quarter of 2009, that priority review will not be granted by the FDA and that a decision by the FDA is not rendered in late 2009, CTI's ability to continue to raise capital as needed to fund its operations, competitive factors, technological developments, costs of developing, producing and selling pixantrone, and the risk factors listed or described from time to time in CTI's filings with the Securities and Exchange Commission including, without limitation, CTI's most recent filings on Forms 10-K, 8-K, and 10-Q. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise
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