New Pixantrone Data Presented at Meetings at American Society of Hematology Conference
- PIX301 End of Study Results confirm effectiveness and strength of evidence across all endpoints
- Pharmacokinetic Analysis of Pixantrone Phase I-II-III trials demonstrates significant correlation between dose, exposure and efficacy
- Pixantrone 203 front line trial of 'CPOP+rituximab' shows marked reduction in early and late severe cardiac dysfunction with comparable response rates compared to doxorubicin containing 'CHOP+rituximab'
SEATTLE, Dec. 6, 2010 /PRNewswire-FirstCall/ -- Cell Therapeutics, Inc. ("the Company") (Nasdaq and MTA: CTIC) today announced new pixantrone end of study ("EOS") follow up results from the Company's pivotal phase III PIX301 trial, which results form the basis for the Company's recent Marketing Authorization Application (the "MAA") currently under review by the European Medicines Agency ("EMA").
The end-of-study results showed continued improvement
in the trial's primary and secondary endpoints with increased
statistical confidence around the endpoint results. At EOS, CR/CRu
(Complete Response ("CR")/Complete Response unconfirmed) rate
increased to 24% in the pixantrone arm compared to 7% among
comparator recipients (p=0.009) while ORR (Overall Response Rate)
increased to 40% versus 14% for comparator recipients (p=0.001).
The median duration of CR/CRu was 9.6 months for the pixantrone
group compared to 4.0 months for the comparator group. Pixantrone
patients experienced a 40% reduction in the risk of death or
progression over the two year study observation and follow up
period compared to standard chemotherapy (p=0.005, HR=0.60) and a
21% reduction in the overall risk for dying (p= 0.25, HR =0.79).
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 serious infections
was comparable between arms. Deaths due to an adverse event were
identical between both arms; there were more LVEF reductions in
pixantrone arm, however only two were grade 3 and all were
asymptomatic. The results were presented by Principal Investigator,
Ruth Pettengell, M.D. of St.
George's Hospital, University of London, the lead investigator for the phase
III PIX301 EXTEND trial.
"The end of study results strengthen the confidence and stability across the primary and secondary measures of efficacy," noted Dr. Pettengell. "The magnitude of complete and durable responses and PFS demonstrated by pixantrone are currently not achievable using standard of care and we would welcome the opportunity to utilize this new drug for the benefit of our patients."
The poster from the conference is available at www.celltherapeutics.com/investor_updates.
To demonstrate that the dose and schedule utilized in the PIX301 trial and proposed for the follow on PIX306 study, is an appropriate dose and exposure for maximizing efficacy while minimizing side effects, the Company had an expert pharmacokinetic exposure safety and efficacy analysis conducted on data from all of its phase I, II and III trials including relapsed refractory patients with solid tumor malignancies. At an investor meeting at ASH those data were presented demonstrating that the dose of pixantrone used in PIX301 and proposed for PIX306 is an appropriate dose demonstrating a significant correlation between exposure to pixantrone and enhanced anti-tumor response (Progression-Free Survival ("PFS")) while minimizing the risk for side effects (neutropenia). The PIX306 trial is currently planned to be a randomized, single-blind study comparing pixantrone + rituximab to combination gemcitabine + rituximab in patients with relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma ("NHL") who are not candidates for myeloablative chemotherapy and stem cell transplant.
A summary status update on the PIX203 front line trial of CPOP-rituximab versus CHOP-rituximab in high risk and elderly DLBCL was also presented at an investigator meeting at ASH. Given that median PFS has not yet been reached for the CPOP-R arm and the median OS has not yet been reached for both treatment arms the Company only provided a brief update on patient demographics, while summarizing key efficacy and safety endpoints of the study. The Company anticipates submitting the PIX203 data for presentation at scientific meetings once the survival and PFS data are mature. The summary update presented at ASH meeting is available for viewing on the Company's website www.celltherapeutics.com.
About the PIX301 EXTEND trial: PIX301 is the largest and only randomized trial comparing single agent pixantrone to a list of physician's choice of standard chemotherapy to patients with relapsed or refractory aggressive NHL who have failed two or more lines of therapy. There are currently no approved or effective agents for these patients. The successful PIX301 study results formed the basis of the Company's recent MAA submission to the EMA which was validated and accepted for review on November 17th, 2010.
In addition on December 2, 2010 the Company filed a formal appeal with the U.S. Food and Drug Administration (the "FDA") under the FDA's dispute resolution proceedings. The basis for the appeal is based on the Company's belief that the FDA diverged from accepted statistical principles and practices when the FDA applied a more stringent statistical significance level in concluding that the PIX301 primary analysis required an adjustment for type 1 error as if an interim analysis had been conducted. This was not the case in the PIX301 trial where only a single final analysis was undertaken. The Company expects to have a response to the appeal in the first quarter of 2011.
About PIX203 trial design: The PIX203 trial is a first-line randomized phase II study of the CHOP-R versus CPOP-R in high risk and elderly patients with previously untreated DLBCL The study evaluates replacing doxorubicin in the standard CHOP-R combination regimen with pixantrone as part of the CPOP-R regimen. The objective of the study was to demonstrate non-inferior complete response rates to standard doxorubicin-based therapy while producing significantly less severe acute and chronic cardiac toxicities. The Company plans to submit the results of this study for presentation at scientific meetings once median survival is reached in both treatment arms, to date median PFS has not yet been reached in the CPOP-R arm.
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. The Company believes that these structural differences resulted in significantly enhanced anti-lymphoma activity compared to doxorubicin in preclinical models. In addition, the Company believes 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.
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.
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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 and the market price of the Company's securities. 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 for the treatment of relapsed or refractory aggressive NHL and/or other tumors as determined by the FDA and/or the EMA, that the FDA may not accept the Company's proposed design for the protocol of the Company's PIX306 clinical trial and/or may request additional clinical trials, that if the Company conducts an additional clinical trial, it may not demonstrate the safety and effectiveness of pixantrone, that the Company cannot predict or guarantee the pace or geography of enrollment of its clinical trials, that the Company cannot guarantee when it will initiate a new clinical trial for pixantrone, that the FDA may not approve the Company's special protocol assessment, that the Company cannot predict the outcome of its appeal to the FDA, that the Company's appeal may not be successful, that the EMA may not approve the Company's MAA after review, the Company'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 the Company's filings with the Securities and Exchange Commission including, without limitation, the Company's most recent filings on Forms 10-K, 10-Q and 8-K. Except as may be required by law, the Company does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.
Lindsey Jesch Logan
Medical Information Contact:
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Posted: December 2010