Cell Therapeutics to Appeal FDA Decision on New Drug Application (NDA) for Pixantrone to Treat Relapsed/Refractory Aggressive Non-Hodgkin's Lymphoma
Pixantrone NDA transferred to newly created Division of Hematologic Products
SEATTLE, Sept 14, 2010 /PRNewswire via COMTEX/ --
Cell Therapeutics, Inc. ("CTI") (Nasdaq and MTA: CTIC) today announced that it intends to appeal the U.S. Food and Drug Administration's (the "FDA") previously disclosed decision regarding the pixantrone New Drug Application ("NDA") to treat patients with relapsed/refractory aggressive non-Hodgkin's lymphoma ("NHL"). CTI had requested accelerated approval of its NDA for this patient group for which there are no currently approved drugs. The FDA issued a Complete Response Letter to CTI related to this NDA stating, in part, that CTI should conduct an additional clinical trial prior to approval. CTI is preparing to file an appeal under the FDA's Formal Dispute Resolution process. CTI reached this decision by taking into account that CTI believes there are no approved or effective therapies for patients with relapsed or refractory aggressive NHL beyond second relapse, and that PIX 301 was the first and only randomized trial in this patient group to demonstrate significant improvement in clinically relevant endpoints including complete response rate, overall response rate, and progression free survival while being safe and effective in this indication.
"The PIX 301 study produced robust clinically meaningful results including improvement in response rate and progression free survival that could have a significant impact on treating the disease in this setting," said Dr. Stanley M. Marks, Director of Clinical Services and Chief Medical Officer for the University of Pittsburgh Cancer Centers and Chief of the Division of Hematology/Oncology at UPMC.
"After discussions with a number of leading U.S. and international lymphoma experts and leading biostatisticians, all of whom have reviewed the PIX 301 protocol, statistical plan and trial results, we felt encouraged to appeal the initial decision and have our data reviewed in the context of a trial that achieved statistically and clinically meaningful primary and secondary endpoints in this end stage patient population for whom there are no approved or effective agents," noted Jack Singer. M.D., Chief Medical Officer at CTI. "We are committed to conducting a confirmatory trial in this patient population but continue to strongly believe that the PIX 301 data met the requirements for accelerated approval with sufficient scientific rigor."
FDA regulations provide a Formal Dispute Resolution mechanism to obtain review of any FDA decision, including a decision not to approve an NDA, by raising the matter with the supervisor of the Office that made the decision. The Formal Dispute Resolution process exists to encourage open, prompt discussion of scientific (including medical) disputes and procedural (including administrative) disputes that arise during the drug development, new drug review, and post-marketing oversight processes.
CTI expects the FDA decision on the appeal in the fourth quarter of 2010.
CTI continues to prepare for the initiation of an additional pixantrone clinical study in the U.S. that would serve as either a post-approval confirmatory study or as a registration study for approval in the U.S. Also, CTI expects to file a Marketing Authorization Application ("MAA") for approval of pixantrone in Europe before the end of this year.
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.
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 http://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 CTI'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 European Medicines Agency,,that the FDA may not accept CTI's proposed design for the protocol of CTI's clinical trial and/or may request additional clinical trials, that if CTI conducts an additional clinical trial, it may not demonstrate the safety and effectiveness of pixantrone, that CTI cannot predict or guarantee the pace or geography of enrollment of its clinical trials, that CTI may not initiate a new clinical trial for pixantrone in 2010, that CTI submits a formal appeal, that the FDA may not accept CTI's formal appeal, that CTI cannot predict the outcome of the Formal Dispute Resolution process,that the FDA may not make its decision on the appeal in the fourth quarter of 2010, that CTI's appeal may not be successful, that CTI may not submit the MAA before the end of this year and 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, 10-Q and 8-K. 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.