The European Medicines Agency (EMEA) has granted an orphan drug designation for pixantrone (BBR 2778, pixantrone dimaleate), an experimental topoisomerase II inhibitor with an aza-anthracenedione molecular structure, used for the treatment of Diffuse Large B-Cell Lymphoma (DLBCL).Pixantrone is an analogue of mitoxantrone with a similar mechanism of action on the effector function of lymphomonocyte B and T cells in experimental allergic encephalomyelitis but with lower cardiotoxicity. Pixantrone inhibits antigen specific and mitogen induced lymphomononuclear cell proliferation, as well as IFN-gamma production.Diffuse Large B-Cell Lymphoma accounts for about 80% of aggressive non-Hodgkin’s lymphoma. Cell Therapeutics, Inc., a biopharmaceutical company headquartered in Seattle, WA (USA), who will market the new drug candidate, expects to file the Marketing Authorization Application (MAA) in Europe for approval of pixantrone in mid-2010 and would be granted 10 year market exclusivity if it is approved.Today 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 treatment, they are known to 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. Pixantrone differentiates from anthracyclines and other related chemotherapy agents in that it exhibits less cardiotoxicity.Ongoing Clinical TrialsClinical trials substituting pixantrone for doxorubicin in standard first-line treatment of patients with aggressive non-Hodgkin’s lymphoma, had a reduction in severe side effects when compared to patients treated with standard doxorubicin-based therapy. Despite pixantrone patients receiving more treatment cycles, a three-fold reduction in the incidence of severe heart damage was seen as well as clinically significant reductions in infections and thrombocytopenia, and a significant reduction in febrile neutropenia. These findings could have major implications for treating patients with breast cancer, lymphoma, and leukemia, where debilitating cardiac damage from doxorubicin might be prevented.In the U.S., the Food & Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) plans to review the New Drug Application (NDA) for pixantrone for the treatment of relapsed/refractory aggressive non-Hodgkin’s lymphoma (NHL) on February 10, 2010. Pixantrone is a fast track designated product in the U.S. and is in review for approval by the FDA, with a Prescription Drug User Fee Act (PDUFA) date of April 23, 2010.Orphan drug designationOrphan drug designation is available in Europe for medical treatments and drugs intended to treat life-threatening or chronically debilitating conditions. Orphan drug designation can confer numerous benefits to companies developing such treatments, including regulatory assistance, reduced regulatory fees associated with applying for marketing approval, and assistance with clinical trial design.”Orphan drug designation for pixantrone in Europe demonstrates that there is clear unmet medical need for patients with DLBCL,” stated Craig W. Philips, President of CTI. “We will continue to work with the EMEA to move our application forward in Europe expeditiously as we prepare for potential commercial launch of pixantrone in the United States.”For more information:– Cavalletti E, Crippa L, Mainardi P, Oggioni N, Cavagnoli R, Bellini O, Sala F. Pixantrone (BBR 2778) has reduced cardiotoxic potential in mice pretreated with doxorubicin: comparative studies against doxorubicin and mitoxantrone. Invest New Drugs. 2007 Jun;25(3):187-95.- Beggiolin G, Crippa L, Menta E, Manzotti C, Cavalletti E, et al. Bbr 2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity. Tumori. 2001 Nov-Dec;87(6):407-16.Clinical Trials:– Pixantrone (BBR 2778) in Patients With Refractory Acute Myelogenous Leukemia (AML);- BBR 2778 for Relapsed, Aggressive Non-Hodgkin’s Lymphoma (NHL);- Dose Ranging Trial for Pixantrone in the FND-R Variant Regimen in Indolent Non-Hodgkin’s Lymphoma;- Fludarabine and Rituximab With or Without Pixantrone in Treating Patients With Relapsed or Refractory Indolent Non-Hodgkin Lymphoma;- Pixantrone or Other Chemotherapy Drugs in Treating Patients With Relapsed Non-Hodgkin’s Lymphoma;- Pixantrone, Cytarabine, Methylprednisolone, and Cisplatin in Treating Patients With Aggressive Non-Hodgkin’s Lymphoma in First Relapse;- A Trial in Patients With Diffuse Large-B-cell Lymphoma Comparing Pixantrone Against Doxorubicin (RAPID);- Combination Chemotherapy in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin’s Lymphoma;
