Dacogen(TM) (Decitabine) for Injection Data Presented at the American Society of Hematology (ASH) 48th Annual Meeting and Exposition.
"We are extremely pleased to have 16 abstracts describing the activity of Dacogen at the 2006 ASH Annual Meeting," said Mary Lynne Hedley, Ph.D., Executive Vice President and Chief Scientific Officer of MGI PHARMA. "We continue to believe that Dacogen may have activity in a variety of malignancies, and are currently evaluating it in a broad development program including clinical studies in patients with MDS, AML, CML, and solid tumors."
Phase 2 Data Demonstrate Activity of Dacogen in Older Patients with AML (Abstract 1984)
Because elderly patients with AML are often considered to be at high risk of mortality after receiving standard induction therapy, additional approaches to managing this patient population may offer improved outcomes. A multicenter phase 2 trial of Dacogen is being conducted in elderly patients diagnosed with de novo or secondary AML or AML transformed from MDS with poor or intermediate risk cytogenetics. The primary endpoint of the trial is complete morphologic response rate (CR). Secondary endpoints included overall, relapse free and event free survival, other measures of response, and safety. Patients in this study received Dacogen at a dose of 20 mg/m2 intravenously for one hour daily for five consecutive days, repeated every four weeks. Preliminary efficacy results from 28 evaluable patients indicate an overall response rate of 29% (n=8), including two CRs, two complete cytogenetic responses (CRc), and four patients with morphologic complete response and incomplete blood count recovery (CRi). The median time to first response was three treatment cycles. The most common adverse events in this study possibly related to Dacogen were myelosuppression, fatigue, nausea, asthenia, dyspnea, diarrhea, and pneumonia. In addition to this phase 2 study, MGI PHARMA is conducting a multicenter, phase 3 trial of Dacogen in elderly AML patients.
Survival Benefit with Dacogen vs. Intensive Chemotherapy in Patients with High Risk MDS (Abstract 2652)
Although intensive chemotherapy can result in responses in patients with high risk MDS, it is also associated with considerable morbidity and mortality risk. A retrospective matched case-control analysis was conducted to compare the outcomes for MDS patients treated with Dacogen to a historical control group who received intensive chemotherapy. The complete remission rate, as defined by AML criteria, was 43% among patients treated with Dacogen and 52% among those who received intensive chemotherapy. However, mortality rates among Dacogen-treated patients were significantly lower at six weeks, three months, and two years compared to those patients who received intensive chemotherapy. At six weeks, the mortality rate was 3% among Dacogen-treated patients compared to 12% for those who received intensive chemotherapy. Patients treated with Dacogen had a median survival of 22 months, compared to 11 months for those patients who received intensive chemotherapy. The estimated two year survival rates were 47% and 25% for patients treated with Dacogen and intensive chemotherapy, respectively. This survival benefit for Dacogen was observed in young patients as well as those older than age 60. An EORTC-sponsored phase 3 study evaluating survival in MDS patients treated with Dacogen plus supportive care compared to supportive care alone is currently ongoing in Europe to further evaluate outcomes in this population.
Decitabine Induces Responses in Patients with MDS after Failure of Azacitidine Therapy (Abstract 518)
A phase 2 study was conducted to evaluate Dacogen in patients with MDS who have failed three or more courses of azacitidine treatment or who experienced severe azacitidine-related toxicity. Dacogen was administered to 14 patients at a dose of 20 mg/m2 intravenously for one hour daily for five consecutive days, repeated every four weeks. Responses were evaluated after at least three courses, unless disease progression occurred. Courses were repeated regardless of myelosuppression as long as MDS persisted in the bone marrow and no severe life threatening complications occurred. Among the 14 patients, three (21%) experienced a CR, one (7%) had a complete bone marrow response, five (36%) experienced disease stabilization, four had disease progression, and one died. The median number of courses required to achieve a response was three, with a median survival of six months. Grade three and four toxicities included fatigue, abdominal distention, syncope and hypokalemia.
Efficacy of Dacogen in the Treatment of Patients with Chronic Myelomonocytic Leukemia (CMML) (Abstracts 2652 and 2655)
Two poster presentations focused on the efficacy of Dacogen in treating patients with CMML. In a phase 2 study, a total of 19 patients with CMML received infusions of Dacogen at a dose of 20 mg/m2 for one hour daily for five consecutive days or two alternative schedules of 100 mg/m2 per course, repeated every four weeks. Response was evaluated by the modified International Working Group (IWG) criteria. Of the 19 patients, 11 (58%) had a complete response and two (11%) experienced hematologic improvement. Among six patients who responded to Dacogen and had pretreatment chromosomal abnormalities, one had a complete cytogenetic response and two had partial cytogenetic responses (greater than 50% reduction of cytogenetic abnormalities). The median survival was 19 months. The most frequently observed adverse events included nausea, vomiting, bone aches, liver dysfunction, bleeding, fatigue, and diarrhea.
A retrospective review of 28 patients with CMML who received Dacogen in previously-conducted phase 2 and phase 3 studies was performed to evaluate the complete response, partial remission, and hematologic improvement rates. In two single arm phase 2 studies and in a randomized, multicenter phase 3 study, patients received Dacogen intravenously at a dose of 15 mg/m2 every eight hours for three consecutive days, repeated every six weeks. In this CMML population, the overall response rate (ORR) was 25%, including a 14% complete response rate and an 11% partial response rate. In addition, 11% of patients experienced hematologic improvement. Adverse events included myelosuppression, nausea or vomiting, pneumonia (one fungal), epistaxis, diarrhea, and thrombocytopenia.
Below is the list of all Dacogen abstracts presented at the 2006 ASH annual meeting:
Abstract Number: 518
Decitabine Induces Responses in Patients with Myelodysplastic Syndrome (MDS) after Failure of Azacitidine Therapy. Session Type: Oral Session
Abstract Number: 556
Decitabine Targets the Erythroid Progenitor/Precursor Subpopulations for the Y-Globin Gene Demethylation in Baboon. Session Type: Oral Session
Abstract Number: 1582
Exportin 4, a Potential Amplifier of TGF-B Signaling, Is Increased in Primary Baboon Bone Marrow Erythroblasts Following Decitabine Treatment
Abstract Number: 1584
Differences in the Pattern of Histone H3 (K4) and (K27) Methylation throughout the -Globin Gene Locus in Baboon Fetal Liver and Adult Bone Marrow Erythroblasts Pre- and Post-Decitabine Treatment
Abstract Number: 1590
Recapitulation of the Fetal Pattern of Expression of the I and V-Globin Genes in Cultured Baboon CD34+ Bone Marrow Cells
Abstract Number: 1984
Phase II Study of Low-Dose Decitabine for the Front-Line Treatment of Older Patients with Acute Myeloid Leukemia (AML)
Abstract Number: 1965
Effect of Failure To Respond to Targeted Therapy on Response to Cytotoxic Therapy in Pts Age 60 with Newly-Diagnosed AML
Abstract Number: 2223
Decitabine and Vitamin D3 Differentially Increase C-Jun, PU.1, and Sp1 Hematopoietic Transcription Factors To Induce Monocytic Differentiation
Abstract Number: 2322
Hypomethylation Induction and Molecular Response after Decitabine Therapy in Chronic Myelomonocytic Leukemia (CMML)
Abstract Number: 2652
Survival Benefit with Decitabine Compared to Historical Experience with Intensive Chemotherapy in Patients with Higher Risk Myelodysplastic Syndrome (MDS)
Abstract Number: 2655
Decitabine Induces High Response Rates in Patients with Chronic Myelomonocytic Leukemia (CMML)
Abstract Number: 2676
Efficacy of Decitabine in the Treatment of Patients with Chronic Myelomonocytic Leukemia (CMML)
Abstract Number: 4923
Phase II Study of Decitabine in Myelofibrosis with Myeloid Metaplasia
Abstract Number: 5257
Non-Intensive AML/MDS Treatment with Low-Dose Decitabine Prior to Reduced-Intensity Conditioning (RIC) and Allogeneic Blood Stem Cell Transplantation of Older Patients
Abstract Number: 4573
Hemoglobin F Induction Is Frequent during Low-Dose 5-aza-2-Deoxycytidine Treatment of Older AML/MDS Patients
Abstract Number: 4303
Hydroxyurea with Azacitidine or Decitabine in Combination Is Antagonistic on DNA Methylation Inhibition
About Dacogen[TM] (Decitabine) For Injection
Dacogen[TM] (decitabine) for Injection was approved by the U.S. Food and Drug Administration on May 2 and is indicated for treatment of patients with myelodysplastic syndromes (MDS) including previously treated and untreated, de novo and secondary MDS of all French-American-British (FAB) subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), and Intermediate-1, Intermediate-2 and High-Risk International Prognostic Scoring System (IPSS) groups. Dacogen may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while using Dacogen. Men should be advised not to father a child while receiving treatment with Dacogen and for 2 months afterwards. The most commonly occurring adverse reactions with Dacogen include neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%). Please visit www.mgipharma.com for full prescribing information.
MGI PHARMA is currently conducting a phase 3 pivotal trial to evaluate Dacogen in patients with acute myeloid leukemia, or AML. Additional phase 2 studies are also underway to evaluate alternative dosing regimens for Dacogen in patients with MDS and in patients with AML and chronic myelogenous leukemia, or CML. A phase 3 EORTC-sponsored study of Dacogen in patients with MDS is ongoing in Europe.
About MGI PHARMA, INC.
MGI PHARMA, INC. is an oncology and acute care focused biopharmaceutical company that acquires, develops and commercializes proprietary products that address the unmet needs of patients. MGI PHARMA markets Aloxi[R] (palonosetron hydrochloride) Injection, Dacogen[TM] (decitabine) for Injection, and Gliadel[R] Wafer (polifeprosan 20 with carmustine implant) in the United States. The Company directly markets its products in the U.S. and collaborates with partners to reach international markets. For more information about MGI PHARMA, please visit www.mgipharma.com.
This news release contains certain "forward-looking" statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These forward-looking statements are not guarantees of MGI PHARMA's future performance and involve a number of risks and uncertainties that may cause actual results to differ materially from the results discussed in these statements. Factors that might cause the Companies' results to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to the ability of MGI PHARMA to successfully introduce Dacogen for Injection into the marketplace; acceptance by physicians and patients of the product; and Dacogen for Injection competing successfully with other therapies for MDS; and other risks and uncertainties detailed from time to time in the Companies' filings with the Securities and Exchange Commission including its most recently filed Form 10-Q or 10-K. MGI PHARMA undertakes no duty to update any of these forward-looking statements to conform them to actual results.
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|Date:||Dec 11, 2006|
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