BOULDER, Colo., Dec. 7 /PRNewswire-FirstCall/ -- Pharmion Corporation reported today that data from several studies of its epigenetic therapies, Vidaza and MGCD0103, will be presented at the American Society of Hematology 48th Annual Meeting and Exposition in Orlando (December 9 - 12, 2006).
In May 2004, Vidaza became the first drug approved by the FDA for the treatment of patients with Myelodysplastic Syndromes (MDS). The FDA approved Vidaza, the first in a new class of drugs called demethylation agents, for treatment of all five MDS subtypes, which include both low-risk and high-risk patients. These subtypes include: refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) if accompanied by neutropenia or thrombocytopenia or requiring transfusions; refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL).
In January 2006, Pharmion licensed from MethylGene Inc. the global rights (excluding certain Asian markets) to MGCD0103 and its pipeline of HDAC inhibitor compounds for oncology indications in development. MGCD0103 is a class I selective histone deacetylase inhibitor, which is currently the subject of several clinical studies, including a Phase 2 program initiated in the third quarter of 2006.
The following clinical data, both on Vidaza in combination with HDAC inhibitors, will be presented in oral sessions:
* Significant Clinical Activity of the Combination of Azacitidine, Valproic Acid and All-Trans Retinoic Acid (ATRA) in Leukemia: Results of a Phase I/II study Abstract ID: 160 Andres O. Soriano et al. Oral Presentation at 8:15am on Monday, Dec. 11; Viewing 7:30-9:00 am, Hall F-5 * Combined Methyltransferase/HDAC Inhibition with Azacitidine and MS-275 in Patients with MDS, CMMoL and Acute Myelogenous Leukemia (AML): Clinical Response, Histone Acetylation and DNA Damage Abstract ID: 517 Steven D. Gore et al. Oral Presentation at 1:30pm on Monday, Dec. 11; Viewing 1:30-3:00pm, Room 330
The following clinical data, which includes both Vidaza and MGCD0103 as monotherapy and in combination therapies, will be presented in poster sessions:
* Hematologic Improvement, Transfusion Independence, and Safety Assessed Using Three Alternative Dosing Schedules of Azacitidine in Patients with MDS Abstract ID: 2662 Roger M. Lyons, et al. Poster #: 840-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Azacitidine Induction of Human Gamma-Globin Gene Expression: Experimental Evaluation of Current Models Abstract ID: 1581 Rodwell Mabaera, et al. Poster #: 709-I Time: Saturday, Dec. 9; Viewing 9:00 am-7:30 pm, Presentation 5:30-7:30 pm. * Epigenetic Modification Can Regulate the Stem Cell State of Hematopoietic Cells Abstract ID: 1356 Il-Hoan Oh, et al. Poster #: 484-I Time: Saturday, Dec. 9; Viewing 9:00 am-7:30 pm, Presentation 5:30-7:30 pm. * Treatment of High Risk MDS and AML Post-MDS with Azacitidine: Preliminary Results of the French ATU Program Abstract ID: 2664 Claire Fabre, et al. Poster #: 842-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Expression of Proliferation Related Genes in MDS and Secondary AML Patients with Resistance to Low Dose Vidaza and Thalidomide Abstract ID: 2658 Naomi Galili, et al. Poster #: 836-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Phase I/II Study of the Oral Isotype-Selective HDAC Inhibitor MGCD0103 in Combination with Azacitidine in Patients with High-Risk MDS or AML Abstract ID: 1954 Guillermo Garcia-Manero, et al. Poster #: 132-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Azacitidine Induces Hematologic Responses in a High Proportion of Patients with AML Refractory to or Not Eligible for Intensive Chemotherapy Abstract ID: 1953 Haifa K. Al-Ali, et al. Poster #: 131-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Effect of Failure to Respond to Targeted Therapy on Response to Cytotoxic Therapy in Patients Age 60 with Newly-Diagnosed AML Abstract ID: 1965 Elihu H. Estey, et al. Poster #: 143-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Azacitidine Plus Gemtuzumab Ozogamicin (GO): A Novel Combination in the Treatment of AML and High-Risk MDS in the Elderly Abstract ID: 1981 Sucha Nand, et al. Poster #: 159-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * A Phase II Study of Azacitidine for Patients with Myelofibrosis Abstract ID: 2706 Alfonso Quintas-Cardama, et al. Poster #: 884-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * DNA Methylation Inhibitors Upregulate MiRNA Expression in Patients with Chronic Lymphocytic Leukemia Abstract ID: 2257 Margaret K. Yu, et al. Poster #: 435-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Semenogelin 1 Expression in Myeloma Cells: Interaction between DNA Methylation, MeCP2 Protein and Specific Cytokines Abstract ID: 2242 Yana Zhang, et al. Poster # 420-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Expansion of Polyclonal CD4+CD25high Foxp3+ Regulatory T-Cells in High Risk MDS Abstract ID: 2641 Shahram Y. Kordasti, et al. Poster # 819-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. * Pre-Transplant Azacitidine May Improve Outcome of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients with MDS Abstract ID: 3664 Teresa Field, et al. Poster #: 893-III Time: Monday, Dec. 11; Viewing 10:30 am-7:00 pm, Presentation 5:00-7:00 pm. * Maintenance Therapy with Azacitidine after Allogeneic Stem Cell Transplantation for AML and High-Risk MDS: A Dose and Schedule Finding Study Abstract ID: 3668 Andres O. Soriano, et al. Poster #: 897-III Time: Monday, Dec. 11; Viewing 10:30 am-7:00 pm, Presentation 5:00-7:00 pm. * Azacitidine Down-Regulates Both IL-6 Signaling and NFkB Activity in Human Myeloma Cells Abstract ID: 3441 Tiffany Khong, et al. Poster # 670-III Time: Monday, Dec. 11; Viewing 10:30 am-7:00 pm, Presentation 5:00-7:00 pm. * A Phase I Study of MGCD0103 Given as a Twice Weekly Oral Dose in Patients with Advanced Leukemias or MDS Abstract ID: 1971.5 Jeffrey E. Lancet, et al. Poster #: 149.5-II Time: Sunday, Dec. 10; Viewing 9:00 am-8:00 pm, Presentation 6:00-8:00 pm. About Epigenetics
DNA methylation and histone deacetylation are two of the more studied epigenetic regulators of gene expression. Epigenetics refers to changes in the regulation of gene expression. Epigenetic changes can silence gene expression and, unlike DNA mutations, may be reversed by targeting the enzymes involved. The silencing of key cell cycle control genes and tumor suppressor genes through these two mechanisms of epigenetic regulation have been demonstrated in vitro and in vivo in hematological malignancies and in solid tumors. Vidaza has been shown to reverse the effects of DNA hypermethylation with subsequent gene re-expression and likewise MGCD0103 has been shown, in vivo, to reverse the effects of inappropriate deacetylation resulting in gene expression reactivation. The epigenetic approach to cancer therapy is that rather than using molecules that kill both normal and tumor cells, the silenced genes are reactivated through targeted epigenetic therapy, re-establishing the cancer cell's natural mechanisms to control abnormal growth.
Important Safety Information
Vidaza is contraindicated in patients with a known hypersensitivity to azacitidine or mannitol and in patients with advanced malignant hepatic tumors.
In clinical studies, the most commonly occurring adverse reactions were nausea (70.5%), anemia (69.5%), thrombocytopenia (65.5%), vomiting (54.1%), pyrexia (51.8%), leukopenia (48.2%), diarrhea (36.4%), fatigue (35.9%), injection site erythema (35.0%), constipation (33.6%), neutropenia (32.3%) and ecchymosis (30.5%). Other adverse reactions included dizziness (18.6%), chest pain (16.4%), febrile neutropenia (16.4%), myalgia (15.9%), injection site reaction (13.6%), aggravated fatigue (12.7%) and malaise (10.9%).
Because treatment with Vidaza is associated with neutropenia and thrombocytopenia, complete blood counts should be performed as needed to monitor response and toxicity, but at a minimum, prior to each dosing cycle.
Because azacitidine is potentially hepatotoxic in patients with severe pre-existing hepatic impairment, caution is needed in patients with liver disease. In addition, azacitidine and its metabolites are substantially excreted by the kidneys and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function.
Vidaza may cause fetal harm. While receiving treatment with Vidaza, women of childbearing potential should avoid becoming pregnant, and men should avoid fathering a child. In addition, women treated with Vidaza should not nurse.
About MDS
The highest prevalence of MDS is in patients over 60 years of age. According to the American Cancer Society and the Aplastic Anemia and MDS International Foundation, there is an estimated 10,000-30,000 new cases of MDS in the United States each year. Survival ranges from six months to many years for the different subtypes of MDS.
About Pharmion:
Pharmion is a biotechnology company focused on acquiring, developing and commercializing innovative products for the treatment of hematology and oncology patients in the U.S., Europe and additional international markets. Pharmion has a number of products on the market including the world's first approved epigenetic drug, Vidaza(R), a DNA demethylating agent. For additional information about Pharmion, please visit the company's website at www.pharmion.com.
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause Pharmion's future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include the outcome of ongoing clinical trials, the status and timing or regulatory approvals; the impact of competition from other products under development by Pharmion's competitors; the regulatory environment and changes in the health policies and structure of various countries; uncertainties regarding market acceptance of products newly launched, currently being sold or in development; fluctuations in currency exchange rates, and other factors that are discussed in Pharmion's filings with the U.S. Securities and Exchange Commission. Forward-looking statements speak only as of the date on which they are made, and Pharmion undertakes no obligation to update publicly or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.
Pharmion CorporationCONTACT: Anna Sussman, Director, Investor Relations and CorporateCommunications, Pharmion Corporation, +1-720-564-9150
Web site: http://www.pharmion.com/
