ATLANTA, Dec. 9 /PRNewswire-FirstCall/ -- Pharmion Corporation today announced complete results from a Phase 3 multi-center, international, randomized study of Vidaza(R) (azacitidine for injection) in the treatment of patients with higher-risk myelodysplastic syndromes (MDS) demonstrating that Vidaza provides a significant survival benefit compared to conventional care regimens (CCR) in higher-risk MDS patients. The median overall survival advantage for Vidaza-treated patients compared to CCR-treated patients in this, the largest clinical trial in MDS, was 9.4 months (24.4 months vs. 15 months; log rank p=0.0001). The hazard ratio describing this treatment effect was 0.58 (95 percent confidence interval of 0.43 to 0.77). These data, along with results from 18 additional studies of Vidaza, are being presented at the 49th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Atlanta.
"As the only hypomethylating agent, and, in fact, the only drug to have shown an improvement in overall survival, we believe Vidaza now stands alone as the standard of care for higher risk MDS patients," said Patrick J. Mahaffy, president and chief executive officer of Pharmion. "In addition to the unprecedented improvement in overall survival, 45 percent of patients on Vidaza achieved transfusion independence compared to 11 percent on CCR, and for patients on Vidaza, the median time to transformation to AML during the treatment period was 26 months, compared to 12 months for patients on CCR therapy. These data provide further evidence of the substantial benefit that Vidaza provides to higher-risk MDS patients in prolonging their lives."
"The data from this trial further confirm that Vidaza should be considered first-line therapy for patients with higher-risk MDS," said Pierre Fenaux, M.D., principal investigator of the Phase 3 study, Professor of Hematology at the University of Paris, and Head, Department of Clinical Hematology, Hopital Avicenne, France. "The results from this trial are robust and clinically meaningful and represent an important advance in the treatment of higher-risk MDS patients."
Professor Fenaux will deliver an oral presentation titled "Azacitidine (AZA) Treatment Prolongs Overall Survival (OS) in Higher-Risk MDS Patients Compared with Conventional Care Regimens (CCR): Results of the AZA-001 Phase III Study" (Abstract 817) on Tuesday, December 11, 2007 at 7:30 a.m. Eastern time. Professor Fenaux presented data from this study this morning at a media briefing sponsored by ASH.
The primary objective of this multi-center, international, randomized, open-label, parallel-group, Phase 3 trial was to demonstrate superiority in overall survival of Vidaza versus CCR in higher-risk MDS patients. The study evaluated 358 higher-risk MDS patients at sites in the U.S., Europe, and Australia. At baseline, approximately 90 percent of patients were considered to have higher-risk MDS, based on subsequent independent review of FAB subtypes or IPSS classification. Patients were assigned to treatment with Vidaza (N=179; 75 mg/m2/day SC for seven consecutive days every 28 days) or CCR for the treatment of MDS. Patients assigned to CCR could receive either BSC alone (N=105), low-dose cytarabine (LDAC; N=49), or standard chemotherapy (StdChemo; N=25). Median number of cycles for Vidaza was nine; for the CCR arm, the median number of cycles was as follows: BSC seven cycles, LDAC 4.5 cycles and StdChemo one cycle.
With a median follow-up of 21.1 months, Vidaza demonstrated a statistically significant overall survival advantage over CCR (24.4 months vs. 15 months; stratified log rank p=0.0001). At two years, Vidaza demonstrated a two-fold advantage in overall survival over CCR (51 percent vs. 26 percent; log rank p<0.0001). Among patients with poor cytogenetic profiles (as defined by IPSS, 28 percent of enrolled patients), median survival was 17.2 months in the Vidaza arm, compared to six months in the CCR arm (log rank p=0.01).
Treatment with Vidaza was well tolerated, demonstrating a safety profile consistent with previous experience.
Vidaza is the first of a new class of anti-cancer compounds known as demethylating agents, a subset of a category of drugs referred to as epigenetic therapies. Epigenetics refers to changes in the regulation of gene expression. DNA methylation and histone deacetylation are two of the more widely studied epigenetic mechanisms.
Vidaza Data at ASH
Date / Time / Location: December 11, 2007; 7:30-9:00 a.m., Thomas B Murphy Ballroom 4, Georgia World Congress Center
Session: Myelodysplastic Syndromes: Advances in Therapeutic Options -- Oral Session 7:30 a.m.: Azacitidine (AZA) Treatment Prolongs Overall Survival (OS) in Higher-Risk MDS Patients Compared with Conventional Care Regimens (CCR): Results of the AZA-001 Phase III Study (Abstract #817). -- Oral Session 7:45 a.m.: Maintenance Treatment with Azacytidine for Patients with High Risk Myelodysplastic Syndromes or Acute Myeloid Leukemia in Complete Remission after Intensive Chemotherapy (Abstract #818). -- Oral Session 8:00 a.m.: Results of the Initial Treatment Phase of a Study of Three Alternative Dosing Schedules of Azacitidine (Vidaza) in Patients with Myelodysplastic Syndromes (MDS) (Abstract #819).
Date / Time / Location: December 8, 2007; Viewing 9:00 a.m.-7:30 p.m., Presentation 5:30-7:30 p.m., Hall B4 of Georgia World Congress Center
Session: Acute Myeloid Leukemias: Therapy, Excluding Transplantation I -- Poster Board No. 65-I: Report of a Phase I/II Study of 5-Azacitidine and Cytarabine in Patients with Relapsed, Refractory Acute Myelogenous Leukemia (Abstract #911).
Date / Time / Location: December 8, 2007; Viewing 9:00 a.m.-7:30 p.m., Presentation 5:30-7:30 p.m., Hall B4 of Georgia World Congress Center
Session: Myeloproliferative Syndromes: Biological -- Poster Board No. 699-I: Hypermethylation of CXCR4 Promoter, and Its Reactivation by Hypomethylating Agent, in CD34 + Cells from Primary Myelofibrosis Patients (Abstract #1545).
Date / Time / Location: December 8, 2007; Viewing 9:00 a.m.-7:30 p.m., Presentation 5:30-7:30 p.m., Hall B4 of Georgia World Congress Center
Session: Myelodysplastic Syndromes: Clinical Studies, Including Transplantation
-- Poster Board No. 603-I: Outcomes of MDS Patients with Chromosome 7 Abnormalities Treated with 5-Azacytidine (Abstract #1449). -- Poster Board No. 605-I: A Phase II Study of Intravenous Azacitidine Alone in Patients with Myelodysplastic Syndromes (Abstract #1451). -- Poster Board No. 606-I: Therapy of Myelodysplastic Syndrome (MDS) with Azacitidine Given in Combination with Etanercept: A Phase II Study (Abstract #1452). -- Poster Board No. 612-I: Preliminary Results from a Phase I Study of Revlimid (Lenalidomide) in Combination with Vidaza (Azacitidine) in Patients with Advanced Myelodysplastic Syndromes (MDS) (Abstract #1458).
Date / Time / Location: December 9, 2007; Viewing 9:00 a.m.-8:00 p.m., Presentation 6:00-8:00 p.m., Hall B4 of Georgia World Congress Center
Session: Acute Myeloid Leukemias: Therapy, Excluding Transplantation II -- Poster Board No. 25-II: 5-Azacytidine Augments the Cytotoxicity of Mylotarg toward AML Blasts In Vitro and In Vivo (Abstract # 1835). -- Poster Board No 39-II: Treatment of AML with Azacytidine (AZA): Current Results of the French ATU Program (Abstract #1849).
Date / Time / Location: December 9, 2007; Viewing 9:00 a.m.-8:00 p.m., Presentation 6:00-8:00 p.m., Hall B4 of Georgia World Congress Center
Session: Myelodysplastic Syndromes: Molecular Biology and Pathogenesis -- Poster Board No 638-II: PI-PLCbeta1 Expression in Patients with High- Risk Myelodysplastic Syndromes Is Affected by Azacitidine Treatment (Abstract #2448).
Date / Time / Location: December 9, 2007; Viewing 9:00 a.m.-8:00 p.m., Presentation 6:00-8:00 p.m., Hall B4 of Georgia World Congress Center
Session: Myelodysplastic Syndromes: Prognosis and Clinical Correlative Studies
-- Poster Board No. 656-II: FISH-Analyses of Circulating CD34+ Cells in MDS-Patients -- A Suitable Method to Measure and Predict Response to 5-Azacytidine (Abstract #2466).
Date / Time / Location: December 9, 2007; Viewing 9:00 a.m.-8:00 p.m., Presentation 6:00-8:00 p.m.., Hall B4 of Georgia World Congress Center
Session: Disordered Epigenetic Regulation in Hematologic Malignancy -- Poster Board No. 312-II: DNA Methylation Analysis of 807 Genes in Chronic Myeloid Leukemia and Acute Promyelocytic Leukemia (Abstract #2122). -- Poster Board No. 402-III: Up-Regulation of miR-195 Expression Leads to Decreased Expression of Basic Fibroblast Growth Factor in CLL Patients Treated with DNA Methylation Inhibitors (Abstract #3183).
Date / Time / Location: December 10, 2007; 1:30-3:00 p.m., Rooms B216- B217, Georgia World Congress Center
Session: Thalassemia: Pre-Clinical and Clinical Advances: -- Oral Session 1:45 p.m.: Neither DNA Hypomethylation or Changes in the Kinetics of Erythroid Differentiation Account for 5-Azacytidine's Ability To Induce Human Fetal Hemoglobin (Abstract 572).
Date / Time / Location: December 10, 2007; 1:30 -3:00 p.m., Rooms A411- A412, Georgia World Congress Center
Session: Acute Myeloid Leukemias: Therapy, Excluding Transplantation- Novel Therapies
-- Oral Session 2:45 p.m.: Phase I/II Study of MGCD0103, an Oral Isotype- Selective Histone Deacetylase (HDAC) in Combination with 5-Azacitidine in Higher-Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML) (Abstract #444).
Date / Time / Location: December 10, 2007; Viewing 10:30 a.m.-7:00 p.m., Presentation 5:00-7:00 p.m., Hall B4 of Georgia World Congress Center
Session: Clinical Care: Transplantation Regimen Toxicities and Engraftment II
-- Poster Board No. 231-III: A Dose and Schedule Finding Study of Maintenance Therapy with Low-Dose 5-Azacitidine (AZA) after Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for High-Risk AML or MDS (Abstract #3012). -- Poster Board No. 232-III: Efficacy of Azacytidine (5-AC) Given as Maintenance of Salvage Therapy for Patients with Acute Leukemia Post Allogeneic Stem Cell Transplantation (HSCT) (Abstract #3013). About Vidaza
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. 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).
Vidaza is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of Vidaza required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of Vidaza cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non- proliferating cells are relatively insensitive to Vidaza. Vidaza was approved for IV administration in January 2007.
About Epigenetics
Vidaza is the first of a new class of anti-cancer compounds known as epigenetic therapies. Epigenetics refers to changes in the regulation of gene expression, and DNA methylation and histone deacetylation are two of the more studied epigenetic regulators of gene expression. Epigenetic changes can silence gene expression and, unlike DNA mutations, may be reversed by targeting the mechanisms involved. The silencing of key cell cycle control genes and tumor suppressor genes through these two mechanisms of epigenetic regulation has been demonstrated in vitro and in vivo in hematological malignancies and in solid tumors. These key growth control genes can be re- expressed in cancer cells when DNA hypermethylation is reversed by Vidaza. 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.
About MDS
Myelodysplastic syndromes, or MDS, are a group of diseases in which the bone marrow does not function normally, resulting in the production of malformed or immature blood cells. MDS affects approximately 40,000-50,000 people in the United States and 75,000-85,000 patients in Europe. The majority of patients with higher-risk MDS eventually experience bone marrow failure. Up to 50 percent of MDS patients succumb to complications, such as infection or bleeding, before progressing to acute myeloid leukemia (AML). MDS patients have a median survival of four months to five years depending on risk stratification. Higher-risk patients have a median survival of five to 14 months. Alleviation of disease-related complications, including transfusion requirements and hematologic improvement are key treatment goals in lower-risk MDS. Altering the natural history of disease is one of the most important treatment goals in higher-risk MDS.
Important Safety Information
Vidaza is contraindicated in patients with a known hypersensitivity to Vidaza or mannitol and in patients with advanced malignant hepatic tumors.
In clinical studies, the most commonly occurring adverse reactions by SC route 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%). The most common adverse reactions by IV route also included petechiae (45.8%), rigors (35.4%), weakness (35.4%) and hypokalemia (31.3%).
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 Vidaza is potentially hepatotoxic in patients with severe pre- existing hepatic impairment, caution is needed in patients with liver disease. In addition, Vidaza 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 Pharmion
Pharmion is a leading global oncology company uniquely 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 http://www.pharmion.com/.
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, including summary statements relating to the interim or preliminary results of clinical trials involving Vidaza. Such statements are based on current expectations and involve a number of known and unknown risks and uncertainties that could cause the final results to differ significantly from the results summarized by such statements. Preliminary results may not be confirmed upon final analysis of the detailed results of a trial and additional information relating to the safety, efficacy or tolerability of Vidaza may be discovered upon further analysis of clinical trial data and upon review and analysis of additional clinical trial data from this or other clinical trials. Additional risks and uncertainties relating to Pharmion and its business can be found in the "Risk Factors" section of Pharmion's Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2007, its Annual Report on Form 10-K for the year ended December 31, 2006 and in Pharmion's other 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 also disclaims any duty to comment upon or correct information that may be contained in reports published by the investment community.
