ATLANTA, Dec. 11 /PRNewswire-FirstCall/ -- Pharmion Corporation today announced interim data from a Phase 2 clinical trial evaluating three alternative five-day dosing schedules for Vidaza(R) (azacitidine for injection) that demonstrated safety and response profiles which are consistent with those achieved with the FDA-approved seven-day regimen, as reflected in rates of hematologic improvement (HI) and red blood cell (RBC) transfusion independence. These responses were observed in a broad range of MDS patients, including FAB low-risk patients. These data were presented at the 49th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Atlanta.
“The data from this study suggest that a five-day schedule is as effective as the currently approved seven-day schedule at achieving RBC transfusion independence and hematologic improvement in MDS patients,” said Dr. Andrew R. Allen, executive vice president and chief medical officer of Pharmion. “A dosing schedule that circumvents the need for weekend dosing would provide a meaningful benefit in terms of convenience to these patients and clinicians.”
Roger M. Lyons, MD, FACP, principal investigator of the study at Cancer Care Centers of South Texas and U.S. Oncology Research San Antonio delivered an oral presentation titled “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).
In this Phase 2 prospective, multi-center, randomized, open-label 3-arm trial, a total of 151 MDS patients were randomized to one of three regimens administered subcutaneous every four weeks for six cycles: Vidaza 5-2-2 (75 mg/m2/day x 5 days, two days off therapy, two additional days at same dose as the first five days; N=50); Vidaza 5-2-5 (50 mg/m2/day x 5 days, followed by 2 days off therapy and five additional days at the same dose as the first five days; N=51); Vidaza 5 (75 mg/m2/day x 5 days; N=50). The majority of patients (57 percent) were classified with FAB low-risk disease (RA/RARS), while 33 percent had FAB higher-risk MDS (RAEB/RAEB-T).
“These trial data suggest that transfusion dependency is reduced with five-day dosing schedules,” said Dr. Lyons. “This could succeed in normalizing cytopenias and improve the daily lives of these patients.”
The study, which is ongoing, includes this preliminary analysis of the first six cycles of therapy. Across the three alternative dose regimens, between 44 and 55 percent of evaluable patients experienced HI, defined as major or minor in at least one cell line (erythroid, platelet, or neutrophil). This reflects HI of 44, 52, and 55 percent in the Vidaza 5-2-2, Vidaza 5-2-5, and Vidaza 5 arms, respectively.
Further, across the three alternative dose regimens, between 55 and 63 percent of patients who were red blood cell (RBC) transfusion dependent at baseline achieved transfusion independence. This reflects overall RBC transfusion independence rates of 55, 60, and 63 percent in the Vidaza 5-2-2, Vidaza 5-2-5, and Vidaza 5 arms, respectively. Among transfusion-dependent patients with FAB low-risk disease, RBC transfusion independence was achieved by 60, 56, and 61 percent, respectively.
Each dosing schedule offered a safety profile similar to the well- established profile seen with standard Vidaza dosing. No treatment-related mortalities were reported. Most treatment-related grade 3 and 4 adverse events were hematological.
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 (CMML).
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
Azacitidine is the first of a new class of anti-cancer compounds called epigenetic therapies. 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 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 and/or inappropriate histone deacetylation is inhibited by MGCD0103. 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 Myelodysplastic Syndromes (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 and typically do not achieve positive outcomes when treated with current conventional care regimens (CCR) including basic supportive care, chemotherapy, and Ara-C. 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 and the presentations referred to in this release contain forward-looking statements, including summary statements relating to 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. Top line or preliminary results may not be confirmed upon full 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 data from 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.
The scientific information discussed in this press release is preliminary and investigative. Vidaza has not yet been approved by the EMEA in the EU and the results described in this press release have not been approved for inclusion in the prescribing information for Vidaza by the FDA in the U.S. or any other regulatory authority.
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