BOULDER, Colo., June 4 /PRNewswire-FirstCall/ -- Pharmion Corporation reported today findings from seven studies investigating the use of Vidaza(R) (azacitidine for injectable suspension) in hematologic and solid tumor cancers. The results of these studies were presented at the 42nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Atlanta, GA (June 2-6, 2006).
The seven studies investigate a variety of uses for Vidaza -- including alternative dosing schedules, and combination use with approved and/or investigational therapies, such as thalidomide, carboplatin and the histone deacetylase (HDAC) inhibitor valproic acid (VPA). Two of these studies explore the feasibility of the emerging epigenetic approach to cancer therapy by combining Vidaza, a demethylating agent, with the HDAC inhibitor VPA and, in one study, all-trans retinoic acid (ATRA). Lastly, two of the abstracts presented further clarify the impact of Vidaza on transfusion independence among people with myelodysplastic syndromes (MDS).
Data Presented Saturday, June 3
Epigenetic Approach to Cancer Treatment
Data Assess Effects of Vidaza, All-Trans Retinoic Acid (ATRA) and Valproic Acid (VPA) Combination Therapy in Patients with MDS and Leukemia (Abstract 6563, Poster #BB7)
Data from an ongoing phase I/II study evaluating the safety and efficacy of the combination of Vidaza, valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients with MDS and acute myelogenous leukemia (AML) were presented on Saturday, June 3. Nineteen patients enrolled in the study to date received a fixed dose of Vidaza (75mg/m2/day SC x 7 days), as well as one of three doses of VPA: 50, 62.5 and 75 mg/kg/day orally x 7 days. An ATRA dose of 45 mg/m2 orally daily x 5 days was started on day three. Sixteen patients are evaluable to date. One patient had a complete response (CR), two had a complete marrow response (marrow blasts < 5 percent) and one a CRP (same criteria as of CR but without complete platelet recovery). The CR occurred at a VPA dose of 75 mg/kg, and the other three responses occurred at 62.5 and 75 mg/kg doses. Overall response rate was 30 percent among 13 patients who have completed one course of treatment.
"Based on growing evidence supporting the potential of epigenetic approaches to cancer treatment, Pharmion has made a strategic decision to aggressively explore this approach, particularly by combining compounds such as Vidaza and HDAC inhibitors that are believed to be synergistic," said Patrick J. Mahaffy, Pharmion's president and chief executive officer. "We are pleased that data being presented at this meeting reinforce the feasibility of this approach, particularly in MDS and difficult-to-treat cancers."
Transfusion Independence in Patients with MDS
Data Analysis Highlights Effect of Vidaza on Transfusion Independence in Patients with MDS (Abstract 6576, Poster #CC8)
A retrospective analysis of data from three studies of Vidaza in patients with MDS was presented on Saturday, June 3. A total of 268 patients with a range of MDS subtypes received Vidaza in the three Cancer and Leukemia Group B (CALGB) studies (clinical studies 8421, 8921 and 9221, in which the French-American-British (FAB) criteria were originally used). Each of these studies evaluated administration of Vidaza 75 mg/m2/day for seven days given every 28 days in addition to best supportive care. The retrospective analysis was designed to assess the proportion of transfusion-dependent patients who became RBC or platelet independent during the studies, as well as the duration of transfusion independence. Transfusion independence was defined as maintaining a transfusion-free period of > 56 days. In patients who received Vidaza intravenously, 20 percent and 25 percent achieved RBC and platelet transfusion independence, respectively. These numbers increased to 36 and 45 percent for RBC and platelet transfusion independence, respectively, among patients who received Vidaza subcutaneously (SC) in a phase II study; 45 and 53 percent for patients who received Vidaza SC in the phase III study; and 53 and 69 percent for patients randomized to supportive care who crossed over to receive Vidaza in the phase III study (in study 9221 cross-over occurred if patients experienced progressive disease after 56 days). Median duration of transfusion independence was durable across all three studies (RBC=4.7-8.4 months, platelets = 3.8-9.5 months).
Data Examine Transfusion Independence Associated with Three Alternative Vidaza Dosing Schedules (Abstract 6574, Poster #CC6)
A summary of interim data from an ongoing phase II study evaluating the effect of three alternative Vidaza dosing schedules on transfusion requirements in patients with MDS was presented on Saturday, June 3. The standard Vidaza dose and schedule is 75mg/m2/day SC x 7 days. A total of 96 patients have enrolled in the multi-center study to date and been randomized to receive one of three Vidaza dosing schedules: Vidaza 75 mg/m2/day SC x 5 days followed by 2 days of no treatment, followed by 2 days of Vidaza 75mg/m2/day SC; Vidaza 50mg/m2/day SC x 5 days, followed by 2 days of no treatment, followed by Vidaza 50 mg/m2/day x 5 days; or Vidaza 75mg/m2/day SC x 5 days. Of 70 patients who are evaluable to date across all three treatment groups, hematologic improvement occurred in 54 to 60 percent. Among the 33 patients who were RBC transfusion dependent at baseline, 25 (76 percent) have become independent.
"The need for regular blood transfusions can be a significant physical and emotional burden for people with MDS," said Lew Silverman, MD, Associate Professor of Medicine and Oncological Sciences, Director of MDS/Myeloproliferative Disease Program, Mt. Sinai School of Medicine and the principal investigator for study 9221. "Reducing this burden or the impact of therapy required to achieve transfusion independence can have positive clinical effects for patients."
Vidaza in Combination to Treat Hematologic and Solid Tumor Cancers
Data Highlight Therapeutic Effect of Low-Dose Vidaza with Thalidomide in Patients with MDS and AML (Abstract 6570, Poster #CC2)
Data from a pilot study designed to evaluate the safety and efficacy of combination therapy with Vidaza and thalidomide in patients with MDS and AML were presented on Saturday, June 3. Twenty-nine patients received Vidaza at a dose of 75mg/m2/day SC x 5 days on a 28-day cycle and thalidomide starting at 50 mg/day and increasing to 100 mg/day. Of the 25 patients evaluable for outcome, 10 received five or more cycles of Vidaza. Fifty-six percent of patients (14 of 25) exhibited hematologic improvement and twenty-four percent (six of 25) experienced stable disease. Twenty percent had disease progression. Six patients experienced CR and are still receiving therapy.
Data Examine Potential of Vidaza in Combination with Carboplatin for Patients with Platinum-Resistant Epithelial Ovarian Cancer (Abstract 5087, Poster #Q5)
Data from a pilot study exploring the potential of Vidaza to re-sensitize ovarian cancer patients to platinum-based therapy were presented Saturday, June 3. Patients enrolled in the study, all of whom have extensive prior therapies (up to 6 prior chemotherapy regimens) and platinum-resistant disease, receive 75 mg/m2/day SC x 5 days of Vidaza and IV infusion of carboplatin on day two of each treatment cycle. Carboplatin is dose-escalated from AUC 4 to AUC 5. Treatment repeats every 28 days until toxicity, progression or patient withdrawal. Six patients enrolled to date have received a total of 16 cycles of Vidaza/carboplatin treatment, and no grade 2 or higher toxicities have been observed. Three patients are currently evaluable for response. One (seven cycles of treatment) achieved CR by CA 125 criteria and stable disease by imaging criteria; one patient (four cycles of treatment) displayed stable disease; and the third patient (two cycles of treatment) showed mixed response by CT criteria.
Data Presented Sunday, June 4
Epigenetic Approach to Cancer Treatment
Data Explore Tolerance of Low-Dose Vidaza in Combination with VPA in Patients with Advanced Cancers (Abstract 3060, Poster #Y1)
Data from an ongoing phase I study of low-dose Vidaza in combination with the HDAC inhibitor valproic acid (VPA) in patients with advanced cancers were presented on Sunday, June 4. This study is designed to assess the tolerance of the Vidaza and HDAC regimen, in addition to the ability of this combination to induce re-expression of silenced genes. Vidaza was administered subcutaneously for 10 days on a 28-day cycle, with a starting dose of 20 mg/m2. VPA was administered orally on a daily basis in titrated doses to therapeutic levels (75-100 mcg/mL). Of 22 patients enrolled to date, one with rapidly progressive disease (renal cell carcinoma) experienced stable disease for six months and three patients experienced stable disease for four months.
Abstracts referenced:
Phase I/II study of the combination of 5-azacytidine (5-AC), all-trans retinoic acid (ATRA) and valproic Acid (VPA) in patients with myelodysplastic syndrome (MDS) and leukemia
Abstract ID: 6563 A Soriano; MD Anderson Cancer Center; USA Poster #BB7 Time: June 3, 2006; 8:00 a.m.-12:00 p.m.
Transfusion independence in patients with myelodysplastic syndromes treated with azacitidine
Abstract ID: 6576 L Silverman, MD; Mount Sinai Medical Center; USA Poster #CC8 Time: June 3, 2006; 8:00 a.m.-12:00 p.m.
Transfusion independence assessed using three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes
Abstract ID: 6574 S Anthony, MD; US Oncology; USA Poster #CC6 Time: June 3, 2006; 8:00 a.m.-12:00 p.m.
Low dose Vidaza and thalidomide is an effective combination for patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML)
Abstract ID: 6570 P Westervelt; University of Massachusetts Medical Center; USA Poster #CC2 Time: June 3, 2006; 8:00 a.m.-12:00 p.m.
A phase I study of a hypomethylating agent azacitidine in combination with carboplatin in patients with platinum resistant epithelial ovarian cancer
Abstract ID: 5087 S Fu, MD; MD Anderson Cancer Center; USA Poster #Q5 Time: June 3, 2006; 2:00-6:00 p.m.
Phase I study of low-dose hypomethylating agent Azacitidine (5-AC) combined with the histone deacetylase inhibitor Valproic Acid (VPA) in patients with advanced cancers
Abstract ID: 3060 F Braiteh, MD; MD Anderson Cancer Center; USA Poster #Y1 Time: June 4, 2006; 2:00-6:00 p.m. About Vidaza
Vidaza was the first drug approved for the treatment of all five subtypes of myelodysplastic syndromes (MDS), including refractory anemia (RA), 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 azacitidine 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 azacitidine 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.
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 are approximately 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 therapy, Vidaza(R), a DNA demethylating agent. For additional information about Pharmion, please visit the company's website at www.pharmion.com.
For more information or for complete prescribing information about Vidaza, please call 1.866.PHARMION.
Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This release contains forward-looking statements, including summary statements relating to the 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. The clinical trials described in this release are being conducted by independent investigators and Pharmion does not control and cannot predict the final results of those trials. Top line 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 Pharmion's products may be discovered upon further analysis of clinical trial data and upon review and analysis of additional clinical trial data. 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 March 31, 2006, its Annual Report on Form 10-K for the year ended December 31, 2005 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.
2006 (C) Pharmion Corporation. All rights reserved.
Pharmion CorporationCONTACT: Breanna Burkart or Anna Sussman, Directors, Investor Relationsand Corporate Communications of Pharmion Corporation, +1-720-564-9150
Web site: http://www.pharmion.com/
