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New Data Demonstrate Clinical Activity of Vidaza(R) in Combination With HDAC Inhibitors in the Treatment of Higher-Risk MDS and AML

Posted on: Monday, 11 December 2006, 18:00 CST

ORLANDO, Fla., Dec. 11 /PRNewswire-FirstCall/ -- Pharmion Corporation announced new data presented today from three studies of Vidaza(R) (azacitidine for injectable suspension) in combination with several histone deacetylase (HDAC) inhibitors, including Pharmion's licensed HDAC inhibitor, MGCD0103. These studies were presented at the 48th Annual Meeting and Exposition of the American Society of Hematology (ASH) in Orlando, December 9-12, 2006).

"It is becoming ever clearer that multiple epigenetic pathways typically operate in parallel to silence tumor suppressor genes in cancer cells," said Dr. Andrew Allen, Pharmion's chief medical officer. "By combining epigenetic therapies, such as DNA demethylating agents and HDAC inhibitors, we hope to induce suppressor gene re-expression and favorably influence the clinical course of cancer. These latest data at ASH position Pharmion as a leader in this very exciting area of cancer research."

Significant Clinical Activity of the Combination of Vidaza, Valproic Acid and All-Trans Retinoic Acid (ATRA) in Leukemia (Abstract 160)

Andres Soriano, MD, of the University of Texas, MD Anderson Cancer Center in Houston, delivered an oral presentation describing the interim results of a Phase 1/2 study evaluating Vidaza, a demethylating agent, and valproic acid, an HDAC inhibitor, in combination with ATRA in the treatment of high-risk MDS and AML.

In this interim analysis, which included 53 evaluable patients, 22 patients, or 42 percent, were responders, including 12 complete responders (23 percent), three complete responders without platelet recovery (six percent) and seven patients who demonstrated bone marrow response (13 percent).

Seventeen of the responses occurred in 33 previously untreated elderly patients, or an overall response of 52 percent in that population, including 11 complete responders (33 percent), three complete responders without platelet recovery (nine percent) and three patients who demonstrated bone marrow response (nine percent).

The median number of courses to response in both the overall patient population and previously untreated patients was one.

This combination appears to be more active than single agent Vidaza in AML, and the study continues to accrue.

Phase 1 Study of Vidaza plus MS-275 in Patients with MDS, CMMoL and AML Shows 44 Percent Response Rate (Abstract 517)

Steven Gore, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, delivered an oral presentation describing the results of a Phase 1 study of Vidaza plus HDAC inhibitor MS-275 in patients with MDS, CMMoL and AML.

In this study, 12 of 27 evaluable patients, or 44 percent, responded, including two complete responders, four partial responders and six that demonstrated hematologic improvement in two or more cell lines. Combining AML with trilineage dysplasia and MDS patients, responses were seen in 10 of 20 patients.

The median time to first objective hematologic response was two cycles; median time to best hematologic response was four cycles.

The relative contribution of MS-275 is currently under examination in an ECOG study randomizing patients to the Vidaza/MS-275 combination versus the comparable dose schedule of Vidaza alone.

Vidaza in Combination with MGCD0103 in High-Risk MDS and AML Shows Response in Phase 1 Portion of Study and Appears Well-Tolerated (Abstract 1954, Poster 132-II)

Guillermo Garcia-Manero, MD, of the MD Anderson Cancer Center in Houston, delivered a poster presentation describing the results of a Phase 1/2 study of Vidaza in combination with MGCD0103 in patients with high-risk MDS and AML. MGCD0103 is the oral isotype-selective HDAC inhibitor that Pharmion is developing with its partner MethylGene, Inc., and this trial is the first clinical study to assess their use in combination.

This study utilizes Vidaza at the FDA-approved dose and an escalating dose of MGCD0103. At the time of this analysis, MGCD0103 was being dosed at 110 mg, 3 times per week. Its MTD is under evaluation.

Of the 23 patients enrolled, 30 percent had demonstrated a response at the time of analysis. Three patients have achieved a complete response, with time to response ranging from two to five cycles. Three complete responses without neutrophil recovery and one partial response have been observed, with responses occurring after one cycle of therapy.

The pharmacokinetics of both MGCD0103 and Vidaza appear to be unaltered by co-administration. This combination therapy demonstrated substantial reduction in HDAC activity.

"The data presented at ASH for Vidaza in combination with HDAC inhibitors further validates our belief that epigenetic therapies will be a major focus in hematology and oncology research in the future," said Patrick J. Mahaffy, Pharmion's president and chief executive officer. "We believe that the study of combination therapies, particularly with epigenetic drugs like Vidaza and MGCD0103, will continue to increase in importance."

About Epigenetics

DNA methylation and histone deacetylation are the two most studied epigenetic regulators of gene expression. Epigenetics refers to heritable changes in gene expression not involving alterations to the gene sequence. Epigenetic modifications can repress tumor suppressor genes, and, unlike DNA mutations, may be reversed by targeting the enzymes involved. Derepression of tumor suppressor genes can lead to reversal of malignant cell behavior in vitro, and may be associated with a clinical effect in cancer patients. Vidaza has been shown to reverse the effects of DNA hypermethylation with subsequent tumor suppressor gene re-expression and likewise MGCD0103 has been shown, in vivo, to reverse the effects of cancer-associated deacetylation resulting in gene expression reactivation.

About MDS

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. The majority of patients with high-risk MDS eventually experience bone marrow failure, which can cause bleeding and infection that lead to death.

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 the 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).

Vidaza is believed to exert its antienoplastic 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 Pharmion

Pharmion is a biotechnology company focused on acquiring, developing and commercializing innovation 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, 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 difference include the outcome of ongoing clinical trails, 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 Corporation

CONTACT: Anna Sussman, Director, Investor Relations and CorporateCommunications of Pharmion Corporation, +1-720-564-9143

Web site: http://www.pharmion.com/

Source: PRNewswire-FirstCall

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