BOULDER, Colo., April 23 /PRNewswire-FirstCall/ -- Pharmion Corporation today announced that the multi-center, open label Phase 1 clinical trial of single dose oral azacitidine in patients with MDS, AML and malignant solid tumors has been successfully completed, and the Company will be initiating the planned multi-dose Phase 1 trial. The first Phase 1 trial assessed the bioavailability and pharmacokinetics of escalating single doses of orally administered azacitidine, while exploring the preliminary safety and tolerability profile of the compound.
The second Phase 1 trial is a multi-center, open label dose escalation trial and will assess the maximum tolerated dose, dose limiting toxicities and safety of a seven day, multi-cycle oral dosing regimen of azacitidine in patients with MDS and AML. In addition, the trial will examine pharmacokinetics and pharmacodynamic effects of orally administered azacitidine, as compared with the FDA approved parenteral regimen, which is marketed by Pharmion as Vidaza(R) (azacitidine for injection). Pharmion intends to present pharmacokinetic data from the first Phase 1 study in a poster session at the Annual Meeting of the American Society of Clinical Oncology in June and additional Phase 1 data is expected to be presented later in the year.
“We are extremely pleased that we have been able to demonstrate oral bioavailability and move into the multi-dose stage of the Phase 1 development,” said Andrew Allen, MD, MRCP, Ph.D., Pharmion’s chief medical officer and executive vice president. “In particular, we are looking forward to examining the pharmacokinetic and pharmacodynamic profile of the drug as we plan for Phase 2 and registration studies.”
“The progress of oral azacitidine is extremely exciting as it allows for the possibility of sustained DNA demethylation in a convenient manner,” said Dr. Guillermo Garcia-Manero, Chief, Section of Myelodysplastic Syndromes, M.D. Anderson Cancer Center. “There is a substantial body of evidence that sustained DNA demethylation could impact many tumor types and possibly turn certain cancers into chronically managed diseases. We are very enthusiastic about testing this hypothesis with oral azacitidine.”
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, 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 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. Vidaza was approved for IV administration in January 2007.
About Epigenetics
Azacitidine 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 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.
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 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 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 biopharmaceutical 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, including statements related to Pharmion’s future development plans for oral azacitidine. These forward-looking statements express the current beliefs and expectations of management. Such statements involve a number of known and unknown risks and uncertainties that could cause Pharmion’s actual results and timing of events to differ significantly from those expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include the potential failure of product candidates to demonstrate safety and efficacy in clinical testing; the ability to complete and initiate trials at the referenced times; the ability to conduct clinical trials sufficient to achieve a positive completion; the uncertainty of the regulatory approval process; uncertainties regarding market acceptance of products newly launched, and other factors that are discussed under the heading “Risk Factors” and elsewhere 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: Breanna Burkart or Anna Sussman, Directors, Investor Relationsand Corporate Communications, Pharmion Corporation, +1-720-564-9150
Web site: http://www.pharmion.com/
