Pharmion Corporation
(Nasdaq: PHRM) today announced that the Investigational New Drug (IND)
application for the Company's oral formulation of azacitidine is now active
following its acceptance by the U.S. Food and Drug Administration (FDA).
The Company submitted the IND for oral azacitidine in December 2006.
Pharmion currently markets the parenteral formulation of azacitidine,
known as Vidaza(R) (azacitidine for injection) for the treatment of
patients with Myelodysplastic Syndromes (MDS). Earlier this week the FDA
approved a new drug application supplement to add intravenous use as a new
route of administration to instructions in the prescribing information for
Vidaza.
"DNA demethylating agents, like the approved parenteral formulation of
azacitidine, Vidaza, have been shown to be a safe and effective therapy for
MDS," said Andrew Allen, Pharmion's chief medical officer. "There is a
significant body of evidence that shows that the biological effects of
these agents may be improved or extended through sustained DNA
demethylation, which could most realistically be provided through oral
delivery. We are excited about testing this hypothesis in human clinical
studies and reinforcing our leadership in the development of epigenetic
anti-cancer therapies."
A Phase 1 study of oral azacitidine will be initiated shortly in
patients with MDS, acute myelogenous leukemia (AML) and malignant solid
tumors. The trial will assess the safety, tolerability, bioavailability and
pharmacokinetics of escalating single doses of orally administered
azacitidine.
"The opportunity to explore chronic administration of a DNA
hypomethylating agent with oral azacitidine is extremely exciting and may
lead to important changes in the way we think about combination therapies
as well as maintenance therapy after anti-cancer treatment," said Dr.
Guillermo Garcia-Manero, Chief, Section of Myelodysplastic Syndromes, M.D.
Anderson Cancer Center. "If successful, this could transform certain
cancers into chronically managed diseases."
Following this initial study, a multicenter, open label Phase 1 dose
escalation trial of orally available azacitidine will be initiated to
determine the maximum tolerated dose, dose limiting toxicities and safety
of a seven day oral dosing regimen of azacitidine in subjects with MDS or
AML. Pharmacokinetics and pharmacodynamic effects of the orally
administered azacitidine, as well as the FDA approved parenteral regimen,
will be compared.
Following the Phase 1 studies, if oral azacitidine demonstrates
adequate bioavailability, Pharmion will initiate a broad Phase 2 program in
solid and hematological tumors where hypermethylation is known to play a
role in tumor development and progression.
About Vidaza
On May 19, 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).
On January 29, 2007, the Company's new drug application supplement to
add intravenous (IV) use as a new route of administration to instructions
in the prescribing information for Vidaza was approved by the FDA. With
this approval, Vidaza may now be administered intravenously in a clinic or
hospital setting. With IV administration, the dosing for Vidaza remains the
same as the previously approved subcutaneous (SC) administration at 75
mg/m2 daily, for seven days, every four weeks.
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.
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 pharmion.
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
pharmion
View drug information on Vidaza.