Pharmion Corporation
(Nasdaq: PHRM) 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 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.