Pharmion Corporation
(Nasdaq: PHRM) announced that the U.S. Food and Drug Administration
(FDA) has granted Fast Track designation for oral Azacitidine in the
treatment of Myelodysplastic Syndromes (MDS).
Fast Track programs are designed to facilitate the development and
expedite the review of new drugs that are intended to treat serious or
life-threatening conditions and that demonstrate the potential to address
unmet medical needs. Fast Track emphasizes the critical nature of close,
early communication between the FDA and sponsors. The benefits of Fast
Track include scheduled meetings to seek FDA input into development plans,
and the option of submitting a New Drug Application in sections rather than
all components simultaneously. These meetings can help the FDA and sponsors
reach early agreement on design of the clinical efficacy studies that will
be needed to support approval.
The FDA stated that Fast Track designation was granted for oral
Azacitidine for MDS because Azacitidine is approved to treat all subtypes
of MDS, and because it will potentially provide a safer, more comfortable,
more convenient and more efficient route of administration of Azacitidine.
"We are extremely enthusiastic about working closely with Pharmion to
drive the development of oral Azacitidine," said Dr. Hagop Kantarjian,
chair of the department of leukemia at the University of Texas M.D.
Anderson Cancer Center. "Vidaza has now demonstrated a unique and profound
survival benefit in higher-risk MDS, and we think oral Azacitidine may
provide significant benefit in treating lower risk forms of MDS as well. We
are delighted that the FDA shares our view that its development should be
expedited. The opportunity to explore the biological and clinical
consequences of continuous oral dosing of Azacitidine is particularly
exciting, since we know that DNA remethylation occurs between cycles of
intermittent parenteral therapy. Effects of continuous Azacitidine dosing
on tumor RNA, another potential azacitidine target, will also be explored
for the first time."
Pharmion currently markets the parenteral formulation of azacitidine,
known as Vidaza(R) (azacitidine for injection) for the treatment of
patients with Myelodysplastic Syndromes (MDS). In January 2007 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. Earlier this month, Pharmion announced topline results from the
largest study ever conducted in higher-risk MDS, which demonstrated a
significant improvement in survival for patients treated with Vidaza. In
the primary endpoint analysis, Vidaza treatment was associated with a
median survival of 24.4 months versus 15 months for those receiving
conventional care regimens, an improvement of 9.4 months (p
Pharmion is exploring oral Azacitidine's utility in the treatment of
MDS and other cancers where demethylation may provide an anti-tumor effect.
Oral Azacitidine is the subject of a Phase 1 multi-center, open label dose
escalation trial that will assess the maximum tolerated dose, dose limiting
toxicities and safety of a seven day, multi-cycle oral dosing regimen of
oral Azacitidine in patients with MDS and AML. In addition, the trial will
examine pharmacokinetics and pharmacodynamic effects of orally administered
Azacitidine, as compared with parenteral Vidaza.
An oral dosage formulation of Azacitidine, in addition to the more
desirable and convenient route of administration, would enable the
evaluation of a low-dose regimen that could maximize demethylation and gene
re-expression, as well as the evaluation of long-term or maintenance
therapy.
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 Epigenetics
DNA methylation and histone deacetylation are two of the more studied
epigenetic regulators of gene expression. Epigenetics refers to changes in
the regulation 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 have
been demonstrated in vitro and in vivo in hematological malignancies and in
solid tumors. Vidaza has been shown to reverse the effects of DNA
hypermethylation with subsequent gene re-expression and likewise MGCD0103
has been shown, in vivo, to reverse the effects of inappropriate
deacetylation resulting in gene expression reactivation. 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.
About Pharmion
Pharmion is a leading global oncology 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, which
express the current beliefs and expectations of management, including
statements related to the potential efficacy of oral Azacitidine and
Vidaza. Such statements are based on current expectations and beliefs only
and are subject to risks and uncertainties, many of which are beyond our
control, which could cause the actual results to differ significantly from
the results expressed or implied by such statements. Actual results could
differ materially depending on a number of factors, and we caution
investors not to place undue reliance on the forward-looking statements
contained in this press release. Important factors that could cause or
contribute to such differences include, but are not limited to, the
potential failure of product candidates, including oral Azacitidine, to
demonstrate safety and efficacy in clinical and non-clinical testing; the
possibility that topline results from the clinical trial discussed in this
press release will not be confirmed upon full analysis of the results of
the trial and that additional information relating to the safety, efficacy
or tolerability of Vidaza may be discovered upon further analysis of data
from that trail or analysis of data from other ongoing Vidaza clinical
trials; the ability to complete regulatory submissions and gain regulatory
approvals in a timely manner; the ability to initiate and complete trials
at the referenced times; the impact of competition from other products
under development by Pharmion's competitors; the uncertainty of the
regulatory environment and changes in the health policies of various
countries; uncertainties regarding market acceptance of products newly
launched, currently being sold or in development; and the failure of
third-party manufacturers to produce the product volumes required on a
timely basis. 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 June 30, 2007,
its Annual Report on Form 10-K for the year ended December 31, 2006 and in
our 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 Corporation
pharmion
View drug information on Vidaza.