Inability of Pixantrone to Form Toxic Iron Complexes Results in Significant Reduction in Cardiac Cell Toxicity Compared to Currently Marketed Anthracyclines
NEW ORLEANS, Dec. 8 /PRNewswire-FirstCall/ -- Cell Therapeutics,
Inc. ("CTI") (Nasdaq and MTA: CTIC) announced today an abstract to
be published online at the journal Blood website by M. Hacker, et
al. demonstrating significant reduction in cardiac cell toxicity
with pixantrone compared to currently marketed anthracyclines. The
authors conclude that the reduction is due to pixantrone's
inability to generate toxic drug iron complexes and reduced
propensity to generate oxygen free radicals. Pixantrone was
specifically designed to have a higher affinity and avidity for the
topisomerase II enzyme, which is the common target for this class
of anti-cancer agents, while reducing oxygen-free radicals and
preventing the formation of toxic drug metal complexes, which are
the primary culprit that leads to dose-related irreversible heart
damage associated with standard anthracyclines.
"This study adds to the growing scientific evidence which is
central to the mechanistic basis for the relatively low incidence
of cardiac events observed in our pixantrone clinical trials
compared to the expected incidence of events had other
anthracyclines been used. The ability to reintroduce an effective
anthracycline like agent to patients who are no longer eligible to
receive further standard anthracycline therapy due to potential
irreversible heart damage addresses a major and growing unmet
medical need," Jack Singer, M.D., Chief Medical Officer of Cell
Therapeutics, Inc.
About the Study
To validate the proposed mechanisms underlying the observed
differences in cardiotoxicity, researchers used established
spectrophotometric techniques to quantify iron and drug
interactions that are thought to be mechanistic for chronic
doxorubicin cardiotoxicity. When adding increasing amounts of iron
to drug solutions, they observed that doxorubicin and mitoxantrone
underwent changes in visible range absorbance patterns, which is
characteristic of the drug to iron complex formation, confirming
the expected 1:3 Fe(II)-drug ratio for both doxorubicin and
mitoxantrone. In contrast, no spectrophotometric changes were
observed with iron added to pixantrone, clearly demonstrating that
pixantrone does not bind iron. In vitro studies using H2C9 rat
myocardial cells indicate that pixantrone (ID50 >50 ug/ml) is
far less toxic than doxorubicin (ID50= 1 ug/ml). Moreover,
pixantrone does not induce significant reactive oxygen species
(ROS) production in the H2C9 cells compared to doxorubicin.
About Pixantrone
Pixantrone (BBR 2778), is a novel topoisomerase II inhibitor
with an aza-anthracenedione molecular structure that differentiates
it from the anthracyclines and other related chemotherapy agents.
Anthracyclines are the cornerstone therapeutic for the treatment of
lymphoma, leukemia, and breast cancer. Although they are
sufficiently effective to be used as first-line (initial)
treatment, they cause cumulative heart damage that may result in
congestive heart failure many years later. As a result, there is a
lifetime limit of anthracycline doses and most patients who
previously have been treated with an anthracycline are not able to
receive further anthracycline treatment if their disease returns.
It also can be administered through a peripheral vein rather than a
central implanted catheter as required for other drugs in this
class. Pixantrone has been granted fast track status
designation.
About Cell Therapeutics, Inc.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.
This press release includes forward-looking statements that
involve a number of risks and uncertainties, the outcome of which
could materially and/or adversely affect actual future results and
the trading price of the securities of CTI. Specifically, the risks
and uncertainties that could affect the development of pixantrone
include risks associated with preclinical and clinical developments
in the biopharmaceutical industry in general, and with pixantrone
in particular, including, without limitation, the potential failure
of pixantrone to prove safe and effective for the treatment of
relapsed or refractory, aggressive non-Hodgkin's lymphoma as
determined by the U.S. Food and Drug Administration, the potential
failure of pixantrone to significantly reduce cardiac cell toxicity
compared to currently marketed anthracyclines, the potential
failure of pixantrone to reintroduce an effective anthracycline
like agent in patients, CTI's ability to continue to raise capital
as needed to fund its operations, competitive factors,
technological developments, costs of developing, producing and
selling pixantrone, and the risk factors listed or described from
time to time in CTI's filings with the Securities and Exchange
Commission including, without limitation, CTI's most recent filings
on Forms 10-K, 10-Q and 8-K. Except as may be required by law, CTI
does not intend to update or alter its forward-looking statements
whether as a result of new information, future events, or
otherwise.
Posted: December 2009