Celsion Corporation Reports Preclinical Results of ThermoDox® for the Treatment of Bladder Cancer Published in the Internati...
April 13 2017 - 8:30AM
Higher Concentrations of Doxorubicin Accumulation
and Distribution within the Bladder Wall Were Achieved with
ThermoDox® Combined with Mild Local Hyperthermia Compared to Free
Doxorubicin Alone
Celsion Corporation (NASDAQ:CLSN) today announced publication
of the article, “Lyso-Thermosensitive Liposomal Doxorubicin for
Treatment of Bladder Cancer,” in the International Journal of
Hyperthermia. The article describes the results of porcine in vivo
studies to evaluate ThermoDox® in combination with loco-regional
mild hyperthermia for targeted drug delivery to the bladder wall as
a potential treatment for bladder cancer. Swine bladder walls
are similar in proportion and composition to human bladders.
Doxorubicin accumulation and distribution within the bladder wall
with ThermoDox® plus mild bladder hyperthermia was achieved at
concentrations nearly ten times higher than with free intravenous
doxorubicin combined with mild bladder hyperthermia. The study was
conducted under a Cooperative Research and Development Agreement
(CRADA) with the National Institutes of Health (NIH) to evaluate
whether ThermoDox® combined with mild heating of the bladder can
target drug delivery in the bladder.
It is estimated that over 79,000 new cases of
urinary bladder cancer will be diagnosed in the United States in
2017 and over 16,800 people will die of the disease during this
same period. Approximately 70 percent of new cases of bladder
cancer present with non-muscle invasive disease and are typically
treated by a technique called transurethral resection of the
bladder which removes as much of the tumor as possible.
However, 40 percent of patients with high risk non-muscle invasive
disease experience a recurrence and another 33 percent experience
disease progression. To reduce this high rate of recurrence,
intravesical (in the bladder) therapy is used. Intravenous
administration of free doxorubicin is commonly used as part of an
effective standard perioperative chemotherapy regimen for muscle
invasive disease; however results with intravesical doxorubicin
have been less effective presumably from inability to deliver
doxorubicin across the bladder urothelium (epithelial surface of
the bladder).
The NIH studies were conducted under the
direction of Dr. Bradford Wood, MD, Director, NIH Center for
Interventional Oncology and Chief, NIH Clinical Center
Interventional Radiology. The results of the studies are summarized
below:
• Range of doxorubicin concentrations from the urothelium to the
serosa (outer surface of the bladder):
- 20.32 – 3.52 ug/g for ThermoDox® + hyperthermia (HT)
- 2.34 – 0.61 ug/g for free doxorubicin + hyperthermia
- 2.18 – 0.51 ug/g for ThermoDox® with no hyperthermia
• Average doxorubicin concentrations in the
urothelium/lamina:
- 9.7 +/- 0.67 ug/g for ThermoDox® + hyperthermia (HT)
- 1.2 +/- 0.39 ug/g for free doxorubicin +
hyperthermia
- 1.15 +/- 0.38 ug/g for ThermoDox® with no hyperthermia
• Average doxorubicin concentrations in the muscularis:
- 4.09 +/- 0.81 ug/g for ThermoDox® + hyperthermia (HT)
- 0.86 +/- 0.24 ug/g for free doxorubicin +
hyperthermia
- 0.62 +/- 0.15 ug/g for ThermoDox® with no hyperthermia
Computational model results were similar to the
measured doxorubicin levels and suggest that adequate temperatures
were reached within the bladder for drug release from the
lyso-thermosensitive liposomal doxorubicin, ThermoDox®.
"The incomplete response of bladder tumors to
intravesical drugs, like doxorubicin and mitomycin C, has been
attributed in part to inadequate drug delivery and poor penetration
across the urothelium resulting in sub-therapeutic drug
concentrations in the bladder wall,” said Dr. Bradford Wood, MD,
Director, NIH Center for Interventional Oncology and Chief, NIH
Clinical Center Interventional Radiology. “To address this
limitation, one promising strategy to enhance the permeability of
the bladder wall to improve the efficacy of intravesical
chemotherapy is the use of hyperthermia to stimulate the release of
chemotherapeutic agents from thermosensitive nanocarriers for
patients who have failed standard first line therapy for bladder
cancer.”
“The NIH’s continued research interest in
ThermoDox® and its application in the treatment of many difficult
to treat cancers underscores the significance of ThermoDox’s
potential and its unique means of locally concentrating doxorubicin
in a highly effective way,” said Michael H. Tardugno, Celsion's
chairman, president and chief executive officer. “This study not
only reinforces ThermoDox’s mechanism, it provides further
assurance that the conclusions from the NIH’s independent analysis
of ThermoDox® plus radio frequency ablation for the treatment of
primary liver cancer are based on a broad set of clinical and
preclinical evidence. The data presented by the NIH at the
2016 RSNA Annual Meeting in November 2016 showed that the longer
the target tissue is heated, the greater is the clinical
benefit. Multiple experiments conducted by Celsion suggest
that this is the result of increased doxorubicin tissue
concentration, and we believe provides strong validation for our
ongoing global Phase III OPTIMA Study in primary liver
cancer. A successful OPTIMA Study will provide the means to
expand ThermoDox’s utility for patients with bladder cancer.”
About ThermoDox®
Celsion's most advanced program is a
heat-mediated, tumor-targeting drug delivery technology that
employs a novel heat-sensitive liposome engineered to address a
broad range of difficult-to-treat cancers. The first application of
this platform is ThermoDox®, a lyso-thermosensitive liposomal
doxorubicin (LTLD), whose novel mechanism of action delivers high
concentrations of doxorubicin to a region targeted with the
application of localized heat at 40°C, just above body temperature.
ThermoDox® has the potential to address a broad range of
cancers.
Celsion's LTLD technology leverages two
mechanisms of tumor biology to deliver higher concentrations of
drug directly to the tumor site. In the first mechanism, rapidly
growing tumors have leaky vasculature, which is permeable to
liposomes and enables their accumulation within tumors. Leaky
vasculature influences a number of factors within the tumor,
including the access of therapeutic agents to tumor cells.
Administered intravenously, ThermoDox® is engineered with a
half-life to allow significant accumulation of liposomes at the
tumor site as these liposomes recirculate in the blood stream.
In the second mechanism, when an external heating device
heats tumor tissue to a temperature of 40°C or greater, the
heat-sensitive liposome rapidly changes structure and the liposomal
membrane selectively dissolves, creating openings that can release
a chemotherapeutic agent directly into the tumor and into the
surrounding vasculature. Drug concentration increases as a function
of the accumulation of liposomes at the tumor site, but only where
the heat is present. This method damages only the tumor and the
area related to tumor invasion, supporting more precise drug
targeting.
About Celsion Corporation
Celsion is a fully-integrated oncology company
focused on developing a portfolio of innovative cancer treatments,
including directed chemotherapies, immunotherapies and RNA- or
DNA-based therapies. The Company's lead program is ThermoDox®, a
proprietary heat-activated liposomal encapsulation of doxorubicin,
currently in Phase III development for the treatment of primary
liver cancer and in Phase II development for the treatment of
recurrent chest wall breast cancer. The pipeline also
includes GEN-1, a DNA-based immunotherapy for the localized
treatment of ovarian and brain cancers. Celsion has two
platform technologies for the development of novel nucleic
acid-based immunotherapies and other anti-cancer DNA or RNA
therapies.
The Company has a Cooperative Research and
Development Agreement (CRADA) with the NIH. Any reference to
NIH should not be viewed as an endorsement or a recommendation of
Celsion, its products or services. For more information on
Celsion, visit our website: http://www.celsion.com.
(LTSL/ThermoDox®, HEAT Study/HCC, OPTIMA Study/HCC)
Celsion wishes to inform readers that
forward-looking statements in this release are made pursuant to the
"safe harbor" provisions of the Private Securities Litigation
Reform Act of 1995. Readers are cautioned that such
forward-looking statements involve risks and uncertainties
including, without limitation, unforeseen changes in the course of
research and development activities and in clinical trials; the
uncertainties of and difficulties in analyzing interim clinical
data, particularly in small subgroups that are not statistically
significant; FDA and regulatory uncertainties and risks; the
significant expense, time, and risk of failure of conducting
clinical trials; the need for Celsion to evaluate its future
development plans; possible acquisitions or licenses of other
technologies, assets or businesses; possible actions by customers,
suppliers, competitors, regulatory authorities; and other risks
detailed from time to time in the Celsion's periodic reports and
prospectuses filed with the Securities and Exchange
Commission. Celsion assumes no obligation to update or
supplement forward-looking statements that become untrue because of
subsequent events, new information or otherwise.
Celsion Investor Contact
Jeffrey W. Church
Sr. Vice President and CFO
609-482-2455
jchurch@celsion.com
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