Publication Highlights Phase I Data Supporting
Safety and Feasibility of Treatment with ThermoDox® and
Non-Invasive, Focused Ultrasound
Celsion Corporation (NASDAQ: CLSN), an oncology drug development
company, today announced that results from the Phase I TARDOX trial
of ThermoDox® conducted at the University of Oxford, United
Kingdom, were published in the peer-reviewed journal, Radiology.
The TARDOX trial evaluated the safety and efficacy of ThermoDox®,
Celsion’s proprietary heat-activated liposomal encapsulation of
doxorubicin, along with focused ultrasound for the treatment of
liver cancer. The article, titled, “Focused Ultrasound Hyperthermia
for Targeted Drug Release from Thermosensitive Liposomes: Results
from a Phase I Trial,” included an evaluation of the TARDOX results
and the safety, efficacy and utility of treatment with ThermoDox®
plus targeted, non-invasive hyperthermic ultrasound in patients
with solid liver tumors, with treatment plans based on
patient-specific modeling.
“The findings published in Radiology serve as a
companion paper to the groundbreaking work published by Lyons et al
in Lancet Oncology in July 2018. This work by the TARDOX team
at the Oxford University Institute of Biomedical Engineering
clearly demonstrated the local activity of ThermoDox® in liver
cancer. This is the first published study to evaluate
ThermoDox® as an effective therapeutic when combined with
high-intensity focused ultrasound (HIFU). The Radiology paper
is also accompanied by an editorial which highlights the
significance of utilizing HIFU and ThermoDox®. Namely, that
high concentrations of important drugs such as doxorubicin –
through ThermoDox - can be delivered locally and effectively,” said
Nicholas Borys, M.D., Celsion's senior vice president and chief
medical officer.“ While further studies are warranted, the medical
community has advocated for the use of ThermoDox® with focused
ultrasound for some time, and these observations support the
potential for focused ultrasound to expand the use of ThermoDox® to
the treatment of other types of cancer.”
A lysolipid thermally sensitive liposome
encapsulating the chemotherapy agent, doxorubicin, ThermoDox® is
designed to release targeted levels of doxorubicin into and around
liver tumors with heat activation. The Phase I TARDOX study
demonstrated that focused ultrasound exposure with ThermoDox®
resulted in increased chemotherapy concentrations within liver
tumors that were an average of 3.7 times greater than preheating
levels across all 10 patients in the study.
“This latest publication of ThermoDox® clinical
data emphasizes the significance and utility of its thermally
activated delivery system and the high level of interest and
support from the medical community for improved, targeted delivery
of therapeutically potent levels of chemotherapy in patients with
primary liver cancer, and potentially other cancers.
Consistent with the US National Institutes of Health’s findings,
Oxford’s clinical results add to the independent evidence of
ThermoDox®’s unique and potent anti-cancer mechanism of action,”
said Michael H. Tardugno, Celsion's chairman, president and chief
executive officer. “Moreover, the positive findings from the TARDOX
study showed the viability of focused ultrasound to deliver potent
levels of doxorubicin with ThermoDox®, suggesting that ThermoDox®
could also be successful when used in combination with other
heating mechanisms, beyond radiofrequency ablation (RFA). This
highly reassuring research fully supports our robust clinical
development program for ThermoDox® in combination with RFA. We are
looking forward to the first of two planned interim efficacy
analyses from our ongoing Phase III OPTIMA study in 556 patients in
mid-2019.”
The Phase I TARDOX study evaluated patients with
inoperable primary or secondary liver tumors who had previously
received chemotherapy. In this trial, 10 patients received a single
intravenous dose of 50 mg/m2 of ThermoDox®, and ultrasonic heating
of target tumors was monitored in six participants using a
minimally invasive temperature sensor, while four patients were
treated without real-time thermometry. Safety was assessed by
analysis of magnetic resonance imaging (MRI) and biopsy specimens
for evidence of thermal ablation, as well as adverse event
monitoring. There was no evidence of focused ultrasound-related
adverse effects, including thermal ablation.
Numerous studies have demonstrated that focused
ultrasound can be used to generate mild heating to facilitate the
release of drug cargoes from thermosensitive liposomes (TSLs). We
believe the TARDOX study is the world’s first Phase I clinical
trial aimed at evaluating the effect of doxorubicin released from
TSLs after focused ultrasound–induced mild hyperthermia. The study
presents a model for predicting the focused ultrasound treatment
parameters needed to attain mild hyperthermia and facilitate
doxorubicin release from TSLs. This model may improve the current
clinical use of hyperthermia by providing an alternative strategy
for treatment planning based on a thermal model rather than actual
thermometry, which is more invasive.
For all participants, CT images were used with
the patient-specific hyperthermia model in order to define focused
ultrasound treatment plans. Feasibility was assessed by comparing
model-prescribed focused ultrasound powers to those implemented for
treatment. The mean difference between predicted and implemented
treatment powers was -0.1 W ± 17.7 SD. We believe this is a
meaningful initial demonstration of the model providing accurate,
successful treatment parameters. In addition, these observations
support the potential for non-invasive hyperthermic ultrasound to
expand the use of ThermoDox® to the treatment of other types of
cancer.
The TARDOX study was carried out as a
multi-disciplinary collaboration between Celsion, the Oxford
University Institute of Biomedical Engineering, the Oncology
Clinical Trials Office (OCTO) and the Oxford University Hospitals
NHS Foundation Trust.
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
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.
In one of its most advanced applications, ThermoDox®, when combined
with radiofrequency thermal ablation (RFA), has the potential to
address a range of cancers. For example, RFA in combination with
ThermoDox® has been shown to expand the “treatment zone” with a
margin of highly concentrated chemotherapy when treating individual
primary liver cancer lesions. The goal of this application is to
significantly improve efficacy.
Celsion’s LTLD technology leverages two
mechanisms of tumor biology to deliver higher concentrations of
drug directly to the tumor site. The first: 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, LTLD
is engineered to allow significant accumulation of liposomes at the
tumor site at the time of radiofrequency ablation as these
liposomes recirculate in the blood stream. The second: When the
tumor tissue is heated to a temperature of 40°C or greater, the
heat-sensitive liposome rapidly changes structure and the liposomal
membrane selectively dissolves, creating openings that release the
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 targets only the tumor and the
area related to tumor invasion, supporting precise drug
targeting.
About the OPTIMA Study
The Phase III OPTIMA Study has enrolled 556
patients in over 60 clinical sites in the United States, Europe,
China and Asia Pacific, and will evaluate ThermoDox® in combination
with optimized RFA, which was standardized to a minimum of 45
minutes across all investigators and clinical sites for treating
lesions three to seven centimeters, versus optimized RFA alone. The
primary endpoint for the trial is overall survival. The OPTIMA
Study is supplemented by post-hoc analyses of data from the
Company's 701-patient HEAT Study in which optimized RFA
demonstrated the potential to significantly improve survival when
combined with ThermoDox®. The OPTIMA Study’s statistical plan calls
for two interim efficacy analyses by an independent Data Monitoring
Committee.
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. 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. For more information on Celsion, visit our
website: http://www.celsion.com. (CLSN-LTSL/ThermoDox® CLSN-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; 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 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.
ThermoDox® is a registered trademark of Celsion
Corporation.
Investor Contact
Argot Partners
Sam Martin
212-600-1902
Sam@argotpartners.com
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