Ongoing Phase III Trial to Confirm Hypothesis
That The Combination of Standardized Radio Frequency Ablation
(sRFA) Plus Lyso-Thermosensitive Liposomal Doxorubicin (LTLD) May
Substantially Increase Survival of Patients with HCC Compared to
sRFA Alone
Celsion Corporation (NASDAQ:CLSN) today announced publication of
the article, “RFA plus lyso-thermosensitive liposomal doxorubicin:
In search of the optimal approach to cure intermediate-size
hepatocellular carcinoma,” in Hepatic Oncology, a peer-reviewed
medical journal. The article provides a comprehensive overview of
the clinical evaluation conducted to date of lyso-thermosensitive
liposomal doxorubicin (LTLD), Celsion’s proprietary heat-activated
liposomal encapsulation of doxorubicin, for the treatment of
primary liver cancer, also known as hepatocellular carcinoma or
HCC. The article details learnings from the Company’s 701 patient
HEAT Study, a computational modeling study, an experimental animal
study and the HEAT Study post hoc subgroup analysis, all of which
are consistent with each other and which -- when examined together
-- suggest a clearer understanding of a key LTLD heat-based
mechanism of action: the longer the target tissue is heated, the
greater the doxorubicin tissue concentration. Additionally,
the article explores a new hypothesis prompted by these findings:
LTLD, when used in combination with Radio Frequency Ablation (RFA)
standardized to a minimum dwell time of 45 minutes (sRFA > 45
min), may increase the overall survival (OS) of patients with HCC.
Written by Riccardo Lencioni, MD and Dania Cioni, MD of the
Sylvester Comprehensive Cancer Center, University of Miami Miller
School of Medicine in Miami, Florida, the article is published in
the June 10, 2016 issue of the journal, Hepatic Oncology.
“There is an urgent need for new and better
treatment options for HCC, the sixth most common cancer in the
world, and the third most common cause of death from malignant
disease,” noted Michael H. Tardugno, Celsion's chairman,
president and chief executive officer, in response to the article’s
publication. “We believe strongly that ThermoDox® may be an
important new approach to the treatment of HCC. We are also
now committed to learning more about how an LTLD regimen may
prolong the survival of patients suffering from this extremely
deadly cancer,” Mr. Tardugno added.
Interest in ThermoDox® as a potential treatment
option for HCC increased markedly among liver cancer experts
worldwide following the announcement by Celsion in July 2015 of the
latest OS analysis of the HEAT Study post hoc subgroup.
According to this announcement, this most current OS analysis
demonstrated that in a large, well bounded, subgroup of patients
(n=285 patients, 41% of the previous 701 patient HEAT Study),
treatment with a combination of ThermoDox® and standardized RFA
(defined as Radio Frequency Ablation standardized to a minimum of
45 minutes or sRFA>45 min) provided an average 58% improvement
in OS compared to standardized RFA alone. The Hazard Ratio (HR) at
this analysis is 0.63 (95% CI 0.43 - 0.93) with a p-value of
0.0198. In this large subgroup, median OS for the ThermoDox®
plus standardized RFA group translates into a 25.4 month (more than
2.1 year) survival benefit over the standardized RFA only group –
totaling approximately 80 months (6-1/2 years, which is considered
a curative treatment for HCC) for the ThermoDox® plus standardized
RFA group versus 53.6 months for the standardized RFA only
group.
Note: As discussed in the Hepatic Oncology article, the
hypothesis tested in the HEAT Study was that ThermoDox® would
produce a therapeutic doxorubicin tumor concentration when combined
with the normal practice of RFA, thereby expanding the ‘treatment
zone’ and targeting any micro-metastases outside the so-called
‘ablation zone.’ The criterion for RFA use in the HEAT Study
was limited to ablation of each target lesion plus a 360° 1-cm
margin, however; it included no attempt to manage RFA approach or
RFA dwell time, despite the essential role of heat in the LTLD
mechanism of action.
To test and confirm this most current HEAT Study
post hoc subgroup analysis, Celsion initiated the Phase III OPTIMA
study, a global, pivotal, double-blind, placebo-controlled clinical
trial (Clinical Trials.gov NCT021126560). Developed in consultation
with leading primary liver cancer, statistical and regulatory
experts, and based on extensive analysis of prior clinical and
preclinical studies of ThermoDox® plus standardized RFA, the OPTIMA
study is now evaluating ThermoDox® in combination with RFA
standardized to a minimum of 45 minutes across all investigators
and sites for treating lesions 3 to 7 centimeters, versus
standardized RFA alone.
“We are highly focused on successfully executing
the ongoing OPTIMA study, the only global study in HCC,” Mr.
Tardugno stated. “We look forward to sharing our progress with the
scientific community as we continue to advance this program, and to
accomplishing our chief goal, the delivery of ThermoDox® as a
novel, first-line treatment to HCC patients worldwide.”
The OPTIMA Study
OPTIMA, a pivotal, double-blind,
placebo-controlled Phase III clinical trial, is expected to enroll
up to 550 patients at up to 75 sites in the North
America, Europe, China and Asia
Pacific. As of June 2016, the study has been successfully
enrolling patients at more than 50 clinical sites in 13 different
countries in North America, Europe and Asia
Pacific. In December 2015, Celsion announced that it had
received a Clinical Trial Application (CTA) approval from
the China Food and Drug Administration (CFDA) to conduct
the OPTIMA Study at up to 20 additional clinical sites
in China, the country where approximately 50% of the 850,000
new cases of primary liver cancer are diagnosed each year and where
the Company aims to enroll more than 200 patients in
the China territory, the minimum number required by the
CFDA to file a New Drug Application (NDA), assuming positive
clinical results.
The primary endpoint for the OPTIMA Study is
overall survival (OS). The statistical plan calls for two interim
efficacy analyses by an independent Data Monitoring Committee
(iDMC). The design of the OPTIMA Study is supported by the
retrospective analysis of a large subgroup of 285 patients in the
Company's previous 701 patient HEAT Study in primary liver cancer.
The study is also designed to establish a clear path to approval in
major liver cancer markets worldwide, with results from the OPTIMA
Study, if successful, providing the basis for a global registration
filing and marketing approval.
About LTLD (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, LTLD, 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 with a half-life to allow
significant accumulation of liposomes at the tumor site as these
liposomes recirculate in the blood stream. The second: When
an external heating device heats the 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 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 damages only the tumor and the area related to tumor
invasion, supporting 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 anticancer DNA or RNA therapies, including TheraPlas™ and
TheraSilence™. For more information on Celsion, visit our website:
http://www.celsion.com. (CLSN-TD CLSN-HS CLSN-OS)
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
Celsion Media Contacts
Harriet Shelare
Director, Communications
860-483-1721
hshelare@celsion.com
Bill Berry
Berry & Company
212-253-8881
bberry@berrypr.com
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