Celsion Corporation (NASDAQ:
CLSN), an oncology focused drug-development company, today
provided an update on its ongoing review of unblinded data from the
second pre-planned interim analysis of the global Phase III OPTIMA
Study of ThermoDox® in combination with radiofrequency ablation
(RFA) for the treatment of hepatocellular carcinoma (HCC), or
primary liver cancer. The Company announces it will continue
following patients for overall survival (OS), noting that the
unexpected and marginally crossed futility boundary, suggested by
the Kaplan-Meier analysis at the second interim analysis on July 9,
2020, may be associated with a data maturity issue. The Company
further notes that 26 consecutive patient deaths represented
exclusively in the second analysis behave far differently from the
balance of the patients who have died as of this date.
Removing the 26 consecutive patient deaths,
which occurred between September 2019 and March 2020, from the
pre-planned interim analysis suggests that the OPTIMA Study OS
pattern is similar to the prospective HEAT Study subgroup upon
which the OPTIMA Study is based, at the approximate comparable
point in time. In addition, subsequent to the second interim
analysis there were eight patient deaths in a 3:1 ratio of control
arm to treatment arm patients, which further supports a concern for
data maturity.
Celsion further noted that OPTIMA Study
investigators in China and Vietnam, who enrolled 37% of the
subjects, joined the study approximately 12 and 18 months,
respectively, after the trial was initiated. The Kaplan-Meier
curves for both geographies demonstrate a potential data maturity
issue when compared with the behavior of the HEAT Study subgroup
and other OPTIMA Study testing site regions. The China sites, in
particular, show a negative Kaplan-Meier curve, yet with a 56%
improvement in the treatment arm in the median time to death. The
Vietnamese sites show a marginal Kaplan-Meier benefit, yet with a
45% improvement in the median time to death. The Company believes
that this dichotomy must be reconciled, most probably with longer
follow up, before it can determine the study’s direction.
Additionally, Celsion has sent the trial data,
including Chemistry, Manufacturing and Controls data, to the
National Institutes of Health (NIH) for independent analysis. All
computed tomography (CT) scans are being prepared and will be sent
for NIH’s evaluation of progression-free survival (PFS). Depending
on the trends noted during the OS follow-up period, Celsion may
choose to discontinue the Study at any time.
On July 13, 2020 Celsion announced that the
independent Data Monitoring Committee (DMC) recommended that
Celsion should consider stopping the OPTIMA Study. Finding that the
pre-specified boundary for stopping the trial for futility of 0.900
was marginally crossed with an actual value of 0.903, the DMC left
the final decision up to the Company as the p-value of 0.524 for
this analysis provided uncertainty.
“Last month’s DMC recommendation to consider
discontinuation of the OPTIMA Study based on the 2nd interim data
was never anticipated, nor was it supported by the science,
independent clinical evaluation of the HEAT Study subgroup or
prospective preclinical research conducted by Celsion and our
consultants to support the OPTIMA Study. We believe, therefore,
that Celsion is obligated to undertake this rigorous evaluation of
the data and the trial’s recruitment trends,” stated Michael H.
Tardugno, Celsion’s chairman, president and chief executive
officer. “While the trial outcome as predicted by the second
interim analysis may not change, and as unlikely as it may be, in
the event we see substantial clinical benefit while continuing to
monitor patients, we will carefully review our options with the 14
regulatory agencies that have allowed the OPTIMA Study to be
conducted. We appreciate the ongoing support and confidence from
our research Investigators and clinical advisors.”
The OPTIMA Study is a global, randomized,
double-blind, placebo-controlled clinical trial assessing the
efficacy of ThermoDox® in combination with RFA, which was
standardized to a minimum of 45 minutes for treating patients with
a lesion 3-7 cm in size, versus standardized RFA alone. The OPTIMA
Study enrolled 554 patients at 65 clinical sites in North America,
Europe, China and Asia Pacific. In addition to the primary overall
survival endpoint, progression-free survival, time to disease
progression and safety are key secondary endpoints.
The statistical plan for the OPTIMA Study
included two interim efficacy analyses by the DMC. The first
interim analysis was announced in November 2019 following data lock
in August 2019 after the prescribed minimum number of 128 patient
events (deaths) was reached, and the second interim analysis was
conducted in July 2020 following data lock in April 2020 after the
prescribed minimum number of 158 events was reached.
About ThermoDox®
Celsion’s most advanced program is a
heat-mediated 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. ThermoDox® is positioned
for use with multiple heating technologies and has the potential to
treat of a broad range of cancers including metastatic liver,
recurrent chest wall breast cancer and non-muscle invading bladder
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 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 subject 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 development for other cancer indications. The
Company’s product pipeline also includes GEN-1, a DNA-based
immunotherapy for the localized treatment of ovarian cancer.
Celsion has two platform technologies for the development of novel
nucleic acid-based immunotherapies and other anti-cancer DNA or RNA
therapies.
Forward-looking Statements
Forward-looking statements in this news 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 or regulatory authorities; and
other risks detailed from time to time in the Celsion's periodic
filings 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 ContactJeffrey
W. ChurchExecutive Vice President and CFO609-482-2455
jchurch@celsion.com
Or
LHA Investor RelationsKim
Sutton Golodetz212-838-3777kgolodetz@lhai.com
# # #
Celsion (NASDAQ:CLSN)
Historical Stock Chart
From Aug 2024 to Sep 2024
Celsion (NASDAQ:CLSN)
Historical Stock Chart
From Sep 2023 to Sep 2024