OPTIMA Study Enrollment is Approaching 70%
Independent Data Monitoring Committee Provided Unanimous Recommendation to Continue Study in August
2017
Investigators Meetings in Thailand and China Attended by 70% of Investigators in China and
Asia-Pacific
LAWRENCEVILLE, N.J., Sept. 27, 2017 (GLOBE NEWSWIRE) -- Celsion Corporation (NASDAQ:CLSN), an oncology drug
development company, today provided a detailed update for the Company's 550 patient, multinational, double-blind,
placebo-controlled, pivotal Phase III clinical study of ThermoDox® in combination with radiofrequency ablation (RFA) for primary
liver cancer (the OPTIMA Study) which include recent investigators meetings in Bangkok, Thailand and Shanghai, China. With the
growing incidence of primary liver cancer in China and Asia-Pacific, representing approximately 75% of the estimated 850,000 cases
diagnosed annually, this region represents a strategically important element of the Company’s global registration and
commercialization strategy for ThermoDox®.
The Company announced that enrollment in the OPTIMA Study is now approaching 70% of the 550 patients necessary
to ensure that its primary end point, overall survival, can be evaluated with statistical significance. The statistical plan for
the OPTIMA Study calls for two interim efficacy analyses by the independent Data Monitoring Committee (DMC). The Company currently
projects full patient enrollment by mid-2018 and the first pre-planned efficacy analysis after 118 overall survival events by the
first quarter of 2019.
“With independent confirmation by the NIH of the relationship between RFA heating time and the significant
impact that it has on overall survival when combined with ThermoDox®, OPTIMA Study investigators fully recognize the value of the
findings from the HEAT Study, reinforcing their interest and support for our highly de-risked, ongoing global Phase III OPTIMA
Study," said Michael H. Tardugno, Celsion's chairman, president and chief executive officer. "The previously announced unanimous
recommendation for study continuation by the independent Data Monitoring Committee was based on their review of all available
clinical data from 275 patients, and is further evidence of ThermoDox's recognized potential to provide a new and important first
line therapeutic option for patients with primary liver cancer."
The design of the OPTIMA Study is supported by a retrospective analysis of a large subgroup of 285 patients in
the Company's previous 701 patient HEAT Study in primary liver cancer. This subgroup of patients who received ThermoDox® plus
standardized RFA demonstrated a statistically significant improvement in survival of over two years compared to standardized RFA
alone. The median overall survival in the ThermoDox® plus standardized RFA arm was approximately 80 months (6 ½ years), which is
considered a curative treatment for primary liver cancer.
On November 29, 2016, the Company announced results from an independent retrospective analysis conducted by the
National Institutes of Health (NIH) on the intent-to-treat population of the 701 patient HEAT Study of ThermoDox® plus optimized
RFA for the treatment of primary liver cancer. The NIH analysis, which sought to evaluate the correlation between RFA burn
time per tumor volume (min/ml) and clinical outcome, concluded that increased RFA “burn time” per tumor volume significantly
improved overall survival (OS) in patients with solitary lesions treated with RFA + ThermoDox® compared to patients treated with
RFA alone. The NIH analysis included 437 patients with a single lesion from the Company’s HEAT Study, the same patient
population being treated in the Company’s ongoing Phase III OPTIMA study. The NIH findings are consistent with Celsion’s own
analysis of the HEAT Study data, which demonstrated that over a 3.5 year period, there was a statistically significant survival
benefit consistent with the HEAT Study in patients treated with ThermoDox® plus optimized RFA over the optimized RFA only
group.
In August 2017, the Company’s Data Monitoring Committee, comprised of an independent group of medical and
scientific experts who are responsible for reviewing and evaluating patient safety and efficacy data, completed a planned interim
analysis of the first 50% of patients randomized in the trial as of April 2017 and unanimously recommended that the OPTIMA Study
continue as planned based on the risk to benefit analysis by the Committee. The OPTIMA Study to date has accumulated data within
acceptable safety parameters.
"There is clear evidence that the duration of the RFA regimen is critical when treating patients with
ThermoDox®, and the totality of the data presented to date demonstrate that ThermoDox plus optimized RFA has a strong potential to
serve as a curative therapy for patients with liver cancer," said Professor Won Young Tak, M.D., Ph.D., Division of
Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu,
Republic of Korea and lead investigator in South Korea for the Company's HEAT and OPTIMA studies. "The OPTIMA Study is designed to
validate this approach in an indication where there exists a strong unmet need for effective treatment options."
Regulatory Strategy for ThermoDox®. ThermoDox® has received U.S. FDA Fast Track
Designation and has been granted orphan drug designation for primary liver cancer in both the U.S. and Europe. Further, the U.S.
FDA has provided ThermoDox® with a 505(b)(2) registration pathway. Subject to a successful trial, the OPTIMA Study has been
designed to support registration in all key primary liver cancer markets. Celsion fully expects to submit registrational
applications in the USA, Europe and China. The Company believes that applications will be accepted in South Korea, Taiwan and
Vietnam, three other large and important markets for ThermoDox® subject to approval in Europe, China or the USA.
“The Company’s optimism for Chinese registration is based on our multiple interactions with the China Food and
Drug Administration,” said Nicholas Borys, MD, Celsion’s senior vice president and chief medical officer. “During our December 2016
meeting with the Deputy Director of the Center for Drug Evaluation, Celsion presented the final overall survival data from the
Chinese patient cohort from the prior HEAT Study, which demonstrated a survival benefit in patients treated with ThermoDox plus
optimized RFA versus optimized RFA alone. The China only cohort was found to be consistent with the overall HEAT Study
findings. We were informed that if the ongoing Phase III OPTIMA trial is successful, the trial could serve as the basis for a
direct regulatory filing in China without the need to file for prior approval in the U.S. or the European Union. This would
allow the Company to accelerate its plans for a regulatory filing in China and, if approved, provide for a significantly earlier
launch date in China than originally expected,” noted Dr. Borys.
About the OPTIMA Study
The Phase III OPTIMA Study is expected to enroll up to 550 patients in up to 70 clinical sites in the United
States, Europe, China and Asia Pacific, and will evaluate ThermoDox® in combination with optimized RFA, which will be 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, which is supported by post-hoc analysis of data from
the Company's 701 patient HEAT Study, where optimized RFA has demonstrated the potential to significantly improve survival when
combined with ThermoDox®. The 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 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. 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, 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
