Celsion Corporation Issues Letter to Stockholders
CEO Provides Updates on Phase III OPTIMA Study Data Analysis and ThermoDox® Investigator-Sponsored Studies
To My Fellow Stockholders:
In response to the recent inquiries that we are receiving, I’d like to provide you with the following update regarding the OPTIMA Study’s ongoing analysis of probable futility findings, and ThermoDox®, generally.
As I have indicated in earlier press announcements and conference calls, since the unblinding of the OPTIMA Study at the second preplanned interim data analysis on
At the second interim analysis by the independent Data Monitoring Committee (DMC), which covered 80% of the deaths needed for the final analysis, indicated that the OPTIMA Study had narrowly crossed the futility boundary of
In our preliminary evaluation of the topline data,
What steps are we taking?
Also as promised, and in parallel, the Company has submitted all OPTIMA Study clinical trial data to the
- A Cox Regression Analysis for single solitary lesions including minimum burn time per tumor volume, evaluating similarities to the hypothesis generated from the
NIHpaper published in the Journal of Vascular and Interventional Radiology, available here, in which the key finding was that increased RFA heating time per tumor volume significantly improved overall survival in patients with single lesion HCC who were treated with RFA plus ThermoDox®, compared with patients treated with RFA alone. The completed HEAT Study subgroup finding upon which the OPTIMA Study design is based was consistent with the Company’s own results, which defined the optimized RFA procedure as a 45-minute treatment for tumors with a diameter of 3 centimeters.
- A site-by-site evaluation for RFA heating time-based anomalies that may have contributed to the treatment arm performance.
- An image-based evaluation comparing results from the OPTIMA Study to the data from the HEAT Study that led to the RFA heating time hypothesis.
We expect to report findings from these independent statistical analyses before the end of the year, either or both of which will guide our decision to continue to follow patients to the final analysis at 197 or more deaths, a milestone that should be reached sometime in mid-2021.
The DMC’s recommendation on
Investigator-Sponsored Studies with ThermoDox®
I also would like to update you on the multiple requests we are receiving from investigators to include ThermoDox® in their own studies involving several clinical indications. Below are summaries of several investigator-sponsored studies:
Oxford Universityplans to begin enrolling patients in a Phase I pancreatic cancer study with ThermoDox® in combination with High Intensity Focused Ultrasound(HIFU) in early 2021. The primary objective of this trial, known as the PanDox Study: Targeted Doxorubicin in Pancreatic Tumors, is to quantify the enhancement in intratumoral doxorubicin concentration when delivered with ThermoDox® and HIFU, versus doxorubicin monotherapy. This study is being undertaken pursuant to promising data in a mouse model of pancreatic cancer, which was published in the International Journal of Hyperthermiain 2018. That preclinical study showed a 23x increase in intratumoral doxorubicin concentration with ThermoDox® + HIFU, compared with a 2x increase in intratumoral doxorubicin concentration with free doxorubicin plus HIFU.
Utrecht Universityin the Netherlandscontinues to enroll patients in a Phase I breast cancer study to determine the safety, tolerability and feasibility of ThermoDox® in combination with Magnetic Resonance Guided High Intensity Focused Ultrasound(MR-HIFU) hyperthermia and cyclophosphamide therapy for the local treatment of the primary tumor in metastatic breast cancer (mBC). This investigator-sponsored study, which is being funded by the Dutch Cancer Society, the Center for Translational Molecular Medicine(a multi-million dollar public-private partnership in the Netherlands), will be conducted at University Medical Center Utrechtand will enroll up to 12 newly diagnosed mBC patients. Celsionwill supply Thermodox® clinical product for the trial.
- As evidence of the ongoing support
Celsionenjoys from the NIH, they have organized a clinical project to evaluate ThermoDox® plus the chemotherapy drug mitomycin in bladder cancer. Depending on the NIHtimelines, this study may commence as early as 2021.
A Final Comment
In the meantime, we are heartened by multiple requests from investigators to include ThermoDox® in their own studies involving a number of clinical indications. We believe this interest in investigator-sponsored trials reflects support for the potential of ThermoDox® despite the confounding findings from the OPTIMA Study second preplanned interim analysis.
While we await the outcome of additional data analyses from the OPTIMA Study, we continue to enroll patients in the Phase II portion of the OVATION 2 study evaluating GEN-1 for the treatment of advanced ovarian cancer. We expect patient enrollment in this clinical trial to be completed by the end of the second quarter of 2021.
Thank you for your continued interest in
Chairman, President and CEO
Celsion’s most advanced program is based on a 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.
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