Celsion Corporation (NASDAQ:CLSN) announced publication of the manuscript, “Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions,” in Clinical Cancer Research, a high impact, peer-reviewed medical journal. The article reports on one of the largest controlled studies in hepatocellular carcinoma (HCC). It provides a comprehensive review of ThermoDox®, 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 and includes results from computer simulation studies and includes interesting findings from a post hoc subgroup analysis, all of which are consistent with each other and which — when examined together — suggest a clearer understanding of a key ThermoDox® 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: ThermoDox, when used in combination with Radiofrequency Ablation (RFA) standardized to a minimum dwell time of 45 minutes (sRFA ≥ 45 min), may increase the overall survival (OS) of patients with HCC. The lead author is Won Young Tak, M.D., Ph.D., Professor Internal Medicine, Gastroenterology & Hepatology, Kyungpook National University Hospital Daegu, Republic of Korea, and there are 22 HEAT Study co-authors along with Nicholas Borys, M.D., Celsion’s senior vice president and chief medical officer.
To test and confirm the HEAT Study post hoc subgroup analysis, Celsion is conducting 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 researchers, and statistical and regulatory experts, and based on extensive analysis of prior clinical and preclinical studies of ThermoDox® plus standardized RFA, the OPTIMA Study is 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.
Global interest in ThermoDox as a potential treatment option for HCC was recently showcased in the Company sponsored R&D Day held in New York City on October 12, 2017. Lead OPTIMA Study clinical investigators representing various geographical regions (Asia-Pacific and Europe) and multiple medical disciplines (hepatology, interventional radiology and surgery) presented their past and current experiences with ThermoDox for the treatment of primary liver cancer. The final 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 provided an average 58% improvement in OS compared to standardized RFA alone. The Hazard Ratio (HR) 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 years) 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 months for the standardized RFA only group.
“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 in the newly published article in the peer reviewed journal, Clinical Cancer Research, demonstrate that ThermoDox® plus standardized 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., 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.”
In August 2017, the OPTIMA Study’s Independent Data Monitoring Committee (IDMC), comprised 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. The Company announced that enrollment in the OPTIMA Study is 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 IDMC. 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.“There is an urgent need for new and better treatment options for HCC, the third leading cause of cancer in the world. We believe strongly that ThermoDox® may be an important new approach for the treatment of HCC. We are now fully committed to the OPTIMA Study and to learning more about how this combination therapy of standardized RFA plus ThermoDox® may significantly prolong the survival of, if not cure, patients suffering from this extremely deadly cancer,” stated Michael H. Tardugno, Celsion’s chairman, president and chief executive officer, in response to the article’s publication. “Supported with an independent endorsement by the National Institutes of Health, the OPTIMA Study and ThermoDox® may prove to be the most important oncology research in a generation,” Mr. Tardugno added.On November 29, 2016, the Company announced results from an independent retrospective analysis conducted by the National Institutes of Health 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.“We are highly focused on successfully executing the ongoing OPTIMA study,” stated Nicholas Borys, Celsion’s chief medical officer. “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, and to accomplishing our chief goal, the delivery of ThermoDox® as a novel, first-line treatment to HCC patients worldwide.”
Shares of Celsion are currently trading at $4.44, up $0.29 or 6.95%. CLSN has a 1-year high of $16.38 and a 1-year low of $1.24. The stock’s 50-day moving average is $2.24 and its 200-day moving average is $1.55.
On the ratings front, Maxim analyst Jason McCarthy upgraded CLSN to Buy, with a price target of $7, in a report issued on October 4. The current price target represents a potential upside of 69% from where the stock is currently trading. According to TipRanks.com, McCarthy has a yearly average return of 5.8%, a 45% success rate, and is ranked #911 out of 4697 analysts.
Celsion is an oncology drug development company. It focuses on developing a portfolio of innovative cancer treatments, including directed chemotherapies, DNA-mediated immunotherapy and RNA- based therapies. The company’s products include ThermoDox and GEN-1. Celsion was founded by Yim-Pan Cheung in 1982 and is headquartered in Lawrenceville, NJ.