Celsion plans new late-stage trial of liver cancer drug ThermoDox based on data from study

Celsion plans new study of liver cancer drug

Celsion plans new late-stage trial of liver cancer drug ThermoDox based on data from study

Related Jan 2013 - Liver Cancer-Phase III HEAT trial of Thermodox Fails to Meet Goals

NEW YORK (AP) -- Celsion said Monday it wants to start another late-stage clinical trial of its liver cancer drug ThermoDox. 

The company said a year ago that ThermoDox did not meet its main goal in a clinical trial because it didn't improve their time to death or disease progression. Celsion said it is still following patients from that trial and said some may be living longer.

ThermoDox is heat-activated and is designed to deliver bigger doses of the chemotherapy drug doxorubicin directly to tumors. The trial compared a combination of ThermoDox and radiofrequency ablation, a treatment that uses heat to destroy unhealthy tissue, to radiofrequency ablation alone. Celsion said Monday that patients who received ThermoDox and at least 45 minutes of radiofrequency ablation appeared to live longer.

The Lawrenceville, N.J., company said it has been consulting with regulators and wants to start a new late-stage trial in the first half of 2014.

Read more...


January 27, 2014- Press release:
Celsion Corporation Announces Updated Overall Survival Results from Phase III HEAT Study of ThermoDox® in Primary Liver Cancer

Latest Data from Large Subgroup of Patients Shows that the Combination of ThermoDox® and Optimized RFA Provides a Statistically Significant Survival Improvement of Over 50%
Provides Basis for Further Development of ThermoDox® in HCC Patients

LAWRENCEVILLE, N.J., Jan. 27, 2014 /PRNewswire/ -- Celsion Corporation (NASDAQ: CLSN) today announced that the latest overall survival data from its post-hoc analysis of results from the Company's Phase III HEAT Study of ThermoDox®, Celsion's proprietary heat-activated liposomal encapsulation of doxorubicin in combination with radio frequency ablation (RFA), supports the continued clinical development of ThermoDox® in a prospective pivotal Phase III Study, subject to regulatory review and agreement. This analysis followed the announcement on January 31, 2013, that the HEAT Study did not meet its primary endpoint, progression-free survival (PFS). As provided for in the HEAT Study's Special Protocol Assessment (SPA) agreement with the U.S. Food and Drug Administration (FDA), the Company continues to follow patients for overall survival, the secondary endpoint of the Study. Data from four quarterly reviews of overall survival have been evaluated since the announcement of top line PFS data.

Data from the updated HEAT Study analysis suggests that ThermoDox® may significantly improve overall survival, compared to control, in patients whose lesions undergo RFA treatment for 45 minutes or more. These findings apply to patients with single HCC lesions (64.4% of the HEAT Study population) from both size cohorts of the HEAT Study (3-5 cm and 5-7 cm) and represent a subgroup of 285 patients (41% of the patients in the HEAT Study). Updated OS data from this subgroup of patients is summarized below:

In the patient subgroup treated in the ThermoDox® arm, whose RFA procedure lasted longer than 45 minutes (285 patients or 63% of single lesion patients) clinical results indicate a 55% improvement in overall survival, a Hazard Ratio of 0.64 (95% CI 0.41 - 1.00) and a P-value = 0.0495. Median overall survival for this subgroup has not yet been reached.

In contrast, the patient subgroup treated with ThermoDox® whose RFA procedure lasted less than 45 minutes in duration (167 patients or 37% of single lesion patients) indicated a Hazard Ratio of 1.12 (95% CI 0.68 - 1.86) and a P-value = 0.66. Median overall survival for this subgroup has not yet been reached.

The Hazard Ratios reported above warrants additional clinical development and should be viewed with caution since they are based on a retrospective analysis and the HEAT Study has not reached its median point for overall survival analysis. Celsion will continue to follow patients in the HEAT Study to the secondary endpoint, overall survival, and will update the subgroup analysis based on RFA heating duration.

"The HEAT Study post-hoc data is compelling. The combination of ThermoDox® and an optimized RFA treatment appears to have a significant improvement in overall survival in HCC patients," stated Dr. Nicholas Borys, Celsion's Chief Medical Officer. "While this conclusion is reached based on a post-hoc evaluation, it is nonetheless supported by the consistency of the data seen over a one year follow-up period, and by what is now a statistically significant outcome for overall survival. Our investigators are convinced that RFA can and should be optimized in future trials."

The HEAT Study and prior post-hoc analyses were presented at three medical conferences in 2013, including the World Conference on Interventional Oncology in May; the European Conference on Interventional Oncology in June and the International Liver Cancer Association Annual Conference in September. Presentations were made by some of the most highly recognized liver cancer researchers and key HEAT Study investigators. Quarterly overall survival data analyses have been conducted with the full support of these researchers and clinical investigators.

Additionally, Celsion has been consulting with its clinical advisors, regulatory and expert statistician consultants and the FDA regarding the study design and statistical plan for its proposed pivotal Phase III clinical trial. The Company anticipates initiating a multicenter global trial in the first half of 2014.

"These data continue to support our strong interest in ThermoDox® and its potential as a first line treatment for a significant percentage of the world's 750,000 newly diagnosed HCC patients," noted Michael H. Tardugno, Celsion's President and Chief Executive Officer. "In addition to the FDA, the Company is pursuing regulatory approval of its new Phase III clinical trial in multiple countries, particularly those where HCC's prevalence represents an important health issue. In parallel with this effort, we are recruiting key CRO partners to initiate the Study rapidly following regulatory agency agreement. With our strong financial resources and the support of the global HCC community, we are confident in our ability to conduct a timely and cash efficient pivotal program."

About Celsion Corporation
Celsion is dedicated to the development and commercialization of innovative cancer drugs, including tumor-targeting treatments using focused heat energy in combination with heat-activated liposomal drug technology. Celsion has research, license or commercialization agreements with leading institutions, including the National Institutes of Health, Duke University Medical Center, University of Hong Kong, the University of Pisa, the UCLA Department of Medicine, the Kyungpook National University Hospital, the Beijing Cancer Hospital and the University of Oxford. For more information on Celsion , visit our website: http://www.celsion.com.

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; HEAT Study data is subject to further verification and review by the HEAT Study Data Management Committee; the need for Celsion to evaluate its future development plans; possible acquisitions or licenses of other technologies, assets or businesses or the possible failure to make such acquisitions or licenses; 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.

Investor Contact
Jeffrey W. Church
Senior Vice President and
Chief Financial Officer
609-482-2455
jchurch@celsion.com

SOURCE Celsion Corporation

News Provided by Acquire Media
http://investor.celsion.com/releasedetail.cfm?ReleaseID=821197

Liver Cancer-Phase III HEAT trial of Thermodox Fails to Meet Goals

Investment Commentary

Celsion Liver Cancer Trial Fails to Meet Goals, Stock Plunges
Catherine Arnst1

In a major setback, Celsion (NASDAQ: CLSN), based in Lawrenceville, NJ, reported today that its lead drug candidate failed in a Phase III clinical trial for treatment of primary liver cancer. CEO Michael Tardugno told an investor conference call this morning that the result “was not even close” to meeting the trial’s goals.

Investor reaction was swift and furious, with Celsion’s share price dropping 80 percent in the first hour of trading, to $1.59 from the previous close of $8.02. Celsion’s stock had more than tripled in price over the prior year.

Celsion said that the Phase III HEAT trial of Thermodox—a proprietary reformulation of the chemo drug doxorubicin—in combination with radiation was designed to slow the cancer from spreading, a measure called progression free survival, by at least 33 percent compared with the control arm, but did not meet that goal. The trial results, Tardugno said, would not justify filing for approval in any country.

Part of the problem, Tardugno said, is that patients in the control arm did about 20 percent better on standard treatment than the company had projected. Cancer trials can sometimes take years to enroll patients and compile results from the time the trial design was approved, and during that time the standard of care continues to improve, making it more difficult for new treatments to show an advantage over existing therapies.

Celsion will continue to study the results to determine whether patients currently on Thermodox would be followed to determine whether the drug can extend overall survival.

The results were released just a week after the company announced a technology development deal for Thermodox in liver cancer with Zhejiang Hisun Pharmaceutical, a major Chinese drug company, that could have been worth up to $100 million over 10 years if the drug had succeeded. Celsion has already received an initial payment of $5 million from Hsuin, which Tardugno said the company is not required to give back the payment in light of the trial failure.

Tardugno sought to reassure investors by telling them the company has approximately $27 million in cash on hand as of today, enough money to fund its operations “well into 2014.”

Celsion’s drug technology, developed in partnership with Duke University, encases chemotherapy drugs in tiny bubbles called liposomes that are then activated by low levels of radiation to deliver their payload directly to cancer cells. Thermodox won fast-track designation from the Food & Drug Administration in August 2010 for development against primary liver cancer.

Celsion also has heat activated liposomes in Phase II clinical trials for breast cancer and a second form of liver cancer, but Tardugno said the company will have to give the latter trial “some consideration” before it decides whether or not to continue in light of the HEAT failure.

http://www.xconomy.com/new-york/2013/01/31/celsion-liver-cancer-trial-fails-to-meet-goals-stock-plunges/

Celsion plunges 80 percent as liver cancer therapy fails trial

Jan 31, 2013 11:36am EST
(Reuters) - Celsion Corp shares plunged by more than 80 percent after a late-stage study of the company's experimental liver cancer treatment ThermoDox failed to meet the main goal of increasing patients' survival without worsening their cancer.

The stock fell to a low of $1.41 before recovering slightly to trade at $1.46 on heavy volume on the Nasdaq on Thursday.

"I don't believe the data will support (marketing) registration in any of the major markets," Celsion Chief Executive Michael Tardugno said on a conference call.

The trial, named HEAT, consisted of 701 patients across 11 countries and was designed to show a 33 percent improvement in progression-free survival.

Celsion said it was conducting additional analyses of data from the trial to assess the future value of ThermoDox.

Patients on the control arm performed about 20 percent better than expected whereas those on ThermoDox performed worse than anticipated, Roth Capital Partners analyst Joseph Pantginis said, quoting the company.

"We are disappointed by the failure of the HEAT study and we highlight the increased risk around the company's pipeline which is driven by ThermoDox," he said.

ThermoDox is also being tested in mid-stage studies as a drug-delivery method for breast and colorectal cancers.

Celsion CEO Tardugno said the company will continue enrolling patients in the mid-stage breast cancer study.

ThermoDox utilizes a liposome -- a tiny bubble composed of lipids -- as a vehicle to transport a commonly used chemotherapy drug called doxorubicin, directly to the tumor.
Localized heat releases doxorubicin, depositing it in and around the tumor, maximizing the effect of the medication.

The liver-cancer study compared the HEAT results against patients treated with a procedure where tumors are destroyed using electricity, otherwise called radiofrequency ablation.
Pantginis downgraded Celsion's rating to "neutral" from "buy" and slashed his price target on the stock to $1.70 from $10, saying the target is now based solely on the mid-stage study of ThermoDox in breast cancer.

Celsion said it had sufficient cash to cover its expenses well into 2014. It has unaudited cash and investments of about $27 million.

CEO Tardugno said the company will review its colorectal cancer trial in the context of the HEAT results and then decide on whether to continue with the study.

(Reporting By Pallavi Ail in Bangalore; Editing by Roshni Menon and Sreejiraj Eluvangal)

http://www.reuters.com/article/2013/01/31/us-celsion-study-thermodox-idUSBRE90U0MI20130131

ThermoDox: Liver Cancer Treatment Is A '$1 Billion Drug,' Drugmaker Says

ThermoDox: Liver Cancer Treatment Is A '$1 Billion Drug,' Drugmaker Says

By Bill Berkrot

NEW YORK, June 19 (Reuters) - Michael Tardugno, chief executive of tiny Celsion Corp, is convinced he has a $1 billion cancer therapy on his hands with its ThermoDox treatment for liver cancer.

The company, with a market valuation of only about $70 million and all of 16 employees, is not trying to reinvent the wheel. But by placing a very old cancer drug - the chemotherapy doxorubicin - into a new delivery method and adding heat, Celsion believes it has a recipe for success that can address a large need in cancer.

"Certainly this is a $1 billion drug," Tardugno told Reuters in an interview.

"We don't bring the newest biotechnology to market in our drug system," he said. "We have the ability to take a very promising technology and apply it to an unmet medical need."

About 750,000 new cases of liver cancer are diagnosed each year. The World Health Organization has predicted that by 2020 liver cancer will surpass lung as the No. 1 cancer worldwide.

ThermoDox is intended for liver cancer patients not eligible for resection surgery.

Tardugno was not ready to predict multiple billions in annual sales just yet and noted that all, of course, depends on positive data from its pivotal late stage trial.

Celsion said it could have initial data from its Phase III trial of 700 patients with primary liver cancer by the end of this year. Given the priority status bestowed upon ThermoDox by health regulators in the United States and elsewhere, Celsion could have its first drug on the market in relatively short order.

"There's a chance if we execute perfectly here that we could be seeing an approval by the end of 2013," Tardugno said. "The FDA is giving us every chance possible for rapid trial, rapid reading of the results and a filing strategy that will allow us to bring an NDA (new drug application) to the agency very quickly."

The FDA and European regulators have agreed that a 33 percent improvement in the time it takes for the disease to worsen - progress-free survival (PFS)- is an approvable goal for Celsion's therapy in liver cancer. The company will also provide overall survival data when it becomes available.

Once the Phase III data is released, Celsion will be looking for licensing deals with other companies to sell ThermoDox in Asia, Europe and emerging markets.

"There's more than one multi-national company ... that have initiated diligence" regarding potential licensing deals, Tardugno said.

"We believe we can be the best stewards for ThermoDox in the United States," he said, but added that "positive data will inspire some very serious discussions about a license to the U.S. market."

The company is also testing ThermoDox in breast cancer that has spread to a patient's chest wall and in pancreatic cancer.

Celsion shares closed up 3.7 percent to $2.22 on Tuesday, after trading as high as $2.32.


TIGHT REIN ON CASH

When Tardugno become CEO five years ago, Celsion was a medical device company. He sold the device assets to Boston Scientific for about $40 million and used those funds to focus on new drug development.

The company has since sought to spend sparingly and efficiently. It is burning cash at a rate of about $5 million a quarter, which will allow it to complete the pivotal trial without raising more cash. It pays its contract manufacturer for ThermoDox according to production milestones, not time and materials, Tardugno said.

The company has also signed a supply agreement with China's Zhenjian Hisun Pharmaceutical Co to manufacture ThermoDox for China, where liver cancer is especially prevalent due to high rates of hepatitis. That deal gives Celsion regulatory exclusivity in China, which Tardugno sees as stronger than the country's patent protections.

As government health plans and private insurers scrutinize the costs of new drugs more closely, ThermoDox could prove to be relatively cost effective as it uses a generic medicine and is administered just once on an outpatient basis, Tardugno said.

ThermoDox encapsulates doxorubicin in a liposome, a type of fat bubble or vessel, that naturally makes its way to the liver after being introduced intravenously. A low level of heat is then applied directly to the cancerous lesion using a process called radiofrequency ablation.

Current treatment for liver cancer that has not spread might use ablation alone on small tumors. Adding the doxorubicin allows treatment of larger tumors because it expands the treatment area.

Celsion believes its unique delivery method can help avoid some of the serious side effects associated with doxorubicin, including heart problems.

"You can deliver a drug directly to a tumor in concentrations that if you had otherwise delivered this concentration systemically you'd kill the patient," Tardugno explained. (Reporting By Bill Berkrot; Editing by Michele Gershberg, Gary Hill and Gunna Dickson)

http://www.reuters.com/article/2012/06/20/us-celsion-thermodox-idUSBRE85J0RT20120620

Committee to Continue and Complete Phase III HEAT Study of ThermoDox(R) in Primary Liver Cancer as Planned

Celsion Announces Unanimous Recommendation by Independent Data Monitoring Committee to Continue and Complete Phase III HEAT Study of ThermoDox(R) in Primary Liver Cancer as Planned

28 Nov 2011
Company May Conduct Additional Interim Efficacy Analyses Following Agreement With FDA
Reconfirms 380 PFS Events Projected to Occur in Late 2012


LAWRENCEVILLE, NJ, USA I November 28, 2012 I Celsion Corporation (NASDAQ: CLSN - News), a leading oncology drug development company, announced today that the independent Data Monitoring Committee (DMC) for Celsion's Phase III HEAT Study, a multinational, double-blind, placebo-controlled, pivotal study of ThermoDox® in combination with radio frequency ablation (RFA) for hepatocellular carcinoma (HCC) or primary liver cancer, has completed a planned interim analysis for safety, efficacy and futility and unanimously recommended that the study continue to its final analysis as planned. The DMC evaluated data from 613 patients in its review, which was conducted following the realization of 219 progression-free survival (PFS) events within the study population. A total of 380 events of progression are required to reach the planned final analysis of the study.

Celsion also announced today that the DMC, in its review, followed a statistical boundary determined by the Company using the Lan DeMets implementation of the O'Brien-Fleming spending function. This approach allows for the Company to conduct additional interim efficacy analyses prior to final data read-out at 380 PFS events with no increased risk of statistical penalty. The additional analyses may allow for earlier stopping of the study. Additionally, based on its internally modeled estimates of PFS events, Celsion reconfirmed that 380 PFS events are projected to occur in late 2012.

"The DMC's unanimous recommendation is a significant achievement for Celsion based on the most comprehensive review of the HEAT Study to date, including the first-ever review of efficacy results," said Michael H. Tardugno, Celsion's President and Chief Executive Officer. "Critically, we have the potential to realize a successful outcome to the study prior to its planned completion. We are encouraged by what may be sufficient rationale for conducting an additional preplanned efficacy review prior to the 380 events called for in our protocol, and will seek to amend our Special Protocol Assessment Agreement with the FDA accordingly. We thank the DMC for their work and thorough review, and are grateful for the continued support and enthusiasm from the healthcare community, regulators, our investors and our employees."

The HEAT Study is being conducted under a U.S. Food and Drug Administration (FDA) Special Protocol Assessment, has received FDA Fast Track Designation and has been designated as a Priority Trial for liver cancer by the National Institutes of Health. Target enrollment of 600 patients was reached in August 2011, after which the DMC conducted this interim efficacy analysis based on the realization of 219 progression-free survival events. Consistent with the Company's global regulatory strategy, Celsion is continuing to enroll patients in the HEAT Study in order to randomize at least 200 patients in China, a requirement for sFDA (State Food and Drug Administration) registrational filing in that country and to ensure timely readout of final data. In addition to meeting the U.S. FDA enrollment objective, the HEAT Study has also enrolled a sufficient number of patients to support, in Asia, registrational filings in S. Korea and Taiwan, two very important markets for ThermoDox®.

About Primary Liver Cancer

Primary liver cancer is one of the most deadly forms of cancer and ranks as the fifth most common solid tumor cancer. The incidence of primary liver cancer today is approximately 26,000 cases per year in the United States, approximately 40,000 cases per year in Europe and is rapidly growing worldwide at approximately 700,000 cases per year, due to the high prevalence of Hepatitis B and C in developing countries. The standard first-line treatment for liver cancer is surgical resection of the tumor; however, 90% of patients are ineligible for surgery. Radio frequency ablation (RFA) has increasingly become the standard of care for non-resectable liver tumors, but the treatment becomes less effective for larger tumors. There are few non-surgical therapeutic treatment options available as radiation therapy and chemotherapy are largely ineffective in the treatment of primary liver cancer.

About ThermoDox® and the Phase III HEAT Study

ThermoDox® is a proprietary heat-activated liposomal encapsulation of doxorubicin, an approved and frequently used oncology drug for the treatment of a wide range of cancers. In the HEAT Study, ThermoDox® is administered intravenously in combination with RFA. Localized mild hyperthermia (39.5 - 42 degrees Celsius) created by the RFA releases the entrapped doxorubicin from the liposome. This delivery technology enables high concentrations of doxorubicin to be deposited preferentially in a targeted tumor.

For primary liver cancer, ThermoDox® is being evaluated in a 600 patient global Phase III study at 76 clinical sites under an FDA Special Protocol Assessment. The study is designed to evaluate the efficacy of ThermoDox® in combination with Radio Frequency Ablation (RFA) when compared to patients who receive RFA alone as the control. The primary endpoint for the study is progression-free survival (PFS) with a secondary confirmatory endpoint of overall survival. Additional information on the Company's ThermoDox® clinical studies may be found at www.clinicaltrials.gov.

About Celsion Corporation

Celsion is a leading oncology company dedicated to the development and commercialization of innovative cancer drugs including tumor-targeting treatments using focused heat energy in combination with heat-activated drug delivery systems. Celsion has research, license, or commercialization agreements with leading institutions such as the National Institutes of Health, Duke University Medical Center, University of Hong Kong, the University of Pisa, and the North Shore Long Island Jewish Health System.

SOURCE: Celsion