Confidence has been high, even before July DMC review:
CEO letter
June 18, 2012
Dear Fellow Shareholders,
This is a great time for Celsion… I'm please to report that your Company has never been so well positioned.
The HEAT Study, our Phase 3 pivotal trial, combining the first drug on our elegant tumor targeting platform, ThermoDox®, with radio frequency ablation (RFA) to treat hepatocellular carcinoma (HCC) is fully enrolled. We are now looking forward to data, by our best calculations in the 4th quarter of this year, from the largest pivotal trial ever conducted in the intermediate stage of the largest unmet need in oncology. We have the financial resources sufficient to see us through data and well beyond.
And…If we are right; we have every reason to believe that we will be bringing to market one of the most important new drugs in a generation, ThermoDox®. Will the data be positive???...We have no reason to believe that it won't be. I don't want to suggest that we have had any peeks at the data, because we have not. We remain blinded; the integrity of the trial depends on that.
What we do know is that:
Doxorubicin, the cytotoxic agent in ThermoDox®, is active in liver cancers,
RFA delivers a lethal blow to HCC lesions, but efficacy is limited in larger tumors,
Combining these two powerful treatments in early clinical studies has shown remarkable results, and
The timeframe projected for data, 380 PFS events, is reasonably consistent with the assumptions that we made in constructing the HEAT Study
In addition, our Investigators, who include some of the leading KOL's in primary liver cancer, remain enthusiastic about the trial and the promise of ThermoDox®; we await results with great optimism.
I also want you to know that we have conducted our research with a great deal of care.
Among our clinical research institutions are some of the leading liver cancer centers in the world,
All of our institutions are highly qualified to conduct Phase 3 clinical trials,
Our Data Monitoring Committee has a roster of some of the most respected names in clinical oncology, and pays close attention, to among other things, data quality in its very frequent reviews of unblinded data,
Our Clinical Trial Quality Program relies on verification and rechecking source and case reported data - We expect no surprises,
Progression Free Survival (PFS), our agreed radiologic end point is determined by a central core lab, read twice, not once, and
Our visits and interactions with investigators are frequent and regular. We know virtually all 79 PI's personally.
We are well positioned…no surprises.
Our work is of vital importance. The HEAT Study has been designated a Priority Study by the NIH; one of 8 among the hundred or so enrolling patients…and the only one evaluating a 1st line therapy. If we are right, we enter the market alone as a 1st choice for non-resectable disease. Is the world watching? ….You bet it is. The FDA among 10 other regulatory agencies around the world has given us every benefit possible for a speedy and successful trial because, as you know, the statistics are sobering.
Liver cancer is being described as a future epidemic in many populations and, as such, it is critical that the HEAT Study provide a rigorous data set to support ThermoDox's broad, global use. The incidence of primary liver cancer today is approximately 26,000 to 28,000 cases per year in the United States, approximately 40,000 cases per year in Europe and is rapidly growing worldwide at approximately 750,000 cases per year, due to the high prevalence of Hepatitis B and C in developing countries. By 2020, the World Health Organization estimates that primary liver cancer may become the #1 cancer worldwide, surpassing lung cancer.
The global importance of establishing an effective treatment for primary liver cancer cannot be overstated. Clinical outcomes in this disease remain poor, with the 5-year survival rate at less than 10 percent and median survival from time of diagnosis at approximately 30 months. Cure, usually through surgery, is possible in fewer than 20 percent of patients.
Consistent with our global regulatory strategy, we plan to address as many markets as possible with the HEAT Study. We have worked closely with regulators in ten countries around the globe to ensure that it meets their standards for regulatory review and approval, particularly in the Asia Pacific region where the incidence of hepatitis B, a leading cause of liver cancer, is widespread. Most recently, in April 2012 we announced that study enrollment in China has now reached the minimum 200 patient requirement necessary to support registrational filing in this important country, where over 50 percent of the 750,000 global incidences of HCC occur. The HEAT Study has also enrolled a sufficient number of patients to support registrational filings in South Korea and Taiwan, two other large and important markets for ThermoDox®.
In December 2011, we received confirmation from the European Medicines Agency (EMA) that the HEAT Study, if successful, would be acceptable as the basis for regulatory submission in Europe. Not only does this decision give us a clear regulatory path in this major market, it provides the basis for other international filings in countries that require approval from a globally-recognized regulatory agency. The EMA's decision provides us with a second avenue for such recognition, further de-risking the ThermoDox® global regulatory strategy.
Further supporting our regulatory goals are a number of important designations for ThermoDox® and the HEAT Study, including Fast Track designation and 505(b)(2) agreement with the U.S. FDA, providing for a rolling NDA submission, a 6-month regulatory review and a simplified review process. ThermoDox® has been granted orphan drug designation in both the U.S. and Europe and the HEAT Study is also being conducted under an FDA Special Protocol Assessment.
While primary liver cancer is a priority for Celsion, ThermoDox®'s unique properties support its potential use beyond this indication. We have initiated the ABLATE Study, a multi-center Phase II randomized, double blinded study that is expected to enroll up to 88 patients with colorectal cancer metastasized to the liver (CRLM). Patients will be randomized to receive either RFA plus ThermoDox® or RFA alone for the treatment of their liver metastases. The primary study endpoint is based on one year local tumor recurrence, with secondary endpoints of time to progression and overall survival.
Our objective is to have CRLM data for presentation in a timeframe that follows closely the approval of ThermoDox® for HCC, with the intent that our clinical evidence will support compendia listing and expanded use of RFA + ThermoDox® to treat liver metastases, a market in the US and Europe that is 10 times that of HCC with an estimated 140,000 new cases each year in the United States alone. Up to 25 percent of patients with colorectal cancer present with liver metastases and another 50 percent develop liver metastases within 5 years. Unresectable liver metastases frequently represent a very poor prognosis. Because RFA is both efficacious and accepted local treatment modality for this disease, a rational strategy is to attempt to increase its efficacy for medium and large CRLM tumors with an adjunct such as ThermoDox®.
In 2011, Celsion strengthened its balance sheet by raising approximately $58 million in aggregate gross proceeds through the completion of several equity financing transactions. These financings largely eliminate our near-term reliance on the capital markets and provide us with the operating horizon to fund the Company into the 3rd quarter of 2013, runway sufficient to announce top-line data and evaluate our strategic and financial options for bringing ThermoDox® to market - all from a position of fiscal strength.
As a mature Phase III drug candidate, ThermoDox® also remains an attractive asset to potential partners. We will continue to evaluate geographic partnerships throughout the world to support the commercial launch of ThermoDox®, as we did in Japan, on very attractive terms. We have the resources to wait for the right deal at the right time. This, in turn, will deliver maximum value to our shareholders.
It gives us great pride to see the continued dedication and enthusiasm of our key research leaders, our partners, our employees, and our collaborators. We thank them and you, our investors, for your continued support.
Sincerely,
Michael H. Tardugno
President and CEO
