I am holding shares of Celsion (NASDAQ:CLSN) up to and through the end of January 2013, when we can expect the company to announce results of its phase III clinical trial. I will illustrate why the trial should be a success and why you might consider holding through the catalyst as well.
HEAT Study Phase III
ThermoDox with RadioFrequency Ablation (RFA) in Treatment of Hepatocellular Carcinoma. Initiated in February 2008, the trial was designed to test the effectiveness of ThermoDox in conjunction with RadioFrequency Ablation as an effective treatment for liver cancer.
ThermoDox is the love child of Celsion's patented lysolipid thermally sensitive liposome technology and Doxorubicin (a common chemotherapeutic drug). Or if you prefer, Doxorubicin wrapped in fat.
RadioFrequency Ablation is the process of eradicating material using high frequency currents and is a common procedure for tumor reduction and removal. The procedure is usually either percutaneous or laproscopic and has the added benefit of working well in conjunction with cytotoxic drugs. Recent improvements in the administration of RFA should make a minor contribution towards increasing efficacy and decreasing side effects reported during the trial.
During treatment the patient is hooked to an IV through which he or she is administered either 50mg/m2 ThermoDox or placebo. Approximately 15 minutes after beginning the IV doctors proceed with ablation. Heat from an alternating radio current increases temperatures of the tumor and surrounding cells to around 42 degrees Celsius. The elevated temperature increases cell porosity and heat sensitive Doxorubicin is released into the targeted areas.
Indications of Success
Curiously, one of the most compelling reasons why ThermoDox should succeed is often absent from any discussion of how effective the drug will prove.
Data presented in March of 2008 to the Society of Interventional Radiology definitively indicates an increase in size of the effective area of treatment when ThermoDox is administered in conjunction with RadioFrequency Ablation. In other words, the addition of ThermoDox, on average, has increased the volume of the lesion resulting from RFA by 43.3%.
For the relevance of that bit of data I direct you to the January 2002 issue of the American Journal of Roentgenology. In a study titled "Percutaneous Radiofrequency Ablation of Hepatic Tumors During Temporary Venous Occlusion," the good doctors indicate:
A major limiting factor is the maximal size of the radiofrequency lesion that can be induced with a single probe placement. Because the ideal tool would have to create, in a single delivery of radiofrequency, an area of destruction measuring 0.5-1 cm larger than the targeted tumor (in a manner akin to surgical margins) and because the largest area of destruction that can be obtained in clinical practice with commercially available systems with single probe placement and radiofrequency delivery is roughly 4-5 cm in diameter..
[ Am. J. Roentgenol. May 1, 2006 186:S269-S274]
Both studies are interesting if you are at all curious about the mechanisms by which ThermoDox achieves success. I encourage you to spend some time browsing through them.
Some analysts hold the opinion that as investors we are unable to gain insight into the efficacy of ThermoDox because insufficient clinical data exists. What I found to be true however was quite the contrary. A great deal of previous research is available from which we can gauge the likelihood of ThermoDox success.
In May 2005 the Radiological Society of North America published the results of a study which concluded that RadioFrequency ablation in conjunction with Doxorubicin "may be useful for treatment of large tumors and [in] achieving an ablative margin within the untreated tissue surrounding RF ablation-treated tumors."[Radiology May 1, 2010 255:2 405-414]
Don't forget, ThermoDox is Doxorubicin. It is simply wrapped in a little fat blanky and packaged nicely for the FDA to approve as an effective treatment for HCC.
Next I found a similar study from the National Center for Biotechnology Information, published October of 2011, which verified the efficacy of Doxorubicin + RFA treatment and concluded the treatment "improved tumor growth control and decreased viable tumor compared with other therapies. " [Radiology. 2011 Dec;261(3):813-23. doi: 10.1148/radiol.11110361. Epub 2011 Oct 24.]
There are more studies out there, but for the most part they are consistent in indicating that Doxorubicin + RFA provide a relatively effective treatment for cancer tumors.
ThermoDox Phase I trial data
Next I'd like to take a look at data from the actual phase I trial of ThermoDox in order to see what, if any, conclusions can be drawn.
In his article "Celsion's HEAT Study: A far from Certain Outcome," Biotech Sage provides an analysis of data he presents in a chart labeled "time to progression by cohorts."
Using the same set of data from which he drew a negative conclusion of ThermoDox, I found a most simple and blunt affirmation of Thermodox's efficacy. The affirmation comes in the form of dose response. Biotech Sage ignores the scaffold on which we see days to progression climb from 32 days all the way up to 185 days as the dosage of ThermoDox administered is increased from 20mg to 50mg. We would NOT see this progression if ThermoDox were not effective PERIOD.
Primary liver cancer vs. metastasized cancers
Although I believe ThermoDox is an effective treatment for primary liver cancer (originated in the liver), it is not as effective for patients with cancers which have metastasized to the liver.
Celsion has effectively isolated those patients which should respond best to ThermoDox + RFA for this phase III trial.
Parameters for participation in the HEAT trial:
- Inclusion criteria includes: Diagnosed hepatocellular carcinoma.
- Exclusion criteria excludes: extrahepatic metastasis.
The trial was designed with success in mind.
I'd like to take a moment to make a less scientific and more personal stab at one of Adam Feuerstein's articles I found regarding Celsion's ThermoDox.
The National Cancer Institute states with regards to adult primary liver cancer ,"The prognosis for any treated primary liver cancer patient with progressing, recurring, or relapsing disease is poor." I'll put it to you bluntly, any relatively safe drug or treatment which proves even marginally more effective in treating liver cancer will be deemed a success namely by the FDA, by investors, and especially by those suffering from liver cancer.
ThermoDox was created for the purpose of improving longevity and decreasing toxicity and it will not fail simply because tumors often grow back in other parts of the liver. We measure success by improved efficacy, not by absolute and permanent remission. You must either disregard large swaths of data or rearrange the conventional definition of success in order to come to a conclusion that ThermoDox will fail.
I encourage you to spend time digging through existing clinical trial data relative to Doxorubicin and RadioFrequency Ablation as well as the ThermoDox phase I trial results. I am optimistic about the future of ThermoDox and believe that with positive phase III results we should see a dramatic increase in Celsion share prices.