Lately I've been sizing up why Celsion's (CLSN) HEAT phase III clinical trial will succeed. Coupled with that, the chart speaks for what may be coming. Of course, the fiscal cliff is creating an over-sold situation.
Within weeks, Celsion will report on its HEAT phase III clinical trial for hepatocellular carcinoma in the liver. While some invest based on the market, it makes much more sense to keep your nose buried in the veracity of Celsion's Thermodox science. Continual study has resulted in an air-tight explanation explaining how the clinical trial design is heavily weighted in Celsion's favor.
To summarize: It all comes down to tumor or lesion size. As it currently stands radiofrequency ablation [RFA] is ineffective against tumors in the 3-7 cm range; tumors in the 5-7 cm range even more so. Recurrence is very high and very near term and long-time survival equally unlikely. Meaning, Celsion has designed its trial for the placebo arm to fail. Enter Thermodox. In contrast, it is well-established that RFA plus Thermodox widens the kill zone of tumors. Meaning, Celsion has designed its trial for RFA plus Thermodox to succeed. In the rest of this article, this thesis will be explained in greater detail.
Primary Assertion for Success
The reason RFA plus Thermodox will report successful phase III primary results is because the HEAT trial design requires at least one lesion "No more than 4 HCC lesions with at least one ≥ 3.0 cm and none > 7.0 cm in maximum diameter, based on diagnosis at screening" and "If a subject has a large lesion (5.0 - 7.0 cm), any other lesions must be less than 5.0 cm." Next, it will be explained why the trial design strongly favors Thermodox's success.
[HCC = hepatocellular carcinoma]
Support for the Primary Assertion
The context for the following four points is derived from Dr. Poon's presentation at the 2012 Annual Congress of the Cardiovascular and Interventional Radiological Society of Europe.
1. There are no current satisfactory treatments for patients with hepatocellular carcinoma in the liver with measured lesions/tumors in the 3-7 cm range. That is the lesion target range in the HEAT phase III study. RFA alone, the placebo arm, is destined to fail. Recurrence and survival rates are dramatically shortened in patients with tumors > 5 cm. This is an established fact: Liver cancer is the Grim Reaper of cancers. Celsion's placebo arm, RFA alone, has a long history of failure.
2. The HEAT phase III study is a two arm comparison of (1) RFA alone, versus (2) RFA plus Thermodox in at least one cancerous lesion(s) in the range of 3-7 cm. The key for investors weighing their investment decision in Celsion is grasping the fact that RFA alone in lesions in the range of 3-7 cm, especially in tumors > 5 cm, is not curative. This is why Celsion could predict so precisely the timeframe for the clinical trial. There are hundreds of cases documenting the time-frame of tumor recurrence (See Dr. Poon's presentation).
3. Only RFA plus Thermodox offers the potential to totally destroy lesions in the range of 3-7 cm because of the wider margin of the treatment. This is why Celsion is betting on an improved recurrence rate and ultimately overall survival with the addition of Thermodox. Celsion has plenty of data and sixty plus years of doxorubicin's history of being an effective cancer killing agent if it can be delivered in high concentrations. That is exactly what Thermodox with RFA is designed to do.
4. The ingenuity of the HEAT phase III trial design is that Celsion has chosen with the FDA, EMA, and Asian authorities' approval to match their treatment regimen of RFA plus Thermodox against RFA alone in a particular tumor size range. Why the FDA, EMA, and Asian authorities would agree to this is quite simple: there is no current satisfactory treatment for people with tumors in the 3-7 cm range especially > 5 cm. No doubt this is why Thermodox was granted Orphan Drug status and is being Fast-Tracked by the FDA because there is no other satisfactory treatment for liver cancer patients with deadly tumors of this size.
While there are bulls and bears on both sides of the upcoming January 2013 HEAT phase III results, clearly investors are anxious to weigh the risk. Upon failure, a nosedive in the share price below $2/share is inevitable. But upon success, given Thermodox's global opportunity and its multiple Thermodox footprint in the company's pipeline, $20-$50/share appears to be a conservative target for 2013. After all, this would be a first-line treatment for hepatocellular carcinoma liver patients with tumors in the 3-7 cm range, and obviously, Thermodox could be used in lesions that are smaller.
While investors want to hear and read both sides of the HEAT trial's potential outcome, the study's trial design tips the scale in Thermodox's favor. It is also explains why the company has been so good in predicting the clinical trial's completion date knowing the short recurrence rate in patients receiving RFA treatment alone. In fact, the short case argument actually lends further support to the thesis that RFA alone is a miserable failure because it is incapable of adequately eradicating cancerous cells in tumors in the range of 3-7 cm and that information is documented in hundreds of cases across multiple clinical trials.
So where is the stock price heading prior to the HEAT study's outcome? Great question. Of late the short bearish case has been winning the day. Nevertheless, investors will need to form their own opinions, but the more I study Thermodox and understand the clinical trial design, my expectation is it will succeed primarily because RFA alone is known to be a miserable failure in tumors in the 3-7 cm range.
Quite frankly, the present situation of the bull-bear case with Thermodox reminds me of a similar situation I encountered with Acadia's (ACAD) Pimavanserin clinical trial. When I understood how Acadia had fine-tuned the clinical trial in favor of Pimavanserin success, I withstood a general market sentiment that Pimavanserin would fail. I see the same thing happening here with Celsion's Thermodox. While its mechanism of releasing a concentrated amount of doxorubicin with RFA treatment is not hard to understand, the probability of success is the tumor size target identified by the clinical study. Given that there is ample evidence that the addition of Thermodox expands the kill-zone (doxorubicin's sixty year history of killing cancer cells), it is just as logical to postulate that in larger size tumors (inadequate for RFA alone) Thermodox increases the ablation zone and in turn improves the time to recurrence and overall survival.
So irrespective of what the shorts and bears are doing to tear down Celsion's chances, I will take what I learned from Acadia's Pimavanserin drug trial and apply it Celsion's Thermodox. I maintain a strong buy.
Additional disclosure: Investors buy and/or sell at their own risk. This article is for entertainment purpose only and offers zero individual advice. You are duly warned and obligated to seek the advice of a licensed market professional. 'Long' for me is until I sell and I do not 'short' stocks. I may sell and/or buy any stock at any time.