CryoCor`s Cardiac Cryoablation System and the Clinical Trial for Atrial Fibrillation: Interview with Dr. Gregory Ayers, Found

First of all, I was very sorry to miss the presentation by former Senator Bill Bradley at CryoCor's kickoff meeting before the Boston Atrial Fibrillation meeting. What were some of the things he spoke about? For example, when was he diagnosed with AF? We brought Senator Bill Bradley in because we had been in contact for about a year, and as you may or may not be aware he suffers from atrial fibrillation (AF). As a result of his AF, he actually backed out of the democratic primary in 1999. Therefore, we brought Senator Bradley to the meeting to describe the impact of atrial fibrillation on his life to share with the investigators and research coordinators how his life had been substantially altered by having AF and how he has been treated medically along the way. He is hopeful that our atrial fibrillation clinical trial will be able to show a curative therapy that may help people like himself and have their AF cured and therefore no longer have it impact their life. At this meeting, the CryoCor Cardiac Cryoablation System, which is currently being evaluated in a FDA pivotal clinical trial, was also discussed. I want to talk about the trial as well, but first, please describe how the system works. There are three components of our system to treat AF in the electrophysiology lab. There is the console, which provides pre-cooled or liquid nitrous oxide to the catheter and controls its delivery to optimize the boiling process in the second component of the system, which is the disposable catheter. The disposable catheter transfers the liquid nitrous oxide to the tip of the catheter a metallic tip that serves as a boiling chamber for the nitrous oxide. When N2O boils at the tip of the catheter, we achieve -90 degrees Celsius, freezing the tissue. The catheter also is a conduit for removing the spent refrigerant, which is nitrous oxide in the gaseous state. The console then receives the spent gaseous nitrous oxide. The third component of the system is a sheath, which is a long tube that allows the EP physician to open and then maintain the opening of a small hole in the septum between the upper chambers (or atria) of the heart. Through that sheath, the physician is able to deliver our CryoCor CryoBlator catheter into the left atrium to deliver the therapy for AF. The sheath is not under the clinical trial, per se, as it is 510k cleared; what is actually being tested is the console and the catheter with the indication of treating atrial fibrillation. As I mentioned, the nitrous oxide boils in the tip of the catheter, under monitoring by the console to make sure that the boiling occurs under optimal conditions, to achieve and maintain the -90 degrees Celsius. The process is actually pulling heat from the tissue, freezing the cell. When the cells are frozen, you end up with an acellular region with normal protein structures, inhibiting electrical conduction of any impulses that would have passed through that area. Basically, to optimize this process, you have to first achieve a cold enough temperature to freeze the cell; equally as important is to maintain that temperature long enough to allow the cell to thoroughly freeze. How is the cryoablation system unique from other systems currently available? What makes our system unique is that we have the power to do what I mentioned. Independent of heat load, we can hit -90 degrees Celsius and hold this temperature because the console dynamically adjusts the driving pressure of the liquid nitrous. It is about thoroughly freezing the cell and what this results in is our system being considered a second-generation cryoablation system. This system is already CE Mark approved in Europe and has been commercially available for use there since 2002. What have been the success rates there? First, it is a limited commercial use to collect additional clinical data, both for publication and also because the clinical data from Europe has allowed us over the past couple of years to make critical modifications to our system. We wanted to make sure that the average user who is not being told exactly how to use the system, as is the case in a clinical trial, is able to use it and get adequate clinical results. Regarding the success rates, it is somewhat variable by arrhythmia. For atrial flutter and ventricular tachycardias, we see results that are at least comparable to radiofrequency (RF) ablation. While I can t make these statements as a specific claim, I can tell you that 15 centers in Europe that have been using our system say their procedure times are less, the patients do not feel pain, their fluoro time is reduced, and they feel that the procedure is safer with cryo. With respect to atrial fibrillation, our efficacy results are again at least equivalent to their experience with RF ablation. They see the same ability to diminish fluoroscopy time and diminish the pain to the patient during the application. The procedure times are equivalent to maybe slightly longer than RF procedures. Most importantly, they see no substantive complications associated with the use of cryo for AF ablation. We have not seen in the 500-600 patients treated in Europe over the past couple of years any substantial negative effects of cryo. We do not see stenosis, thromboembolic events, perforations, pericarditis, esophageal fistulas we see none of the complications that are associated with RF energy. It appears that since we do not affect extracellular proteins, we do not get a significant scarring effect we just get rid of the cells. How many patients are enrolled in the clinical trial so far? How many sites are involved? When did enrollment begin? The enrollment began in late December 2004. Over the period of December and early January, we had some sites with IRB approval to begin the study. We anticipate expanding that to 20-22 centers, similar to our flutter pivotal trial that we completed in early November of last year. Therefore, these additional centers are beginning to get IRB approval and are getting ready to start enrollment. How long will the trial go for? When do you think you might hear from the FDA about approval? Our anticipation is to complete enrollment in the year 2005, and then there is a 1-year follow-up period. I know we have not publicly disclosed the design of the study; the reason we have not disclosed it is because we are in what we believe to be a competitively advantaged position we are the only company enrolling today in a pivotal trial for AF, and for competitive reasons we do not want to disclose the design of our trial. So this trial for atrial fibrillation differs from the one that was done last year for atrial flutter? Correct. I can fully disclose the design of the atrial flutter trial; there were 160 patients enrolled at 22 sites. Those sites enrolled in the trial over a 10-month period of time, and enrollment was completed in late October. The atrial flutter trial has a six-month follow-up period. In addition, the trial design is identical to the most recently approved device from Biosense Webster for their cooled-tip RF catheter. Our results look very promising. We are in the process of filing our modules for the PMA and anticipate our final module will be filed in late June. We would anticipate approval for this indication by the end of this year or in the very early part of 2006. In addition, Dr. Ayers, your background in defibrillation technology is also quite extensive. I noticed that you previously worked for InControl, Inc., which developed the first implantable atrial defibrillator. I also read that you also hold 16 U.S. patents in the areas of defibrillation and cardiac arrhythmia management; could you describe some of these patents? The patents that I hold I think now number 18 I haven t fully disclosed my patents that are pending! My background encompasses both defibrillation and ablation. My PhD thesis work was in using ablation and evaluating the physiology and pathophysiology of ablation lesions. Specifically, the patents that I hold are in the area of atrial fibrillation detection, ventricular tachycardia and fibrillation detection, and in ways to deliver shocks for AF safely so that it does not induce other arrhythmias within its delivery. I also have patents in the area of patient s being able to control defibrillation shock delivery from implantable devices. Some of my recent patents are a little more out of line with defibrillation: I have a patent for a chest tube that is approved for cooling patients who undergo cardiac surgery, during the postoperative period, and I also have a patent for a sheath system that we utilize at CryoCor. What are some of the goals you have in mind for CryoCor for the future? What other developments or improvements in cryo would you like to see happen? Aside from launching our product in the US in 2006, if we receive regulatory approval: building a direct sales force and selling products. The other three areas of interest are further developing our existing catheter product line to add at least three additional products based on evolutionary changes to our catheter line based on our customer feedback from Europe and from the US clinical trial investigators. Therefore, we plan to look at a product line extension for the CryoBlator catheter over the next six to nine months. As far as the revolutionary, we are developing a catheter where a single catheter can be used to treat atrial fibrillation using a variety of clinical techniques in the EP lab. Through this new catheter, our main objective is to be able to give the electrophysiologist a single tool in which they are able to reduce the procedure times from where they are today down to the one- to two-hour range. The third area of our focus is on using our catheter-based technology to develop a minimally invasive probe for treatment of atrial fibrillation in the operating room. We have received 510k clearance for our initial product, called the Breva, for the minimally invasive surgical market. You may ask why an EP company wants to develop a product for surgeons, and there are actually several reasons. Number one, we can utilize our substantial experience in developing disposable products, but more importantly, disposable products that can be manipulated from outside the body. This allows the surgeon to make a single puncture through the chest wall for catheter delivery and use the catheter to treat AF in a very minimally invasive manner. We believe there is going to be a growth in minimally invasive surgical treatments. Today cardiac surgeons treat atrial fibrillation predominantly in patients who have concomitant valve disease or bypass surgery where surgery is indicated. However, opening the chest of a patient with AF only is really not something most patients will desire. If we evaluate the growth trend in cardiac surgery for arrhythmias, most of it is going to occur based on estimates in the minimally invasive area. We feel that with our expansion into the minimally invasive approach to atrial fibrillation surgery, we can now offer the patient a solution that can be done in the EP lab with a puncture in the groin or a procedure in the operating room with a small puncture in the chest wall. Then the patient can ultimately decide which technique they would like to have used. We believe we have a competitive advantage in that area because we have been developing catheters that then can be adopted to the minimally invasive approach for cardiac surgery. For more information about CryoCor or about the clinical trial, please visit their website: www.cryocor.com