According to the American Heart Association, there are more than 1.5 million cases of myocardial infarctions in the US each year. In a majority of these patients, their heart tissue undergoes significant damage post infarction. TherOx, a company based in Irvine, CA, has been developing a novel therapy to improve care for patients who have had heart attacks. Medgadget previously reported on TherOx’s first generation device to deliver hyperbaric levels of oxygen to the heart to restore oxygenation of tissue affected by acute myocardial infarction. The company has now developed a second generation product and Medgadget spoke with Kevin Larkin, President and CEO of TherOx, to learn more about what the company has been up to lately and get some details about the new device.
Gaurav Krishnamurthy, Medgadget: Could you give me a background about TherOx and how it was founded?
Kevin Larkin: TherOx has been a Delaware Corporation since 1995 and is venture capital financed. A Detroit-area interventional cardiologist observed that treating heart attack (AMI) and stroke patients in hyperbaric chambers improved their recovery. Since AMI is the result of a blocked or obstructed coronary artery that decreases oxygen delivery to heart tissue, it is clinically intuitive that delivering significantly greater oxygen to ischemic tissues via a hyperbaric chamber recovers more tissue that would otherwise die or infarct. As one might imagine, treating AMI patients who require frequent patient care interaction in a pressurized chamber is completely impractical. The interest in developing a better, targeted, and catheter-delivered hyperbaric equivalent for more complete tissue recovery and smaller infarcts served as the impetus to form TherOx. Our company was founded to develop a hyperbaric equivalent by dissolving a large volume of oxygen in a smaller volume of saline, creating a supersaturated oxygen solution that could then be infused into the previously obstructed but now opened coronary artery to restore normal oxygen to the ischemic tissue.
Creating a supersaturated solution that doesn’t bubble or act like a carbonated beverage is quite a challenge. TherOx does this extremely well and has this technology well-protected with patents.
Medgadget: What is Super Saturated Oxygen (SSO2) treatment and how does it help patients who have had MI?
Kevin Larkin: A heart attack is typically caused when a blood vessel carrying oxygen to the heart is blocked or obstructed. If blood flow is not quickly restored, irreversible damage to the heart muscle, or infarction, will occur. SSO2 Therapy was developed to reduce infarct size by significantly boosting oxygen delivery to the heart muscle immediately after the coronary artery has been opened by percutaneous coronary intervention (PCI – angioplasty and stenting). The TherOx system creates SSO2 Therapy by mixing highly oxygenated saline with some of the patient’s blood and delivers it through a catheter directly to the targeted ischemic (damaged) area of the heart.
AMI is a leading cause of death. Smaller infarcts always produce better patient outcomes than larger ones. Even so, among survivors, AMI is a leading cause of complications and among large anterior MI survivors it is the leading cause of heart failure.
Medgadget: How is the second generation product better than the previous TherOx version?
Kevin Larkin: This second generation system being studied includes the additional benefits of shortening the treatment time from 90 to 60 minutes and broadening the treatment area from one branch of the heart to the entire left coronary system so that no ischemic area goes untreated.
The first generation therapy delivery used a separate small infusion catheter advanced inside a guide catheter. The guide catheter was placed in the left coronary opening or ostium. The infusion catheter was then advanced through the guide and into one branch of the left coronary artery (the LAD branch) and positioned with the tip near the freshly placed stent as shown in the illustration. While this delivery reduced infarct size compared to PCI, it treated ischemia only in the region of the heart fed by the LAD branch. The first generation treatment time was 90 minutes.
The second generation system builds on the success of the first generation and uses an angiographic type catheter positioned in the left coronary ostium which infuses virtually the whole left ventricle not just the LAD region. This enables treating a greater area of ischemia than before for more complete coverage. This catheter and position also enable increasing the infusion flow rate which enables shortening the treatment time to 60 minutes. These changes improve resolution of ischemia virtually anywhere in the left ventricle.
Medgadget: Has the previous version proven itself in trials?
Kevin Larkin: Yes, the first generation system to deliver SSO2 Therapy was successful in meeting the safety and effectiveness endpoints in the AMIHOT II controlled, randomized, pivotal trial. Statistical results from the AMIHOT II trial of SSO2 Therapy, together with PCI and stenting, demonstrated a relative reduction of 26% in infarct size compared to the standard of care, PCI alone. In addition, the finding of device effectiveness was supported by analyses showing 53% greater likelihood of having a small (less than 5%) infarct among SSO2 Therapy patients. The results were published in Circulation: Cardiovascular Interventions (link).
Additionally, Leiden University in the Netherlands conducted single center further analysis due to having advanced software enabling measurement of ventricular volumes at 30 days among their SSO2 treated patients and those receiving the PCI standard of care. Ventricular dilation or enlargement at 30 days is an indicator of being on the heart failure path. Among Leiden’s SSO2 treated patients there was no ventricular enlargement. PCI treated patients showed 13% enlargement. The results of this study are published in the American Journal of Cardiology.
Medgadget: Are there any competitors providing similar SSO2 therapies?
Kevin Larkin: During the last five-to-eight years, over a dozen attempts have been made with drugs and devices to reduce infarct size. These have included cooling catheters, thrombectomy, thrombolysis, and cardio-protective drugs. None of these has been effective since they don’t treat and resolve the underlying ischemic condition like SSO2 does. These numerous attempts reinforce the clinical need and recognition that more can be done to improve outcomes for AMI patients.
No potential competitor is pursuing the same approach as TherOx is with SSO2 therapy. It’s technically difficult to do and now protected by over 70 US and 100 OUS patents. However, we are starting to see some broader feasibility activity in the AMI market due to its size and unmet clinical need.
Medgadget: When will this second gen product be available in market?
Kevin Larkin: The second generation system is CE Marked and can be sold in European countries. In the US, TherOx just completed the pilot phase of an IDE study intended to provide evidence that the new therapy is easier to administer, more effective and has a better safety profile than the first generation. In a small patient population it accomplished all three. With adequate financial resources to initiate the pivotal phase, it will take us two years to enroll patients in the trial and an additional 6-12 months for PMA approval.
Product page: THEROX DownStream System…