CD&Ds

Doing business in med-tech is at once both complicated and simple. As an example of the latter, a nod from the FDA is all a company needs to make some serious headway in the market.

Take Cardica (Redwood City, California) for example. Shares for the California-based company shot up more than 35% at $10.70 a share on the same mid-September day that it issued a press release noting 510(k) clearance to market its PAS-Port Proximal Anastomosis System for use in cardiac bypass surgery in the U.S.

Until now, the system was limited to sales in Europe and Japan, but FDA approval opens up a floodgate of patients who're looking for a safer, less-intrusive means of cardiac bypass surgery.

"With the introduction of the PAS-Port system in the U.S., cardiothoracic surgeons are now provided with a complete package of reliable, automated revascularization systems for use in CABG procedures," President/CEO Bernard Hausen, MD, PhD, said during a conference call.

He added, "We believe that by replacing hand-sewn sutures, our automated proximal and distal anastomoses systems can help cardiovascular surgeons perform consistent, reliable anastomoses with even the smallest of vessels, giving surgeons greater ability to use minimally invasive techniques for cardiac surgery."

Hausen said Cardica plans to launch PAS-Port in the U.S. in the next several weeks with "a systematic and deliberate roll-out to surgeons and [we] look forward to training 50 to 60 surgeons per quarter, as we previously have discussed."

The device creates a secure connection between the body's main artery and vein grafts. It differs from the current method of connecting a bypass graft vessel to the aorta in CABG surgery, which often requires that the aorta be clamped and utilizes time-consuming, hand-sewn sutures. When the clamp is released, tiny blood clots or particles from the aortic wall can be released, which can travel to the brain and cause stroke and other neurologic complications.

The company said the PAS-Port system allows a surgeon to complete an automated proximal anastomosis without the need to clamp and manipulate the aorta. Eliminating the clamp may greatly reduce the risk of particle release and ensuing neurocognitive events, it said.

Put another way, this means an attachment to a vessel of 3 mm or more in diameter, using a clamping or "coupling" approach, compared to connection to a vessel of just 1 mm in diameter, using the delicate stapling method.

"PAS-Port leaves no metal or aluminum in the graft and it reduces occurrences of restenosis," Hausen said, calling the device a "major milestone". The system's design allows surgeons to load the bypass graft into the system and rapidly complete the anastomosis, typically in about a minute.

This reduces the time required for the anastomosis while providing a consistent, reliable connection. The bypass graft is loaded into the system without damaging endothelial cells, while maximizing the orifice, which is especially important with a small graft. No metal is within the lumen of the graft vessel.

According to results from the pivotal clinical trial of the PAS-Port system, anastomosis surgical time is significantly reduced compared with hand-sewn anastomoses. Patient outcomes may be improved due to shortening of surgery times and hospital stays and reducing complications associated with aortic clamping.

Cardica conducted a 220-patient, prospective, pivotal, randomized trial of PAS-Port at 12 sites in the U.S. and Europe. The trial compared venous bypass graft vessel connections to the aorta made using the PAS-Port system versus those made using conventional hand-sewn sutures. Results showed that the study met its primary endpoint of non-inferiority to hand-sewn anastomoses, as well as all other primary and secondary endpoints.

As of June 30, more than 8,800 PAS-Port systems had been sold worldwide, with the vast majority of units deployed in Japan. According to Cardica's Japanese distributor, the PAS-Port system is used in more than 20% of all proximal anastomoses performed using a vein bypass graft during CABG surgeries in Japan.

Cardica expects to have 50 to 60 surgeons trained to use the device per quarter.

Elsewhere in the product pipeline:

•The National Institutes of Health (NIH) has informed CHF Solutions (Brooklyn Park, Minnesota) that the CARRESS-HF trial has begun enrolling patients. Sponsored by NIH's National Heart, Lung, and Blood Institute and chosen out of 16 national submissions for studies in heart failure, this study will compare CHF Solutions' Aquapheresis therapy with standard medical drug therapy in patients hospitalized with acute decompensated heart failure and cardiorenal syndrome. Fluid overload can be caused by problems with the heart, kidneys, liver and lungs, and is frequently experienced after surgical operations, trauma, and burns. The leading cause of fluid overload is congestive heart failure (CHF), sometimes referred as just heart failure. Heart failure is a condition that affects about 5 million Americans and is responsible for over 3.1 million primary and secondary hospitalizations annually. CHF Solutions' Aquapheresis therapy is a mechanical method to safely and effectively remove the excess salt and water in patients with fluid overload.

•Digirad (Poway, California) reported the initial clinical trial of a new imaging system, Cardius X-ACT, using new technology to correct attenuation, or image distortion, an inherent issue in cardiac SPECT imaging. Cardiac SPECT (single photon emission computed tomography) also called myocardial perfusion imaging is a non-invasive test to assess the heart's structure and function. Small amounts of radioactive substances are injected into a patient's vein, and special cameras produce images of the heart. These SPECT images are used to identify blockages in coronary arteries, determine whether a patient has had a heart attack, evaluate risk of a heart attack, and assess condition after bypass surgery or angioplasty.

•Edwards Lifesciences (Irvine, California) has presented new data on the Edwards Sapien transcatheter heart valve with the Ascendra transapical delivery system. The SOURCE trial is designed to evaluate commercial use of the Sapien valve with a prescribed training and proctoring program. It is a registry of procedural and short-term clinical outcomes. The current data reflect 309 cases at hospitals in 12 European countries. Survival at 30 days was 88%.

•iCardiac Technologies (Rochester, New York) reported the completion of what it said is the industry's largest validation study for an automated ECG analysis technology. The company said the results of the study make iCardiac's technology the first to comply with the FDA E14 industry guidance. In the validation study, iCardiac's automated QT method has demonstrated results equivalent to manual measurements performed independently by U.S. board-certified cardiologists. The automated QT method was shown to reliably detect the effect of the drug moxifloxacin. Moxifloxacin is used as a positive control in cardiac safety studies and is included in the FDA's E14 industry guidance. QT analysis is part of iCardiac's software platform, COMPAS 3.0. The platform provides comprehensive analysis of cardiac repolarization signals and contains several advanced arrhythmia biomarkers, as well as ECG signal processing tools.

•Inverness Medical Physician Diagnostics Group (San Jose, California), a division of Inverness Medical Innovations (Waltham, Massachusetts) reported the launch of the INRatio2 PT/INR monitoring system, a portable device that measures blood-clotting time, also known as prothrombin time, using one drop of blood from a patient's finger. The INRatio2 is used by healthcare professionals and their patients in the management of warfarin, a blood-thinning drug, to monitor the effectiveness of the drug and warn of potential blood clots and other bleeding risks. The INRatio2 PT/INR has been cleared by the FDA for warfarin patients to test themselves at home, offering patients quick access to their PT/INR results. The test results are then transmitted to their treating physician by telephone or internet.

•Medtronic's (Minneapolis) Talent thoracic stent graft is safe and effective compared to open surgery, according to research published by the Society for Vascular Surgery (SVS; Chicago) in the September issue of the Journal of Vascular Surgery. The FDA approved the device in June for certain aneurysms of the descending thoracic aorta, but has been available outside the U.S. since the late 1990s. "The Talent thoracic device, first of all, carries a legacy of experience. It is the most implanted thoracic device in the world, it has been available outside the U.S. since 1997," Simona Zannetti, MD, senior director of clinical affairs for Medtronic Endovascular Innovations, told CD&D. The Talent system is designed to provide a minimally-invasive treatment alternative to open surgery for patients with life-threatening aneurysms in the upper portion of the aorta, the body's largest artery. Thoracic aneurysms affect about 30,000 people a year in the U.S., causing thousands of deaths. The procedure involves threading the stent graft through a small opening in the femoral artery of the leg. The graft is advanced under fluoroscopic guidance to the site of the thoracic aortic aneurysm, where it is then positioned and deployed from the delivery system. Once deployed, the stent graft expands to fit snugly within the diameter of the aorta, providing a new path for the blood flow.

•The Sorin Group (Arvada, Colorado) reported the first successful uses in the U.S. of its newest pediatric devices for cardiovascular surgery. The Dideco KIDS D101 pediatric oxygenator and the Dideco KIDS D131 pediatric arterial filter have now been successfully used by Children's Medical Center Dallas during dozens of cardiac surgery procedures for pediatrics. The Dideco KIDS D101 oxygenator is designed to minimize hemodilution and reduce foreign surface area exposure; the D101 is specially proportioned to the pediatric patient. Its low surface area results in a more balanced oxygen and carbon dioxide transfer, and the innovative D101 design has the low priming volume of 87 mls while addressing the cardiopulmonary bypass needs of pediatric patients. The Sorin Group makes cardiac surgery devices.

•St. Jude Medical (St. Paul, Minnesota) has developed an implantable cardiac monitor (ICM) the size of a computer thumb drive designed to provide more accurate sensing of abnormal heart rhythm signals in difficult-to-diagnose cases in which standard monitoring tests are not enough. FDA has cleared the SJM Confirm ICM, which it says will help physicians diagnose and document difficult-to-detect rhythm disorders in patients who may suffer from unexplained symptoms, including fainting, palpitations and shortness of breath. At 6.5 cc, the Confirm is the smallest ICM on the market, according to the company. The device is implanted just under the skin in the upper chest region during an outpatient procedure under local anesthesia. "It is the smallest cardiac monitor available, it provides real time data and some devices that are out there do not do that," Kathleen Janasz, a St. Jude spokeswoman, told CD&D. Janasz also said it was important that the Confirm ICM is approved for syncope (or, fainting), which is "one of the most difficult diagnoses to make." According to St. Jude, syncope is responsible for about 3% of all emergency room visits and up to 6% of all hospitalizations.

•Patients with heart failure who no longer get symptom relief from medications may have a new treatment option on the horizon with FDA's conditional approval last month of an investigational device exemption (IDE) to Sunshine Heart (Sydney, Australia) to begin its first U.S. clinical trial for the C-Pulse, an implantable aortic cuff heart assist device. "Almost 1.4 million patients have moderate heart failure," Sunshine CEO Donald Rohrbaugh told CD&D. "Thirty percent have an electrical disorder and pacemakers are addressing this problem. But that leaves 70% with a large unmet clinical need. They have a progressive condition and they often end up with end-stage heart failure." Sunshine's cuff, which functions like a blood pressure cuff, wraps around the aorta and a balloon inflates to displace blood in the aorta. It's being positioned as a Class III heart failure therapy that offers an intervention bridging the clinical gap between heart failure pacemakers and end-stage therapies. Implantation is performed via a simple surgery on a beating heart, without the need for heart-lung bypass or any incisions to the heart or great vessels. Enrollment is expected to begin at six U.S. medical institutions by the end of 2008.

•Volcano (San Diego) reported the use of its VH IVUS in GlaxoSmithKline's IBIS-2 trial. In the study, Volcano's VH IVUS technology demonstrated and quantified compositional changes in atherosclerotic plaque that occurred over time. In IBIS-2, VH IVUS showed compositional changes in the placebo group that suggest continued progression of necrotic core despite standard of care therapy. Use of the novel Lp-PLA2 inhibitor, darapladib, plus standard-of-care therapy prevented this progression. VH IVUS is a catheter-based technology that creates colorized tissue maps of plaque composition in real time. The technology uses spectral analysis techniques to allow simplified interpretation of ultrasound images and provide detailed information on the composition of each patient's atherosclerotic plaques. The color VH images show four plaque component types: necrotic core, dense calcium, fibrous and fibro-fatty.