Three of the major players in the cardiovascular device sector – Medtronic (Minneapolis, Minnesota), Guidant (Indianapolis, Indiana) and St. Jude Medical (SJM; St. Paul, Minnesota) – found themselves in very much the same boat in recent weeks, all experiencing problems with their implantable products.
St. Jude's problem was clearly the most serious, since it is has been forced to recall an entire product line. In late January, it said it was voluntarily recalling all of its heart valve replacement and repair products using its Silzone coating on the sewing cuff fabric and that it will no longer distribute any products with the Silzone coating. In mid-February, Medtronic and Guidant issued warnings to physicians about specific products. Medtronic issued physician notifications concerning a small number of its Gem II defibrillators that might work erratically; and Guidant said it was notifying physicians of a potential part failure in its Prizm implantable cardioverter defibrillator (ICD).
Following announcement of the Medtronic and Guidant problems, St. Jude Medical was back in the barrel with another defect problem. The company began sending out notifications the nearly 900 of its Affinity pacemakers potentially could fail because of a defect. The three Affinity models – 5120, 5230 and 5330 – were launched recently by SJM's pacemaker division in Sylmar, California. In a letter to cardiologists, St. Jude said the pacemakers could show "intermittent loss of output" because of a failure in the connection between a resistor and the rest of the device's circuitry.
The company estimated that up to 90 of the defective models might fail over the next five years. It did not launch a total recall of the product. Rather, St. Jude said it would pay up to $800 of nonreimbursed cost for explant. The need for explant, the company said, should be a clinical judgment made by physicians.
The problems with the Affinity pacemakers came to light about two weeks after St. Jude was forced to withdraw one-quarter of its mechanical heart valve product line because of the Silzone coating problems. That action could result in a one-time charge to the company of up to $20 million, and the Affinity problem is likely to increase that figure substantially. SJM launched the earlier recall and replacement effort following an analysis of clinical trial results involving the Silzone-coated mechanical heart valves. That data indicated "an unacceptable level of product explants as a result of a specific postoperative complication known as paravalvular leak," St. Jude said in a statement.
Titled AVERT – for Artificial Valve Endocarditis Reduction Trial – the trial compared the incidents of endocarditis, a post-operative infection that can be fatal, in valves with and without Silzone, as well as looking at other complications associated with valve replacement surgery. The problem does not involve the valve mechanism or the design and manufacture of the product, but "appears to be associated with the Silzone-coated sewing cuff fabric," the company said in a statement. Eight explants for paravalvular leak were reported, out of a total of 398 patients enrolled in the Silzone trial arm, compared to one leak reported in the 394 patient non-Silzone arm.
The recall is substantial, since it relates to about 25% of SJM valves, the Silzone technology intended to reduce the occurrence of endocarditis in valve procedures. About 36,000 of the valves have been implanted worldwide. The is likely to slow near-term earnings since the product was expected to enhance SJM's share of the valve sector. But upcoming product rollouts are expected to keep the company's long-term prospects healthy, according to analysts.
Steven Healy, president of St. Jude's Heart Valve Division, predicted that "only a very small number" of those who had received the valves would require valve explant or any other intervention, "other than the normal patient monitoring that is standard for individuals with prosthetic heart valves."
On Feb. 11, Medtronic began notifying doctors concerning the problem with its Gem II defibrillators, saying that about 50 of 1,100 units released in the U.S. since last May might work erratically. Medtronic spokeswoman Diana Campau said the company is advising doctors that patients with the devices should activate its Patient Alert System, instrumentation that warns the patient concerning any problems with the unit.
Three days later, Guidant issued its own warning letter to physicians, alerting them to a potential part failure in its Prizm implantable cardioverter defibrillator. Guidant said it estimated the malfunction might occur in fewer than two out of 364 devices produced between Aug. 13 and Sept. 7, 1999. Guidant was alerted to the problem by a physician who reported that the device was pacing too fast in a procedure that was scheduled to be performed the previous week. That procedure was canceled and the patient remains hospitalized, the company said.
"Based on our investigation of that observation, we identified a random component failure that had the potential to occur in a small subset of devices," said Guidant spokesman Rob Allen. The company said physicians can perform a non-invasive test on patients who have had the device implanted to ensure that it is functioning properly.
In announcing the problems, both companies said that they had not received any reports of injuries.
The product glitches did not disturb the shareholders of either company very much. Medtronic's stock price dipped slightly when rumors of the physician warning began spreading, and Guidant's stock actually rose slightly the day it reported its alert.
300 mitral valve surgeries with AESOP
At the 36th annual meeting of the Society of Thoracic Surgeons in Fort Lauderdale, Florida, in late January, Computer Motion (Goleta, California) reported completion of three clinical series totaling more than 300 minimally invasive mitral heart valve surgeries with the assistance of the company's AESOP 3000 with voice control robotic system. More than 200 of the surgeries have been performed with AESOP by Friedrich Mohr, MD, PhD, chief of cardiac surgery and his team at the University of Leipzig (Leipzig, Germany). Mohr said that with the system, the team produced "safe, reliable and repeatable operative results with less patient pain, trauma and recovery time." W. Randolph Chitwood, MD, chairman of the department of surgery and chief of cardiothoracic surgery at East Carolina University School of Medicine (Greenville, North Carolina), has performed more than 60 procedures with AESOP. He said the system provides "direct control over the operative view," highly predictable endoscope movements, and totally motionless imaging, allowing concentration "on the precise surgical maneuvers required to perform these delicate procedures."
CryoLife breaks ground for addition
CryoLife (Kennesaw, Georgia), a developer of implantable human tissues for use in cardiovascular, vascular and orthopedic surgeries, stentless heart valves, and surgical adhesives, has broken ground for an addition to its headquarters campus. Consisting of a two-story, 100,000-square-foot medical device manufacturing laboratory facility, the addition will include manufacturing facilities for SynerGraft heart valves and BioGlue surgical adhesive, as well as physician training laboratories, a 150-seat conference area, and additional corporate office space.
Steven Anderson, president and CEO, said that the need for the expansion was driven by the growing demand for the company's BioGlue and SynerGraft products. "This additional space will allow us to incorporate the manufacturing operations that are currently off-site into one location and to accommodate future growth," he said. It also will include a physician training facility. When completed by mid-2001, the CryoLife corporate campus will comprise three state-of-the-art buildings with 205,000-square feet on 15 acres, "giving us the space we need for many years to come," Anderson said.
CryoLife also reported the opening of the European headquarters for which it had announced plans in August 1999. The new headquarters of CryoLife Europa Ltd. is a 5,600-square-foot building located in Fareham, Hampshire, U.K., and includes warehousing, a conference room and training laboratory for surgeons and distributors. It is under the direction of Robert Hanley, PhD, president of CryoLife Europa.
News of new funding
CardioTech International (Woburn, Massachusetts) has received a Small Business Innovation Research grant of $99,937 from the National Heart, Lung and Blood Institute (Bethesda, Maryland) to evaluate the use of brachytherapy techniques to eliminate anastomotic hyperplasia in small bore vascular grafts. The grant was awarded to CardioTech in collaboration with Implant Sciences (Wakefield, Massachusetts), and Stanford University School of Medicine. CardioTech synthesizes, designs and manufactures medical-grade polyurethanes used in vascular graft technology and other implantable devices.
Corvas International (San Diego, California) has received nearly $9 million from the exercise of warrants held by International Biotechnology Trust plc and two Weiss Peck & Greer funds. The warrants were issued in connection with a private placement in February 1996 to institutional investors who at that time purchased 3 million units, each consisting of one share of common stock and one warrant to purchase an additional share of common stock. Corvas is developing therapeutic agents for cardiovascular, stroke, cancer, and other applications.
Hemosol (Toronto, Ontario, Canada) reported receiving more than C$4.5 million from the exercise of just over 1.2 million common share purchase warrants. Combined with a new C$10 million credit facility, the funds will be used to support release of the results of its Phase III clinical study, which it termed "nearing completion in the U.K. and Canada." Hemosol is the developer of Hemolink, a blood substitute.
Vasogen (Toronto, Ontario, Canada) said it has received commitments, primarily from senior U.S. institutional investors, to purchase directly 1.6 million special warrants at C$9 per special warrant, raising approximately C$14.2 million after expenses. Proceeds will be used to advance the development of Vasogen's proprietary immune modulation therapies in cardiovascular, autoimmune and related inflammatory diseases.