After a period of about nine months apparently on hold, the clinical trial of the AbioCor replacement heart made by Abiomed (Danvers, Massachusetts) picked up speed last month, with the company reporting a second implant in January, the two most recent at Jewish Hospital in Louisville, Kentucky. The earlier implant took place on Jan. 7, the latest on Jan. 22, both performed by heart surgeons Laman Gray and Rob Dowling, who have carried out five of the total of nine procedures.
The two patients briefly joined Tom Christerson, who was implanted with the heart in November 2001 and had been supported by it for about 17 months prior to his death Feb. 7 as the result of component wear that affected the fluid power of the AbioCor's engine.
The January recipients of the AbioCor heart were described by the hospital as being in "critical but stable" condition. No additional details were given out, not even whether they are male or female, continuing the policy of withholding specifics to maintain focus on care of the patients and protect the privacy of their families.
Ed Berger, PhD, vice president of strategic policy and planning at Abiomed, said there have been "no formal changes in patient criteria" to explain the rapid occurrence of two new implants. But he said that a possible reason for trial speed-up may be the company's "very intensive outreach to cardiology practices in a fairly broad geographical area surrounding Louisville during December." He said that over a two-week period last month "a team of high-level managers from the AbioCor clinical trial went out and made visits, presentations and sat and participated in some transplant conferences. We got to know some of the cardiologists and really had a chance to brief them in a very direct kind of way." The goal of that effort, he said, "was to make sure that the cardiologists caring for the patients who might be candidates for the AbioCor really understood the status of the trial, the nature of the experience, the kinds of patients we're looking for."
Berger said that after the outreach effort there had been a considerable increase in referrals to the trial. Rather surprisingly, he said that Abiomed had found some cardiologists that knew of the trial only from their local press sources and even a small group a "subset," he said who had thought the trial had been canceled. "One of the issues has been that this sort of clinical trial really is greatly affected by momentum," said Berger. "The trial was never officially paused, but there was a purposeful hiatus," providing time to make changes in portions of the mechanical heart controlling what he termed "inflows."
He said it had taken the company a while "to understand the way in which that slowdown had caused all the momentum in the trial to disappear." Overall, he said that probably "several dozen" referring physicians had been, in a sense, re-educated to the trial and that the company now remains on pace and optimistic about completing the 15-patient trial by mid-year. He added: "It's not a guarantee, but the fact that we implanted two [patients] in January gives us more reason to be optimistic" about the trial's timeline.
The death of Christerson which was attributed for the first time in the trail specifically to a device breakdown will not hamper trial completion, said Dr. David Lederman, company CEO. Lederman said Abiomed was "saddened" by the death but that the AbioCor had provided Christerson several added months of life at home, calling that "an historic achievement." He said that the "gradual wear" of a component had come as no surprise. "We have been testing systems in our laboratories that incorporate improvements that we believe will substantially increase the durability and reliability of this and other components" but that the trial will continue with the AbioCor as "currently configured."
Impressive 5-year TMR results presented
When introduced to the U.S. market in the summer of 1998, many industry observers expected that transmyocardial revascularization (TMR) would be adopted rapidly by the cardiac surgery community. For a variety of reasons, the acceptance of TMR has been sluggish, and the growth of the two domestic TMR companies, PLC Systems (Franklin, Massachusetts) and CardioGenesis (Foothill Ranch, California), has been very disappointing.
Cardiac surgeons may be one of the most, if not the most conservative medical specialists, requiring that the products and procedures they employ have demonstrable long-term durability, safety and efficacy. Initially, surgeons were reticent to use TMR widely, lacking confidence in its long-term efficacy. However, this concern began to be allayed in late 2000, when a paper presented at the American Heart Association's (Dallas, Texas) annual scientific sessions indicated that the procedure provided patients angina relief for five years. That study employed the PLC carbon dioxide TMR laser.
More recently, the industry's market leader, CardioGenesis, with an estimated 75% sector share, reported that patients treated with its proprietary holmium YAG had also provided sustained, five year-plus, angina improvement. Those results were initially presented at the Angiogenic Gene Therapy Global Workshop, which was held in New York in mid-December and then released by the company last month.
At this year's annual meeting of the Society of Thoracic Surgeons (Chicago, Illinois) in San Diego, California, late last month, Keith Allen, MD, a cardiovascular surgeon at St. Vincent's Hospital (Indianapolis, Indiana), presented this data to a standing-room-only crowd at the CardioGenesis booth. Allen's hospital was one of the two centers involved in this trial, the other being Jewish Hospital (Louisville, Kentucky). These two hospitals also were part of the pivotal Angina Treatment-Lasers And Normal Therapies In Comparison (ATLANTIC) clinical trial that supported the FDA's approval of CardioGenesis' TMR application in early 1999.
Allen said that there have been five separate prospective, randomized clinical trials comparing TMR to best medical management. While each of these trials has amply demonstrated that TMR is superior, it is important to note the most impressive results have been attained in those patients suffering the most severe and debilitating angina pain. In this five-year study, these so-called Class 4 patients (as measured by the Canadian Cardiovascular Society quality-of-life angina score) enjoyed the most significant benefits compared to patients treated with lesser angina, with 96% of those surviving experiencing a two-class drop in their angina score. Commenting on these five studies, Allen said that "it is very clear that patient selection is a critical factor in providing maximum patient benefit," and that Class 4 patients experience the most "dramatic benefit."
He also said that the ATLANTIC trial not only showed excellent quality of life or subjective benefits but also provided very strong objective evidence of angina relief, as measured by a statistically large improvement in exercise treadmill endurance time.
Noting that coronary artery disease (CAD) is a "malignant, long-term problem," Allen said it was not realistic to expect CAD patients who receive TMR therapy to live longer but that their enhanced quality of life, as measured by a lower angina score, was very meaningful. In addition, their number of costly hospital visits has been reduced. He said that "TMR does provide sustained angina relief compared to best medical management, and I believe it is an important tool in the surgeon's armamentaria of treatment options."
In a conference call with investors following release of its 4Q02 results, Edwards LifeSciences (Irvine, California) disclosed that its TMR business, involving exclusive distribution of PLC Systems' products, enjoyed strong results, registering about $3.5 million in revenue. The company predicted robust TMR results for fiscal 2003, with a range of revenue estimated at $12 million to $16 million.
Edwards entered the TMR market in January 2001, when it signed a marketing alliance with PLC that gave it exclusive distribution of that company's second-generation TMR technology. Almost exactly a year later, Edwards exercised its option to assume full sales and marketing responsibility in the U.S. for PLC's laser system and associated disposables.
Meanwhile, in mid-January, CardioGenesis said that it expected to report 4Q02 revenue in the range of $3.5 million to $3.7 million, a more than 25% increase from 4Q01. It attributed these results to strong handpiece and laser sales. Final results for this period have not yet been released.
Given these two recent announcements, it appears safe to say (paraphrasing Mark Twain) that reports of TMR's death appear greatly exaggerated.
Surgical AFib treatment gains
In other Society of Thoracic Surgeons-related matters, interest in the surgical treatment of atrial fibrillation (AFib) appears to be gaining momentum. With the aging of the population, AFib is a growing clinical problem in search of innovative, less-invasive and efficacious solutions. Cardiac surgeons, who perform coronary artery bypass or valve surgery on patients who often present with chronic AFib, are well positioned to participate in providing a surgical solution.
The early device market leader is venture capital-backed AtriCure (Cincinnati, Ohio), which introduced the AtriCure TransMurTech Bipolar System in the U.S. in mid-2002. Its technology allows the surgeon to perform a Maze-like adjunctive open surgical procedure in 15 minutes or less. Atricure believes that this domestic market opportunity could be 75,000 to 100,000 procedures annually. The company also is developing a stand-alone minimally invasive procedure, which addresses a much larger market opportunity.
AtriCure's device uses bipolar radio-frequency energy to create transmural, linear lesions that easily and rapidly can electrically isolate the tissue, compared to the difficult, time-consuming scalpel and suture methods in the Maze procedure. The company says that its technology is the only one that demonstrates when a transmural lesion has been formed, measuring the conductance of soft tissue.
Some other companies involved in this emerging market include Edwards LifeSciences, which recently acquired CardioFocus's (Norton, Massachusetts) surgical photonic ablation laser technology; Cardima (Fremont, California), which recently received 510(k) approval for its Surgical Ablation System providing an alternative to the Maze procerdure; Medtronic (Minneapolis, Minnesota), which introduced its Cardioblate radiofrequency ablation system about a year ago; the EP Technologies division of Boston Scientific (Natick, Massachusetts), which is marketing the Cobra RF electrosurgical system; and privately owned Estech (Danville, California).