Guidant (Indianapolis, Indiana) said in mid-June that it will discontinue its Ancure Endograft System product line for the treatment of abdominal aortic aneurysms (AAA). The decision to discontinue the product line came about a week after the company's EndoVascular Technologies (EVT; Menlo Park, California) subsidiary said it planned to settle government charges that it made fraudulent statements to regulators concerning the device, pleading guilty to 10 felony counts and making a settlement of more than $92 million. That announcement was followed by a small avalanche of shareholder suits, but the company promised that, overall, these and potential civil litigation will have no material impact on operations.

The 10 counts of felony charges include nine related to selling a misbranded product and one related to making false statements to the FDA. The company intentionally misled an FDA inspector, giving him 55 complaints vs. several hundred that the company was aware of. Over an 18-month period from September 1999, when the FDA approved the device, to March 2001 when the company voluntarily removed the product from market Guidant filed 172 medical device reports (MDRs) but has said that an additional 2,628 MDRs occurred out of 7,632 Ancure devices sold.

Guidant acquired EVT in 1997, and the AAA business represented less than 1% of total sales in fiscal 2002, or about $63 million of Guidant's $3.2 billion total for that year. The company stressed during a conference call and in its press statements that patients implanted with the Ancure are not at risk as a result of its decision to discontine the product line. "If you are a patient with an Ancure implant, I want to assure you and reassure you that your implant is safe," said Ronald Dollens, Guidant president and CEO. "Guidant management acknowledges and regrets what happened at EVT. We are committed to ensuring that our company and all of our businesses have the best compliance system in the industry." He said that people who should have known better acted improperly and displayed poor judgment, and added: "Once that improper conduct was recognized, Guidant promptly overhauled the business."

The company said it would continue to ship product and provide support to implanting Ancure physicians and their patients through Oct. 1, 2004. Beyond that date, Guidant will continue to support implanted patients and physicians for long-term follow-up and device tracking needs. But other than those activities, EVT will cease operations. "We are grateful to the many physicians who relied on the Ancure Endograft System for treating patients with this serious condition," Beverly Huss, president of Guidant's Endovascular Solutions unit, said in a statement. "We understand that the discontinuation of the product will involve a time of transition, which we pledge to make as smooth as possible." The company also said that most affected employees will be offered other positions within Guidant and that carotid, biliary, neurovascular and peripheral product development initiatives will not be impacted by the reorganization.

Dollens termed as "unaccepetable" the series of events that occurred at EVT leading up to the withdrawal of Ancure in March 2001. "EVT had MDR information and intentionally failed to report it," he said. "This is not the way we conduct our business." Dollens noted that the new management team put in place at the beginning of 2001 and the current employees "have undergone extensive efforts to put the house in order." He said those efforts culminated in the reintroduction of the device in August 2001.

Ralph Hall, general counsel for Guidant, noted that EVT is the party charged in this matter, not Guidant, a distinction that the company hopes it can convince a jury to accept. However, he acknowledged that 14 civil suits naming Guidant had been filed to that point and said he expected more in the future. However, he said he believes the scope of the matter is "limited," with only 5% of the just under 7,700 persons who have received Ancure implants regarded as patients who had faced any "serious adverse consequences." These consequences, he added, "were consistent with the clinical results from the initial product approval and re-approval of the device."

The company said that by the end of June, an agreement should be reached with the Department of Health and Human Services (HHS) regarding corporate reporting requirements still another concern since HHS could exclude the company from such government programs as Medicare. "I think the great majority, if not all, of what the government needs to see in order to be reassured is in place," Graf said.

Northfield wins SPA from CBER

Blood substitute firm Northfield Laboratories (Evansville, Illinois) last month reported a new agreement with the FDA's Center for Biologics Evaluation and Research (CBER), which the company said will have at least two important benefits: It could provide a clearer path to product approval with successful completion of a new Phase III trial, and it should provide a positive story to tell financial institutions. Northfield said that it has reached agreement with CBER on a Special Protocol Assessment (SPA) for its pivotal Phase III prehospital trial for PolyHeme, the company's oxygen-carrying product. This follows approval of the trial granted by the agency in March.

Steven Gould, MD, chairman and CEO of Northfield, told The BBI Newsletter that the importance of the SPA is to create contractual expectations with CBER concerning the specific protocol and outcomes of the trial, thus producing a much greater sense of exactness in the potential path to commercialization. An SPA "does provide clarity and predictability on the regulatory issues going forward," Gould said in summarizing the SPA's key benefit. In comparison, he said that the traditional regulatory pathways of a series of trials often are unclear. Though all hurdles may be negotiated, questions still often remain concerning specific indications and marketing claims. He said that in particular the blood substitute sector has shown "a fair amount of uncertainty" and that it has been "quite confounding to try to bring some predictability and clarity to our own particular process."

Gould characterized the SPA, by contrast, as "an agreement, a written document, part of the administrative record, in essence a contract that can't be changed unless both sides agree [to changes]." The SPA that Northfield has struck with CBER in particular covers "the primary basis for an efficacy claim," which in turn controls specific marketing claims, which are often unclear in traditional regulatory processes, Gould said. He estimated that only a very small number of SPAs have been granted by CBER and so termed the agreement "a true milestone" and a "cornerstone" of Northfield's current regulatory strategy.

The Phase III trial the SPA covers is one that has a variety of unique features to it as well. The "prehospital" terminology describing the study means use of PolyHeme by first responders carrying the product in ambulances and comparing the effects of administering the blood substitute to the effects of standard administration of saltwater. Transfusable blood cannot be used in ambulances because of compatibility issues and insufficient time to do appropriate testing, Gould explained, while PolyHeme requires no crossmatching, since it is compatible with all blood types. About 720 patients will be randomized to the two groups.

One issue to be addressed is that of patient consent, since emergency situations often mean that patients are in no condition to provide consent. To deal with this, Gould said that the Institutional Review Boards (IRBs) in areas where the trial will be carried out are holding community meetings to disseminate details of the study protocol, which is approved by the FDA for emergency research, but requires positive feedback concerning the administration of PolyHeme when consent cannot be given. He said that the IRBs would use various means to gather a consensus on the trial from groups that represent the potential trial population. He said that the initial meetings have provided strong support for the protocol.

Gould projected that a two- to three-year pathway to clearance presents a problem, since Northfield's current burn rate will take it out to only six or nine more months. And the new trial "is going to be expensive" requiring at least $15 million, he predicted. "We're pursuing a number of options with regard to fundraising," Gould said, noting that the SPA agreement should provide a major boost to those efforts. "We think this will be particularly valuable, very, very helpful in allowing us to solidify our plans and raise funds in the near future. It should have a large, positive impact on the business side."

Sensant unveils Silicon Ultrasound images

Sensant (San Leandro, California) unveiled the first Silicon Ultrasound images taken in a clinical setting at the recent World Federation of Ultrasound in Medicine and Biology meeting in Montreal, Quebec. The company said the images "demonstrate an improvement in the ability to capture and display diagnostic information" when compared with images with conventional piezoelectric transducer technology. For the time being, Sensant CEO Igal Ladabaum told BBI, the company will continue with demonstrations of "clinical viability." Ultimately, Sensant will seek a 510(k) approval from the FDA, which it hopes to receive within the next 18 months to two years.

In its quest to demonstrate clinical viability, Sensant said Silicon Ultrasound images of carotid anatomy "clearly depict the intima, the lumen's innermost layer." The ability to see this image enables physicians to get an early indication of a patient's risk for cardiovascular disease and stroke. Ladabaum said Silicon Ultrasound provides "a more informative image, so physicians can make quicker and better decisions." The company also is working on high-frequency probes for breast imaging, musculoskeletal imaging and convex general abdominal imaging.

"The high-frequency imaging made possible by Sensant's silicon technology provides the ability to resolve detailed anatomical structures and to better characterize lesion boundaries, thereby broadening ultrasound's suitability for applications usually reserved for more expensive imaging modalities, including magnetic resonance and computed tomography," the company said.

The technology involves what the company calls "tiny silicon MEMS structures" known as capacitive microfabricated ultrasonic transducers, or cMUT. The cMUTS "resemble tiny silicon drums, each smaller than the width of a human hair, fabricated on the surface of a silicon wafer," according to Sensant. Ladabaum said the important aspect is the "bandwidth of the transducers" and that the technology can be used "over a wide range of frequencies" and offers both contrast agent imaging and harmonic imaging. The technology was originally developed at Stanford University (Palo Alto, California), and Ladabaum was basically required to license back his own patents from the university. However, the company has a "substantial intellectual portfolio beyond the Stanford technology," he said.

Clinical viability is available for technology that are basically probes that can be added to any existing ultrasound device, but the company also is moving beyond 2-D into 3-D imaging. "We have both existing technology and technology that's just around the corner," Ladabaum said. "The most important thing we will be doing is finalizing the development of our 3-D platform," he said, adding that it will be about two years before clinical results are available.

At the moment, the company is considering its distribution options. And while neither the 2-D nor the 3-D imaging is commercially available now, Ladabaum expressed confidence in the company's ability to influence "purchase decisions" and ultimately prevail in "swinging market share" to its products. "Certainly, physicians will want to have the probe" because of the superior images it offers, Ladabaum said.