Diane Dottavio, PhD, notes that there is a basic, inescapable fact about the new drug-coated and drug-eluting stents a fact frequently overlooked. Dottavio, vice president of research and development for Endovasc (Montgomery, Texas), points out that when the drug is used up, the stent remains and stays as a foreign body in the vasculature. The resultant problems can be numerous, she told The BBI Newsletter. "With the stent there, the body may still detect a problem, problems with the way the repair has been done, or cells not aligning properly so there is late remodeling, or an inflammatory process occurring." The result could be late development of restenosis or other problems, showing up with longer-term use and longer-term studies of these stents, a technology still only proven successful in shorter-term trials.
Endovasc and its partner, TissueGen (Arlington, Texas,) propose an elegantly simple and superior alternative: that after the drug is gone from the stent, the stent also disappears, reabsorbed by the body. "This is the Holy Grail," says Dottavio of such a strategy and the technology to achieve it. And pursuing this goal is the focus of a new joint venture announced this past summer by the two companies, the j-v named Endovasc-TissueGen Research Sponsors. The purpose of the new subsidiary company is to combine the drug work being developed by Endovasc with the stent engineering expertise of TissueGen to create a line of drug-eluting cardiovascular stents that then are resorbed by the body, leaving a totally patent, healthy vessel.
TissueGen's contribution is its exclusive license to patents relating to the composition and manufacture of bioresorbable, drug-releasing polymeric materials that were developed by its president and chief scientific officer, Kevin Nelson, PhD, with that technology developed at Nelson's laboratories at the University of Texas at Arlington. Endovasc's contribution is the co-licensing of its patented, time-released drug, prostaglandin E-1 (PGE-1) to be used with the bioresorbable stent.
As part of the agreement, Endovasc will purchase a $150,000 convertible promissory note from the joint venture. The majority of these proceeds will be used to fund development of the prototype stent, that effort to be headed by Nelson. The companies also will seek to raise up to another $2.5 million from third-party investors, in exchange for membership interests in the j-v, those funds going to support clinical trials and eventual commercialization.
Endovasc also has developed another drug-coating technology called PROStent for coating of bare metal stents, an effort that is in a preclinical trial phase. But Dottavio notes that this effort is likely to be outlicensed to other stent manufacturers, since this in-house effort will be preempted by the work of Endovasc-TissueGen Research Sponsors and its emphasis on resorbable materials.
With success of the resorbable drug/stent technology in peripheral and coronary applications, Dottavio says, "Our future development will be in all kinds of stents stents that keep vessels and all kinds of things open, urinary vessels, neurological, whatever. This is just the beginning."
Technology brings X-ray inspection of devices
We all know about humans who undergo X-rays, but what about medical devices that undergo X-rays? Glenbrook Technologies (Randolph, New Jersey) is developing X-ray inspection systems for the purpose of checking the production quality of implantable medical devices, and avoiding the poor quality potentially harmful to patients. With a client list that includes U.S. Surgical (Norwalk, Connecticut), Boston Scientific (Natick, Massachusetts) and Martek (Columbia, Maryland), Glenbrook says its real-time X-ray camera is the heart of its technology. "We have the unique technology of building X-ray detector devices that, in effect, perform as X-ray microscopes," Gil Zweig, president of Glenbrook, told BBI's sister publication, Medical Device Daily. "This is a very unique capability."
In the case of U.S. Surgical, where titanium staples are being loaded into the surgical stapler head, "they need constant reassurance that every staple that is supposed to be there is, in fact, in place," Zweig said. Another example, in the case of Martek and companies like it, bifurcated and trifurcated catheters are made that are used in dialysis and similar applications. Inside the device, there is a plastic molded component that is essential to the device in that it should not contain voids or bulges. Otherwise, blood could collect in the void and begin to form a clot, which could be released into the bloodstream.
Prior to the availability of Glenbrook's X-ray technology, the only alternative was to cut the device open and inspect it. "Some manufacturers will do 100% inspections; other manufacturers will do an audit of a lot to make sure that all of these production parameters, whatever they may be, are producing a uniform and consistent product," Zweig said. Glenbrook Technologies was formed in 1983 for the purpose of providing X-ray capability to the electronics industry, such as with printed circuit boards. It began selling to companies in the medical device industry about 10 years ago. The technology uses a "continuous operating, comparatively low-power X-ray source," Zweig said.
For medical applications, the X-ray is pulsed, "just a quick burst," he said. In these applications the device generates a continuous but lower-power X-ray so that the object itself can be moved around and observed continously. "We can look at small areas of an object" and magnify it on the video monitor 20 times. What's especially helpful about the technology in terms of medical devices, too, is that it can image soft materials, like polymers, silicones, rubbers and ceramics."
Recently, the company has added what it calls the Dual-VU inspection capability, enabling the acquisition of a "simultaneous, congruent, optical image of the medical device being inspected," the company said. Both the image of the outside of the device magnfied and the X-ray image are presented on video monitors that are side-by-side, and underneath on a lower shelf of the equipment is the actual device being X-rayed, so it really offers three images, Zweig said.
Possis halts Phase I TIME trial
Possis Medical (Minneapolis, Minnesota) ended its Phase I TIME (Thrombectomy in Middle Cerebral Embolism) clinical trial for ischemic stroke in August after study investigators decided that the company's device, the Angiojet NV 150 neurocatheter, did not demonstrate sufficient efficacy. However, Possis' top executive said research into other possible remedies would continue. The study investigators, who according to Possis, "included some of the world's leading clinicians and researchers in treating ischemic stroke" that is, stroke caused by a clot or other material lodging in the middle cerebral artery determined that the Phase I results did not suggest moving into a Phase II trial. Overall, the device effectiveness at delivering thrombectomy, or clot removal, was approximately 30%.
Robert Dutcher, chairman, president and chief executive officer of Possis, said in a statement, "While we are disappointed in the short-term outcome [of the trial], we are resolved to continue our research efforts along several paths, including using drugs and our device together, to discover a therapy with the right balance of safety and effectiveness." It was the conclusion of the study investigators, and Possis agreed, that the NV 150 neurocatheter, while safe, had not met the clinical challenges of being effective enough to warrant a Phase II trial.
Possis, which manufactures devices for the cardiovascular and vascular treatment markets, said the challenge in treating this type of stroke is to intervene rapidly from symptom onset (within six hours), and to be safe, while also rapidly and effectively removing the material blocking blood flow. The company said that at present, the therapies available to clinicians for treating stroke victims, along with the requisite infrastructure, are not very advanced when compared to treatments available for heart attacks. Dutcher said, "Effective future stroke treatment will likely require combination therapies, along with significant commitments to community support and improved medical reimbursement. We hope to help bring about this future through our continuing R&D and market development efforts." Possis markets the AngioJet Rheolytic Thrombectomy System in the U.S. for blood clot removal from coronary arteries, leg arteries, coronary bypass grafts and AV dialysis access grafts.
The company said the ending of the TIME trial would not have any revenue or earnings impacts on its previous forecasts for fiscal 2004. Possis still expects full-year revenues in the range of $72 million to $75 million, and diluted earnings per share in the range of 54 cents to 64 cents a share.
Impath files for bankruptcy
Embattled cancer information and analysis firm Impath (New York) said late last month that it and its subsidiaries have filed voluntary petitions for reorganization under Chapter 11 of the U.S. Bankruptcy Code in the U.S. Bankruptcy Court for the Southern District of New York. The purpose of the filing is to facilitate the company being able to conduct business as usual while it develops a reorganization plan, it said.
In conjunction with the petitions for Chapter 11 reorganization, the company said it would ask the bankruptcy court to consider a variety of "first-day motions" to support its employees, vendors, customers and other constituents. These include motions seeking court permission to continue payments for employee payroll and benefits, obtain interim financing authority and maintain cash management programs, and retain legal, financial, investment banking and other professionals to support the company's reorganization actions.
In connection with the Chapter 11 filings, Impath is seeking bankruptcy court approval of a $15 million debtor-in-possession (DIP) financing facility to be provided by Fleet National Bank, as agent and lender, and other pre-petition secured lenders. If approved, up to $3 million of the new funding will be available immediately on an interim basis (pending final approval of the full $15 million financing facility) to supplement the company's existing capital and help it fulfill obligations associated with operating its business, including its employee payroll and payments to vendors for goods and services provided after the filing.
The DIP financing facility is conditioned on the company engaging in a process to sell its core and non-core businesses. In addition to the sale efforts, the company will explore other possible restructuring alternatives during the Chapter 11 cases, including the potential for a stand-alone plan of reorganization.
"After reviewing all of the options available to us, we determined that voluntarily filing for Chapter 11 protection provided us with the time to develop a comprehensive plan of reorganization," said Carter Eckert, chairman and chief executive officer. "It facilitates the company being able to conduct business as usual so that we may maintain the quality and availability of our products and services."
The company reported the resignation of James Agnello, chief financial officer and senior vice president. He will continue as a consultant to assist Impath in its transition period following the bankruptcy filing.
Impath is in the business of improving outcomes for cancer patients. The company is a source of cancer information and analyses with a database of more than 1 million patient profiles and outcomes data on more than 2.3 million individuals. Impath Physician Services provides patient-specific cancer diagnostic and prognostic information to more than 8,700 pathologists and oncologists in more than 2,100 hospitals and 630 oncology practices.
NMT reports settlement of arbitration
NMT Medical (Boston, Massachusetts), a developer of catheter-based technologies for treating cardiac sources of stroke, reported settlement of its outstanding arbitration with Bio-Tech Engineering (BTE), Ferenc Schmidt and the estate of Kevin Maughan. In its demand for arbitration filed on June 1, 2002, BTE sought $10 million for alleged breach of its performance obligations to manufacture and market surgical clips and mini-clips pursuant to a license and technology agreement.
As part of the settlement, NMT and BTE have terminated the license and technology agreement, NMT has acquired certain patent applications, patents and patent rights related to these clip products, and NMT has paid $950,000 to BTE, which also has agreed to a general release of any and all claims against NMT.
PainCare establishes surgical centers unit
PainCare (Orlando, Florida) said that in response to strong and growing demand from its national network of pain management practices and MedX-Direct rehabilitation program partners, the company has formed PainCare Surgical Centers, a wholly owned subsidiary established for the purpose of acquiring, developing and operating high-tech, outpatient surgical centers dedicated to performing minimally invasive spine surgery and associated pain management procedures. PainCare has appointed Jay Rosen, MD, a member of the company's board of directors with experience in developing and operating outpatient surgical centers, to serve as president of PainCare Surgical Centers.