By MARK McCARTY
Medical Device Daily Washington Editor
SAN FRANCISCO Now that the first generation of drug-eluting stents has more or less found its way into medical history and the bioresorbables are still grinding out clinical trial data, the time is apparently ripe for a firm that has staked its future on a dual-elution design to clamp down on restenosis and thrombosis.
What is not clear yet is whether the Combo stent, made by OrbusNeich (Hong Kong), will pass an FDA scrub-down upon completion of a pivotal study. The company has yet to snare an investigational device exemption from the agency, but the Combo is related to several of the firm's stents that use the endothelial progenitor cell (EPC) capture technology that is at the heart of this device, and those other stents are now available in roughly 60 countries, although they lack the anti-proliferative element found in the Combo.
The company unveiled preliminary study data for the Combo at this year's edition of Transcatheter Cardiovascular Therapeutics, and the idea behind this dual-elution stent is that the use of EPC capture, which the firm has dubbed Genous, will help speed up healing of the endothelial surface while the firm's choice of anti-proliferative, sirolimus, tamps down on excess neointimal proliferation. The stent elutes sirolimus only from the surface that contacts the vessel, while the Genous matter is evenly distributed around the entire surface of the stent.
Genous is based on the CD34 antibody, which serves as the mechanism of capture for EPCs, which in nature are triggered by infarcts and act to heal the endothelium. The talk at TCT was that the firm's data indicate the device provided 70% strut coverage in less than 50 days and full coverage at 140 days. Orbus' formal Nov. 10 statement offers a finer bit of detail, indicating that the mean percentages of covered struts "were 74.4% at two months, 84% at three months, 87.4% at four months and 95.6% at five months." The statement also indicates "no major adverse cardiac events were recorded."
One of the potential flies in the ointment for this EGO-COMBO study is that it relies on optical coherence tomography (OCT), which is not seen as a particularly robust modality for distinguishing between the various tissue types that inhabit the interior of the coronary vasculature. The EGO-COMBO data are described as "interim results" from a study examining stent coverage of 87 stents implanted in 60 patients, and those interim data come from scans of 40 of those patients at intervals between baseline and five months. The data set covers more than 7,000 OCT frames depicting more than 60,000 struts, the statement notes, a data set that is driving optimism at the firm regarding the Combo's ability to do what other metal-strut stents have heretofore failed to do.
Medical Device Daily asked David Camp, Orbus' VP for sales and marketing, what the company thinks it might propose to FDA regarding the indication for the Combo, but Camp said, "I don't think we have it narrowed down" as yet.
Regarding the problem with OCT's imaging, Camp indicated the firm is optimistic that this fly-through-the-tunnel imaging technology will provide enough data to ensure the vessels are lined with the right stuff. "I think OCT will be the difference for our stent," he said, although he also said "we're very aware of the fact that there's no consensus" as to what the images say about a coronary artery. "We're working with the top doctors to develop a standard" for interpretation of those images, he said.
Camp confirmed that the stent is a metal construct that is rectangular in cross section, and indicated that the nagging issue of duration of anti-platelet therapy dual or otherwise is still on the table. "I don't think we're going to recommend any kind of" anti-platelet (APT) therapy, he said, stating that the company's policy will be to "let the doctors handle it via guidelines." One benefit of this stent, he said, will be to "provide a comfort level that if [physicians] need to pull a patient off [dual] APT" for any reason, "that it won't be a catastrophic event."
As for the status of the device's IDE filing, Camp said Orbus has had "several meetings with FDA this week" and hopes to start enrolling the pivotal trial by late 2012 or early 2013. Camp hinted that the company is on the same wavelength as some members of the interventional cardiology devices branch at FDA where harmonization-by-doing (HBD) with regulators in Japan is concerned. FDA staff and several others appeared earlier in the week at TCT to discuss HBD, and one of the panelists said that while full-blown harmonization is an impossible dream, some sort of convergence is not so difficult (Medical Device Daily, Nov. 9, 2011). The author of this observation, Mitchell Krucoff, MD, of the Duke Clinical Research Institute (Durham, North Carolina), was heard to say at least twice at TCT 2011 that he sees the good clinical practice guidelines in effect in the U.S. and Japan as functionally almost identical.
"We're trying to design a pivotal trial that covers Japan and the U.S. that will enroll 2,000 to 2,500 patients," Camp said, adding that Orbus expects to win a CE mark for the Combo by 3Q12.
Camp indicated that the pivotal trial will likely entail a 12-month clinical and a five-year total follow-up. The first year will include angiography and OCT imaging studies, but the next four years will consist of more routine clinical assessment. As for the device's numbers in pre-clinical testing, he said, "we have a paper [which] shows no [late-stent thrombosis], and better anti-proliferation" than Xience, the DES offering from Abbott (Abbott Park, Illinois). Camp said his company's animal models are "all porcine right now, and some rabbit iliac" testing out to 180 days. "All the pre-clinical we did was according to FDA guidelines," he added.
Medical Device Daily asked whether the firm is considering asking for premium pricing from U.S. payers and whether that would require a new technology add-on payment from CMS. Camp said it is too early to say for certain. However, the firm's reimbursement plans are a bit more certain where the European market is concerned. "The big one we're going after is France," Camp said, although he noted that the BeNeLux nations, the UK, Germany and others will be approached.
"France is a great market," for reimbursement because the payment levels are healthy compared to most EU nations, Camp said, but "you have to do a little extra work to get reimbursement." However, he said the extra effort pays off thanks to the practice of reference pricing still in common usage in EU nations.
Published November 14, 2011