The Abbott Vascular Devices (Redwood City, California) division of Abbott Laboratories (Abbott Park, Illinois) reported in mid-September that it had enrolled the first patient in its ZOMAXX I drug-eluting coronary stent clinical trial. ZOMAXX I is a 400-patient, randomized clinical trial that will be conducted in more than 30 centers in Europe, Australia and New Zealand.
The study will compare Abbott's ZoMaxx drug-eluting coronary stent to Boston Scientific's (Natick, Massachusetts) Taxus Express2 drug-eluting stent (DES), with a primary endpoint of nine-month in-segment late loss. Enrollment is expected to continue through the first quarter of 2005, the company said.
"The initiation of the ZOMAXX I clinical trial represents a significant milestone for our organization," Robert Hance, president of Abbott Vascular Devices, told Cardiovascular Device Update. "Along with our plans for a North American pivotal trial, the start of ZOMAXX I demonstrates our commitment to becoming a leading player in drug-eluting stents, one of the fastest-growing areas in medical technology."
Robert Whitbourn, MD, of St. Vincent's Hospital (Melbourne, Australia), who enrolled the first patient in the ZOMAXX I trial, said he is looking forward to enrolling additional patients in this trial. "Based on in vitro studies, the ZoMaxx stent design demonstrated excellent flexibility, contributing to a high level of deliverability. I am eager to test the device clinically," he said.
The ZoMaxx stent used in this study consists of three key components: the drug, the stent platform and the polymer carrier. The drug, ABT-578, is an immunosuppressant discovered and synthesized by Abbott scientists. It inhibits inflammation and proliferation of smooth muscle cells, both key targets in treating restenosis. In animal testing, when compared to similar compounds, ABT-578 has been shown to be highly lipophilic (allowing a greater concentration of drug to penetrate the tissue). It is in the same family as rapamycin, used by Cordis (Miami Lakes, Florida) in its DES program, as well as Guidant's (Indianapolis) everolimus compound.
The second component for ZoMaxx is the underlying stent platform – the TriMaxx coronary stent, which is currently under CE mark review as a non-drug-eluting stent. The company said it believes the TriMaxx will be the next evolution in metallic stents with its tri-layer composite of stainless steel and tantalum, and its ultra-low crossing profile – designed to facilitate placement of the stent in the artery. The tri-layer composite material allows for extremely thin struts while maintaining optimal visibility via angiography. The stent also features a unique stent pattern with Apex Ring Control, which is designed to maximize flexibility and deliverability while maintaining ideal scaffolding and vessel wall coverage for uniform drug delivery.
The third important component of the device is the polymer coating for the stent, called Pharmacoat. The compound is a formulation of phosphorylcholine polymer coating, which Abbott acquired a license to use when it purchased Biocompatibles International's (Farnham, UK) cardiovascular stent business in May 2002 for $243 million. Phosphorylcholine is a polymeric replica of the outer surface of a red blood cell that acts as a biologically inert coating that resists clot formation in vitro. Pharmacoat is a specific formulation of phosphorylcholine that contains an extra cap-coat – an additional layer of coating that enables the drug to elute over time. In vitro studies show that Pharmacoat acts as a versatile drug-eluting vehicle that provides a stable foundation for the slow, controlled release of ABT-578, the company said. Since 1996, 150,000 non-drug-eluting, phosphorylcholine-coated stents have been implanted worldwide.
Interestingly, ABT-578 is currently being licensed to Medtronic (Minneapolis) for its own DES program. Both Medtronic and Abbott use the Pharmacoat stent coating. Additionally, the Abbott device incorporates a balloon and catheter delivery system from Medtronic into its platform. "It's an interesting relationship [with Medtronic]," Hance told CDU, "both a collaboration and a competition at the same time."
While he noted that the two companies use the same drug and coating, "we have our separate drug-eluting stent programs and clinical programs and operate independently." That being said, Hance said that both companies hoped that by "putting their horsepower behind this one drug compound, we think there will be some synergies for both parties as we advance."
At this point, Abbott does not plan to market its Dexamet (dexamethasone-eluting) stent in the U.S., a DES for which the company already received the CE mark in February 2003, "although it has some very intriguing characteristics to it that could factor into some of our R&D decisions" Hance said. The Dexamet was the second DES on the European market.
Hance said Abbott believes the design of the ZoMaxx system will "stand very well" in deliverabilty, enabling doctors to get to difficult-to-reach lesions. From a historical perspective, he said that the shifts in the stent market "have really moved because of the deliverability of the products. We think that's an important differentiator."