Is the drug-eluting stent (DES) in more trouble?
That could be the case, according to a new study just unveiled byCook Medical (Bloomington, Indiana), that study indicating the positive effects of Resten-MP in preventing restenosis in patients implanted with a bare-metal cardiovascular stent.
Results of Cook's APPRAISAL trial suggest that a drug delivered to a patient following stent placement may be just as effective, or more so, than a drug attached to and eluting from a stent device, thus perhaps bypassing the need for the device/drug combo.
Phase II of the trials were held in Germany and France and enrolled about 52 patients taking part in the six-month-study. The patients suffered from symptomatic ischemic heart disease and the stenotic lesion of native coronary arteries. About 80 % of the patients in the study were type B2, C-lesions — some of the more serious cases in cardiovascular illnesses.
In the study, clinicians administered Resten-MP within 60 minutes of successful stent placement in the coronary artery, and again 24 hours later via slow-push intravenous administration.
Resten-MP (AVI-4126) was developed byAVI BioPharma (Portland, Oregon) and licensed by Cook Medical. It is a third-generation antisense agent that targets the key regulatory gene involved in cardiovascular restenosis.
"We're putting in a bare stent [as opposed to a drug eluting stent], Joe Horn president of Global Therapeutics , a subsidiary of Cook Medical, told Medical Device Daily. "The delivery system is system is through microparticles or microbubbles. The bare stent bonds with the tissue."
The methodology offers a challenge to DES technology which has been hit over the past year with a series of studies indicating increased levels of thrombosis — in some cases resulting in slightly increased rates of mortality — and a general pullback in some hospital practices from 90% DES use in all stenting to as low as 60%-70% in some cases.
Besides impacting the current range of first-generation of DES devices, the finding for Resten-MP may cast a shadow over the prospects of second-generation DES devices poised to come online.
"The latest clinical trial results are really promising. We believe that the Resten-MP delivery system eliminates the potential long-term problems associated with the current drug-eluting stent systems available to physicians and patients," said Stefan Sack, MD, principal investigator at the University Of Essen in Germany (Duisburg, Germany), the study's main investigative center.
In some cases there has been a tendency for clots to form at the site where the stent damages the arterial wall. Typically when the drug is completely eluted, clotting could then occur.
Horn told MDD that if the initial positive result "plays out [in future trials] it would be a monumental change in treating cardiovascular problems," Horn told MDD. "We are currently planning for European CE Mark approval."
The process for this approval could start in the 4th quarter of this year, he said.
Horn declined to go into detail about the specifics of the study results or when the bare stent/drug protocol could come to the U.S. but that there are plans to seek FDA approval.
"We are looking forward to the presentation at the Transcatheter Cardiovascular Therapeutics Conference [in Washington] this October," Horn said. "Our plan is to invest the necessary resources to commercialize AVI's Neugene technology as quickly as possible for the cardiology market. Our partnership with AVI BioPharma has proven to be a successful collaboration as we seek alternative drug delivery methods to improve the efficacy shown by drug-eluting stents."
Cook Medical has worked jointly with Avi Biopharma on projects for a little more than a year.
Avi entered into an agreement with Cook Medical last year that called for Cook to license Neugene, an antisense technology for down-regulating c-myc gene expression in the field of cardiovascular disease (MDD March 13, 2006).
Other details of the deal included Cook taking over development of Avi's device-related programs for cardiovascular disease. Cook purchased 692,003 shares of AVI common stock for $5 million under a stock purchase agreement. Cook took control of AVI's facilities and personnel at its Colorado site.
Cook Medical says that it is the first company to introduce interventional devices in the U.S. Today, the company participates in all global markets, integrating device design, biopharma, gene and cell therapy and biotech to enhance patient safety and improve outcomes.