GenVec (Gaithersburg, Maryland) last month reported the launch of a Phase IIB randomized, placebo-controlled trial of its BioBypass angiogen for the treatment of severe coronary artery disease. The NOVA (NOGA Delivery of VEGF for Angina) trial will evaluate the effects of BioBypass on exercise tolerance, heart function, symptoms and quality of life in about 129 patients suffering from moderate to severe chest pain due to advanced coronary artery disease. Jens Kastrup, MD, at Rigshospitalet (Copenhagen, Denmark), is the principal investigator for the NOVA trial. Two medical centers have begun enrollment, under the direction of Erik Jorgensen, MD, at Rigs-hospitalet, and Erik Botker, MD, at the Skejby Hospital (Aarhus, Denmark). The company said it ex-pects about 15 centers in Europe and Israel to participate in the NOVA study.

BioBypass promotes production of GenVec's unique form of vascular endothelial growth factor (VEGF) to stimulate the growth of new blood vessels in areas of the heart lacking sufficient blood flow. This condition, known as ischemia, triggers chest pain in patients with severe coronary artery disease. While technically a gene therapy, company president and CEO Paul Fischer said that that BioBypass is more than that. He told Cardiovascular Device Update that the drug "is basically a DNA carrier," with the carrier being an adenovirus with the replication genes removed. Into that piece of DNA is placed the VEGF gene. "It turns out that the heart muscle happens to have a lot of receptors on it that make delivery of this adenovector into the heart muscle very efficient. Then the vector transiently expresses the VEGF gene in about two weeks." That in turn helps to generate the formation of new blood vessels in the target area, he said.

In an earlier Phase II randomized, controlled, multi-center trial known as the REVASC study, BioBypass was administered during surgery. The BioBypass-treated group showed significant clinical benefit, including an increased ability to exercise.

The NOVA trial is being conducted under a research collaboration between GenVec and the cardiology division of Cordis (Miami Lakes, Florida), a Johnson & Johnson (New Brunswick, New Jersey) subsidiary. BioBypass will be administered using the Cordis Noga technology with the Nogastar Mapping Catheter and Myostar Injection Catheter. The Cordis technology facilitates 3-D mapping of the heart, identifies ischemic tissue and allows for precise drug delivery, GenVec said.

Fischer noted that while many companies have attempted to use gene therapy for cardiovascular applications they have failed particularly, he believes, for one primary reason: "The main thing is delivery," he said, adding that until the Cordis system came along, the company was stuck on how to most efficiently deliver the drug into the myocardium. "We think that the delivery question has always been the key question. You need to have the protein produced long enough in the heart to produce the blood vessels."

The deal to develop BioBypass was first initiated in 1997 by GenVec and Warner-Lambert (Morris Plains, New Jersey). Pfizer (New York) then inherited the GenVec deal when it acquired Warner-Lambert in 2000. Since the start of the deal, Warner-Lambert/ Pfizer had spent upwards of $90 million on development and other costs associated with BioBypass, Fischer said. "But based on continuous review of their product portfolio including the products they acquired with Warner-Lambert it was determined that BioBypass did not fit with their overall drug development strategy." At the time that the product was dropped, the companies were in the midst of the REVASC Phase II trials, and there had been speculation that the results had not been efficacious enough to merit further support from Pfizer. However, Fischer said that wasn't the case. Indeed, he noted that the results of the study, which injected BioBypass via a surgical procedure into the heart muscle, "were really quite good."

While the arrangement with Warner-Lambert had been a good one, Fischer said that the change was fortuitous for his company, as GenVec was able to retain all development and commercialization rights for the product and would not have to share any future royalties generated by BioBypass with its former partner. After its partnership dissolution, GenVec decided that it needed a partner that had a medical device orientation. Enter Cordis. The companies partnered on a small study a couple of years ago on about 12 patients paring the Genvec's drug with the Cordis delivery system. "That actually looked to be very feasible," he said. In January of 2004, the companies formed a partnership to more fully explore the potential of those early studies' promising results. With the idea being that if the promising early results are borne out, a joint commercial venture would probably be formed.

Patients in the NOVA study are what Fischer termed "no option." While they do not have congestive heart failure, he said, they all have poor blood flow and have had one or more of the following: bypass grafts; multiple stent placements and maximum medical therapy. Aside from these no-option patients, Fischer envisions BioBypass being adjunctively administered to patients having a stent or bypass graft put in place into areas of the heart that cannot be revascularized. Another group that he sees as even more attractive is made up of patients with angina and administered a dose of BioBypass either in anticipation of a subsequent surgical procedure or to avoid the need for a future surgery.

Xtent gathers additional $25M

Xtent (Menlo Park, California) a developer of stent systems for delivering multiple stents and drug-eluting stent (DES) devices of customizable length with a single catheter last month reported closing on a new $25 million round of financing. The funding, Xtent said, comes from previous investors at a valuation of more than twice that of a previous financing round, closed in 2003. Xtent said that its DES system is designed to enable cardiologists to treat the largest, fastest growing portion of the market long, diffuse lesions, multiple lesions and multiple vessel disease with a single device which minimizes catheter exchanges. The Xtent System customizes stent length for each lesion treated and is designed to enable the cardiologist to treat complex lesions "rapidly, efficiently and with a high degree of accuracy," it said.

Gregory Casciaro, president and CEO, said that the company's key goal has been to differentiate itself from other stent and DES manufacturers in order to carve out a significant portion of this market, which he put at $6 billion by year-end 2006. The stent/DES sector, he told CDU, is increasingly seeing placement of multiple stents in each patient, so that Xtent has focused, instead, on a "one-catheter procedure" that at the same time provides for "multiple stent placements." He added: "The advantages here are many: the opportunity to save time for patients on the [surgical] table, reducing the amount of contrast dye necessary in treatment, [avoiding] the physician having to guess ahead of time the length of the lesion." The need to "guess" the lesion length and thus the particular stent to use has resulted in treatment failures ranging up to 40%, he said.

Explaining the Xtent approach, he said: "What we have come up with is the opportunity of delivering a stent train - up to 60 mm of stent - and divide it up according to the length of the lesions you are treating." After one length of stent is placed, the surgeon will then be able to deploy additional portions of this stent train to treat other lesions, but without using an additional catheter procedure. These multiple placements are carried out with the aid of real-time fluoroscopy that Casciaro said takes the "guessing game" out of selecting stents that he put at up to "26 variations for each of the [stent] manufacturers." This may result in "estimation errors" that can require additional and expensive stenting, he noted.

Brian Walsh, vice president, sales and marketing for Xtent, said that the price of the company's single catheter-multiple stenting procedure will be more than one stent placement but less than two stent placements. The result, he told CDU, would be savings on stent costs ranging from $300,000 yearly for smaller facility on up to $3 million yearly in a large teaching institution.

Casciaro said that the company expects to move forward with "in-man" clinical studies of the system in Europe "sooner vs. later" and definitely before the end of the year in order to pursue the CE mark, and commercialization to begin revenue flow during 2006. "In the process, we'll do a pivotal trial in Europe, mirroring what the FDA is going to require, to start building a clinical body of evidence to bring [the system] to the U.S.," he said. The company then hopes to gain commercial approval and begin sales in the U.S. by 2008.

CardioVascular Bio closes on IPO

Development-stage firm CardioVascular BioTherapeutics (Henderson, Nevada), reported concluding the sale of 1,725,000 shares of its common stock at $10 a share. The stock is now trading on the Over-the-Counter Bulletin Board under the symbol CVBT.

CardioVascular Bio is focused on developing a drug regimen for the treatment of cardiovascular diseases. Cardio Vascu-Grow, its main candidate, is a fibroblast growth factor that induces angiogenesis (blood vessel growth). When injected directly into the heart near affected arteries, Cardio Vascu-Grow has been shown to help repair the artery and increase blood flow to the heart. The company hopes to demonstrate that this regimen also will benefit the victims of stroke and diabetes.

The company filed its IPO registration statement with the Securities and Exchange Commission in September.

Vote set on Guidant/J&J merger

Guidant (Indianapolis) reported that it has set April 27 as the date for a meeting for shareholders to vote on the proposed mega-merger between it and Johnson & Johnson (J&J; New Brunswick, New Jersey). Shareholders of record as of March 21 will be entitled to vote on the deal.

The companies in mid-December reported their agreement in which J&J will acquire Guidant in a deal valued as worth about $24 billion. J&J will acquire the broad range of Guidant's cardiovascular technology and create a new medical device and diagnostic unit named Guidant.

Late July was set as a tentative date for closing the deal when it was first unveiled. The merger also remains subject to clearance under the Hart-Scott-Rodino Act and European Union merger regulations and other customary conditions.