Medical Device Daily Associate
GenVec (Gaithersburg, Maryland) 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 Rigshospitalet, and Erik Botker, MD, at the Skejby Hospital (Aarhus, Denmark). The company said it expects 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 BioBypass is more than that.
He told Medical Device Daily 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," Fischer said. "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," he said.
Fischer said that the BioBypass product enjoyed a long and colorful history.
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.
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.
GenVec is also developing treatments for cancer and vision loss and vaccines for infectious diseases.