Testing somewhat unfamiliar waters, heart valve maker Edwards Lifesciences Corp. began clinical testing of a compound designed to stimulate the growth of blood vessels.
The Irvine, Calif.-based company began a Phase I/II trial to evaluate the ability of a product labeled EW-A-401 to stimulate the natural growth of normal blood vessels in treating intermittent claudication, a symptom of peripheral artery disease that is caused by poor blood flow in the legs. The compound encodes a zinc finger DNA-binding protein transcription factor designed to activate all isoforms of the vascular endothelial growth factor-A (VEGF-A) gene to promote angiogenesis.
"This is a strategic move and a logical extension of our company's main focus, which is treating advanced cardiovascular disease," Barry Liden, Edwards' director of global communications, told BioWorld Today. "In this case, we believe the compound ultimately could have possible use in ischemic cardiac disease. To get into that part of the body, there will need to be a device delivery system. We have some concepts for some possible technologies that could marry the biotech compound and a device to obtain an effective therapy that could treat and expand a much larger market of patients."
He declined to provide details on the delivery system, though its use would come into play later in EW-A-401's development as Edwards looks toward additional indications for the therapy such as critical limb ischemia and ischemic heart disease. In the initial phase of testing, the compound is being administered by way of an intramuscular injection into a patient's leg.
Treatment began last month with the enrollment of the first patient at the Warren Grant Magnuson Clinical Center of the National Institutes of Health in Bethesda, Md. Designed as a double-blinded, placebo-controlled, dose-escalation study eventually involving 36 patients, the study seeks to measure EW-A-401's safety in treating intermittent claudication. Investigators also might gain preliminary data on the therapy's effectiveness in improving patients' blood flow, walking capacity and quality of life.
Edwards expects the trial to take between 12 and 18 months to screen and enroll patients, with an additional six months of safety follow-up. The NIH is funding the study.
"With this product, we have figured out the right keys that unlock the lock to actually get a gene to decide to start growing blood vessel," Liden said. "What that will help do in the leg, hopefully, is to get more oxygen to the muscle tissue and help cure the patient of the symptoms of the disease."
Down the road, Edwards hopes that further development demonstrates the compound's ability to repair cardiac tissue damaged by a heart attack.
The company licensed EW-A-401 from Sangamo BioSciences Inc., which originally developed it as part of a multiyear research alliance between the companies to develop gene-regulation technologies to treat cardiovascular disease. In preclinical studies, the compound was shown to be effective in stimulating growth of functionally normal vessels and increasing blood flow in ischemic limbs.
Richmond, Calif.-based Sangamo received a $1.4 million payment in 2001 upon delivering the compound to Edwards. Sangamo gained an additional $1 million when the drug's investigational new drug application was filed earlier this year, and Liden said Sangamo would be eligible for additional downstream milestone payments, though he declined to provide specifics.
Edwards, which produced the world's first commercially available heart valve in 1960, has no plans to partner any further development work on EW-A-401 as it moves the compound forward. But Liden said the company, which also produces cardiac monitoring systems, is involved in similar deals to develop compounds that could work in concert with its devices, though none of the other collaborative work has been publicized.
"We are open to and believe that the future of medical therapies involves the combination of drugs and devices," he added. "We are actively exploring those opportunities in other areas."
On Tuesday, Edwards' stock (NYSE:EW) gained 35 cents to close at $35.31. Sangamo's shares (NASDAQ:SGMO) rose 9 cents to $4.34.