ViroMed Co., Ltd. of Seoul, Korea, has completed the first cohort of three patients in the first clinical study of VM202, a novel gene-based therapeutic drug for the treatment of critical limb ischemia, under the direction of Dr. Timothy Henry, an Interventional Cardiologist and Director of Research at the Minneapolis Heart Institute Foundation. A Data Safety Monitoring Board reviewed the data from the first cohort and recommended to the next dose escalation cohort.
Peripheral arterial disease (PAD) is usually caused by atherosclerosis in the arteries of the lower extremities, resulting in ischemic limb disease. About 250,000 people are hospitalized with PAD in the United States each year, usually for lower limb ischemia. Critical limb ischemia (CLI) results from severe obstruction of arteries due to advanced PAD. Amputation is required in about 150,000 of these patients annually when angioplasty or bypass surgery fail. Their prognosis after amputation is poor, with mortality ranging between 5 to 20%.
Treatment for CLI is directed at restoration of blood flow to affected areas through regenerative angiogenesis. In patients developing a gradual obstruction in arterial blood flow, new collateral vessels appear to provide tissue perfusion and relieve clinical symptoms. The term ˝therapeutic angiogenesis˝ was coined to describe intervention used to stimulate or induce new blood vessel growth by administering angiogenic factors, either as recombinant protein or by gene transfer, to the ischemic sites.
Therapeutic angiogenesis represents a novel strategy for the treatment of cardiac and vascular diseases. Viromed, a pioneer in developing novel therapeutic products for the treatment of important diseases, is the first Korean sponsor to launch such an important clinical program in the United States, and the first company ever to introduce this novel therapeutic into patients. The use of gene therapy products such as VM202 represents a potentially significant advance in this important area of medicine.
VM202 is a novel gene therapy product consisting of a proprietary plasmid vector encoding two isoforms of the hepatocyte growth factor (HGF) engineered as a novel therapeutic gene, HGF-X7. The key feature of HGF-X7 is that it was designed by inserting a series of intron sequences into certain sites of HGF cDNA so that both isoforms of HGF protein are expressed simultaneously and as efficiently as in the human genome. Because there was no change in the coding region of the HGF gene, HGF proteins generated from VM202 are identical to the wild-type human HGF proteins.
ViroMed selected the Minneapolis Heart Institute at Abbott Northwestern Hospital as the clinical site for the first clinical evaluation of its novel angiogenesis product, VM202, in the United States, under the direction of Dr. Timothy Henry, an Interventional Cardiologist and Director of Research at the Minneapolis Heart Institute Foundation. The Foundation acts as the research, education and philanthropic arm of the Minneapolis Heart Institute, internationally recognized as one of the world`s leading heart institutes. The Foundation promotes aggressive discovery through clinical physician-driven research and effective educational programs. As a regional and national leader, they are expanding knowledge of cardiovascular medicine and building the next standard for patient care.
Experimental results in an ischemic limb rabbit model with VM202 provided powerful evidence of the effectiveness of VM202. The U.S. Food and Drug Administration, as part of its decision to allow the proposed clinical study to move forward without holds, reviewed this rabbit model data, together with extensive nonclinical safety and robust preclinical efficacy data, as part of an Investigational New Drug Application the FDA allowed in November 2006.
Cardiovascular gene therapy data to date have shown no clinically significant evidence of inflammatory or other complications, and appears to be safe and well tolerated. The objective of the Phase I clinical study of VM202 at the Minneapolis Heart Institute is to monitor safety and to evaluate VM202 therapeutic benefit for patients with critical limb ischemia by increasing blood flow in lower extremities.
The Phase 1 trial of VM202 will enroll, treat and evaluate 12 patients who have critical limb ischemia that has not responded to standard therapies. The protocol will require approximately 19 months to complete treatment and evaluation each in each of 4 dose cohorts with 3 patients in each cohort. VM202 doses of 2, 4, 8 or 16 milligrams will be administered by intramuscular injection to the ischemic tissue. To support study objectives of safety, tolerability and preliminary efficacy, a review of safety parameters of each dose cohort will be completed prior to escalating to the next highest dose cohort. In addition to rigorous safety assessments, efficacy evaluations will include measurements of blood flow and oxygen perfusion in the affected ischemic tissues.