VM BioPharma today announced the launch of the HI-PAD study, a trial to investigate the effect of VM202, a DNA plasmid encoding HGF, on mobility and calf perfusion in older adults with PAD.
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November 30th, 2017 – Chicago, IL– VM BioPharma, the United States division of ViroMed Co., Ltd in Seoul, South Korea (KOSDAQ: 084990), today announced the launch of the Hepatocyte Growth Factor to Improve Functioning in PAD (HI-PAD) study, a trial to investigate the effect of VM202, a DNA plasmid encoding hepatocyte grow factor (HGF), on mobility and calf perfusion in older adults with peripheral artery disease (PAD). This proof of concept trial will evaluate whether the gene therapy VM202 can improve symptomatic PAD, as measured by calf muscle perfusion using arterial spin labeling (ASL) cardiovascular magnetic resonance (CMR) for the first time in a study, walking performance, and skeletal muscle damage using calf muscle biopsy.
“Lower extremity peripheral artery disease is a common problem which severely impacts mobility and increases rates of functional decline in older adults. We are delighted to initiate this study, which may provide important information on the potential benefits of HGF gene therapy for PAD,” said Dr. Mary McDermott, MD, Jeremiah Stamler Professor of Medicine and Preventive Medicine at Northwestern University Feinberg School of Medicine and the principal investigator for the trial.
Lower extremity PAD, the narrowing of blood vessels in the legs, affects 10-15% of men and women age 65 and older and 15-20% of those 75 and older. Symptoms include painful muscle cramps when walking, climbing stairs or exercising; cool or cold feet and lower legs; and wounds on the feet that will not heal. VM202 is a plasmid DNA that contains the human HGF gene, which in vivo produces two isoforms of HGF proteins naturally found in the human body. HGF is a growth factor that induces angiogenesis and acts as a neurotrophic factor to the peripheral nervous system. After VM202 is injected into a patient’s muscle, it is taken up by cells which produce HGF protein. When released from skeletal muscle cells, HGF may induce new blood vessel formation locally by activating various signaling pathways. In this way, VM202 is believed to promote microvasculature and regenerate nerve cells, potentially engendering clinical benefit to patients with PAD. Currently, no medical therapies that improve calf muscle perfusion or reverse skeletal muscle damage have been identified, and few medical therapies exist for improving functioning in PAD patients.
“The National Institute on Aging, Dr. McDermott and her team are providing us with a unique opportunity not only to observe the implications on quality of life that VM202 may confer to PAD patients; but also to assess its therapeutic mechanism objectively with muscle biopsies and cutting edge arterial spin labeling CMR imaging,” adds Sunyoung Kim, DPhil, Chief Scientific Officer of ViroMed Co., Ltd. “PAD is a condition with significant unmet need; we believe that this study will yield important information on both understanding the physical and physiological pathology of PAD and its treatment.”
Study Design
The six-month, double-blind, randomized, placebo-controlled, single-center study is designed to assess the safety and efficacy of VM202 in 36 adult patients with symptomatic PAD, randomized to receive either VM202 or placebo. The primary clinical efficacy outcome will be the change in the six-minute walk at 3- and 6-month follow-ups. Secondary outcomes will include pain-free and maximal treadmill walking distance, calf biopsy measures of skeletal muscle regeneration, capillary density, and autophagy, physical functioning questionnaires, and MRI-measured calf muscle perfusion.
The study is funded by the National Institute on Aging.
About Peripheral Artery Disease (PAD)
PAD is a narrowing of the arteries of the legs, usually caused by atherosclerosis, or plaque build-up in the wall of vessels. Plaque is made up of deposits of fats, cholesterol and other substances. Plaque formations can grow large enough to significantly reduce the blood’s flow through an artery. PAD may cause pain when walking (claudication – most commonly in the calf), changes in skin color, sores or ulcers and difficulty walking. Critical limb ischemia occurs when there is severe loss of circulation to the legs and feet, resulting in gangrene and loss of a limb.
Ischemia-reperfusion injury in PAD leads to calf muscle oxidative stress and damage, which then induce reduced activity, smaller calf size, functional impairment and decreased mobility. Treatment options include lifestyle changes (smoking cessation and exercise), cholesterol-lowering medications, and revascularization. However, no medical therapies that improve calf muscle perfusion or reverse skeletal muscle damage have been identified, and few medical therapies exist for improving functioning in PAD.
About Dr. Mary McDermott
Dr. McDermott has over 200 publications to her name, with a focus on defining the nature of functional impairment and decline in patients with PAD, and leading randomized controlled clinical trials to identify optimal exercise programs and novel drug therapies that decrease impairments associated with the disease. She has received a number of prestigious research grants from the Patient-Centered Outcomes Research Institute and the National Heart, Lung, and Blood Institute to support her work. She is board-certified in Internal Medicine and has been a faculty member at Northwestern University Feinberg School of Medicine since 1994. She is an elected member of the American Society of Clinical Investigation and the Association of American Physicians.
About VM202
VM202 is a proprietary gene therapy from VM BioPharma targeting four different indications. When injected into patients, VM202 produces hepatocyte growth factor (HGF) protein, which induces angiogenesis and acts as a neurotrophic factor, leading to the formation of new microvasculature and inducing regeneration of nerve cells. The results from a Phase 2 study in critical limb ischemia showed that the two VM202 treatment groups had statistically significant complete wound closure and wound improvement rates over placebo at the 12-month follow-up (Gene Therapy 2011, 18: 788–794, http://www.nature.com/gt/journal/v23/n3/full/gt2015110a.html). In addition to the HI-PAD study, a Phase 3 trial (NCT02563522) is currently underway to evaluate the efficacy of VM202 for non-healing foot ulcers in patients with diabetes and concomitant PAD.
VM202 also completed a successful Phase 2 study for painful diabetic peripheral neuropathy, (Annals of Clinical and Translational Neurology 2015, Volume 2, Issue 5, 465–478, [http://onlinelibrary.wiley.com/doi/10.1002/acn3.186/abstract;jsessionid=5E9494D0A82AD459C41E3651101DF08F.f02t02), leading to an ongoing Phase 3 study (NCT02427464); and has successfully completed a Phase 1/2 study for amyotrophic lateral sclerosis (ALS) in the United States. A Phase 2 trial is also launching in Korea for the indication of coronary artery disease.
About VM BioPharma and ViroMed Co., Ltd.
VM BioPharma is the US division of ViroMed Co., Ltd., an R&D focused biopharmaceutical company based in Seoul, Korea, developing new and innovative biopharmaceuticals to meet unmet medical needs. Currently, the company is actively focusing on developing the proprietary plasmid DNA-based drug VM202 at various clinical stages in the U.S., Korea, and China, for cardiovascular and neurological diseases.
Media Contact:
Cathy Carroll, PhD, BSPharm
Director-Strategic Business Development
ViroMed Co., Ltd (dba VM BioPharma)
Ph: 1-816-337-9962
E: cathyc@viromed.co.kr
