Lumen Therapeutics Begins Phase I/IIA Trial Of LT-1951 For Prevention Of Coronary Artery Bypass Graft (CABG) Failure

2005-03-22

MOUNTAIN VIEW, Calif., March 22 /PRNewswire/ -- Lumen Therapeutics, LLC today announced that the first patients have been enrolled in the Company's Phase I/IIA clinical trial evaluating its lead product, LT-1951, as a treatment for the prevention of graft failure following saphenous vein coronary artery bypass graft (CABG) surgery. LT-1951, used to treat the excised saphenous vein before grafting, naturally penetrates into the vein, suppresses neointimal hyperplasia [the first step in saphenous vein graft disease (SVGD)], and allows the grafts to develop strengthened walls -- making them less prone to failure over time. "All preclinical testing indicated that LT-1951 is an exceptionally safe and effective treatment, and we are hopeful that data from this trial will support our initial findings," commented Paul McGrane, Ph.D., Lumen Therapeutics' Vice-President of Biopharmaceutical Development. "We are working closely with MDs at the forefront of cardiovascular surgery and imaging and have designed an innovative trial that has the potential to demonstrate the safety and efficacy of this novel therapy." The Lumen sponsored PATENT trial is a placebo-controlled, double-blinded, and randomized Phase I/IIA study being performed at Toronto General Hospital (TGH). TGH is home to the largest open-heart surgery center in Canada and has the best clinical outcomes of cardiovascular surgery in the country. Under the direction of Dr. Stephanie Brister, Principle Investigator for the PATENT trial, 50 patients requiring multiple-vein CABG will undergo comparative treatment of LT-1951 and placebo. Each patient will receive at least one graft treated with LT-1951 and at least one graft treated with placebo. The primary biological endpoint will be the within-patient difference in lumen loss for the treated versus placebo grafts, as assessed by Intravascular Ultrasound at 12 months. "We are extremely pleased to be working with TGH on this study. This site can rapidly recruit the patients we need for our study, and their expertise will assure that the trial is of the highest quality," said Dr. Robert Robbins, Chair of the Department of Cardiothoracic Surgery at Stanford School of Medicine and Scientific Advisor to Lumen Therapeutics, a member of a team that includes Nobel laureate, Dr. Ferid Murad. About Coronary Artery Bypass Graft Failure CABG is a common surgical procedure in which a section of a patient's vein is used to bypass clogged arteries that transport blood to the heart. In 2000, approximately 40,000 patients in Canada and 375,000 in the U.S. underwent CABG. Former-President Clinton's recent CABG surgery did much to promote public understanding of the procedure. While CABG surgery is a very effective procedure, the grafts often fail due to saphenous vein graft disease (SVGD), a narrowing of the vein's internal diameter (lumen) characterized by neointimal hyperplasia and subsequent formation of atherosclerotic plaque. In the first year after bypass surgery, up to 15% of vein grafts will occlude and most grafts will exhibit some SVGD. The consequences of failure can include heart attacks, chest pain, congestive heart failure, irregular heartbeat, and death. The additional surgery required to repair a failed or failing graft is technically difficult and carries an increased risk of complications. There is no currently approved therapeutic for the prevention of SVGD following CABG. About LT-1951 LT-1951 is an aqueous solution of a short peptide comprised of repeating units (a polymer) of a natural amino acid, L-arginine. The drug efficiently penetrates into vascular tissues like the saphenous vein and supplies the tissue with a sustained reservoir of L-arginine, the substrate for production of nitric oxide. Nitric oxide (NO) is an important vasoactive and cell signaling compound implicated in suppression of neointimal hyperplasia. NO limits neointimal hyperplasia by inhibiting monocyte chemotaxis and adherence, platelet adherence and aggregation, and vascular smooth muscle cell proliferation. A dramatic reduction of neointimal hyperplasia following treatment with LT-1951 has been demonstrated in preclinical vein to artery interposition studies in several animal models. Marked improvement following a single ex vivo application of LT-1951 in interposition grafts demonstrated that the beneficial effect of the drug is not dependent upon continued treatment of the grafted tissue. In the PATENT trial, saphenous vein grafts are harvested in the usual manner from the patient's leg and are bathed in LT-1951 or placebo ex vivo (at normal pressure and temperature) before being rinsed and implanted into the patient. Because LT-1951 is applied only to the graft, there is minimal systemic exposure and risk to the patient. About Lumen Therapeutics Lumen Therapeutics is a biopharmaceutical company focused on the development and commercialization of proprietary biopharmaceuticals based on polymers of L-arginine. Lumen is researching a pipeline of novel therapeutics based on this proprietary technology. Lumen Therapeutics, LLC CONTACT: Paul McGrane, Ph.D., of Lumen Therapeutics, LLC,+1-650-641-0084, or business_development@lumentherapeutics.com Web site:

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