Background: Bypass graft surgery is one of the most common surgical procedures in the United States. This procedure involves using a section of a patient's vein to bypass clogged arteries that transport blood to the heart or leg by rerouting blood around the clogged artery. There are two types of bypass graft procedures, both of which are performed to improve the flow of blood to the affected organ or limb. Coronary Artery Bypass Graft, or CABG, surgery involves rerouting the flow of blood to the heart, while Peripheral Artery Bypass Graft, or PABG, surgery involves rerouting the flow of blood to the legs. In 2004, 255,609 and 76,774 patients underwent CABG and PABG surgery, respectively, in the United States. One of these patients was former President Bill Clinton, whose quadruple bypass graft surgery raised the public profile of CABG procedures. It remains a common and state of the art therapy, with high press coverage and public awareness.

Problem: While CABG and PABG surgeries are very effective procedures, these grafts often fail due to abnormal cell growth that results in a narrowing of the vein. In all cases of CABG surgery, up to 30% of these grafts fail within the first year with the failure rate increasing to about 50% between years ten and fifteen. The consequences of failure for CABG patients include heart attack, chest pain, congestive heart failure, irregular heartbeat, and death. In the case of PABG surgery, about 20% to 30% of the grafts fail within the first year and up to 50% to 70% fail within five years. The consequences of failure for PABG patients include grave disability and discomfort, poor wound healing, gangrene, amputation of some or all of the limb, and death. Disease in vein grafts in peripheral limbs (most commonly in the lower extremity) and in the heart share the same etiology and treatment options. Grafts used in PABG often fail for the same reasons as those installed during CABG. The surgery to repair a failed or failing graft is a technically difficult procedure with an increased risk of complications.

Lumen Therapeutics' Solution: Lumen's first product candidate to enter clinical development, LT-1951, is intended to prevent vein graft failure following bypass grafting procedures in which autologous saphenous veins are used. LT-1951 will reduce the 20-30% failure rate of CABG vein grafts at the end of one year, and will provide significant support for the potential efficacy of this product candidate for PABG. The Merck Manual of Medical Information-Second Home Edition, Online Version, provides a detailed description of coronary artery disease, peripheral arterial disease, and the bypass procedures:
http://www.merck.com/mmhe/sec03/ch033/ch033b.html#sec03-ch033-ch033b-903 (coronary)
http://www.merck.com/mmhe/sec03/ch034/ch034b.html (peripheral)