Corgentech Inc. said it started enrolling patients in a second Phase III trial for a product likely to set the standard of care in coronary arterial and peripheral bypass grafting surgery.
It should take Corgentech until the end of 2003 to enroll about 2,500 patients in its pivotal Phase III trial designed to evaluate E2F Decoy as a potential treatment for the prevention of graft failure following coronary arterial bypass grafting (CABG) surgery. The company will enroll an additional 500 patients who will be assigned to long-term follow-up care, while the earlier group will be followed for a year.
E2F Decoy, an oligonucleotide or short strand of DNA, is designed to block neointimal hyperplasia and redirect graft biology to strengthen the vessel wall, making it less prone to failure over time.
"We think E2F Decoy could become the standard of care because the procedure takes no additional time during the operation and the surgeon doesn't have to learn anything or do anything different," Richard Powers, chief financial officer of Palo Alto, Calif.-based Corgentech, told BioWorld Today. "The safety profile is very, very good because the procedure is done ex vivo. We've heard from physicians that if it does work, it will become the standard of care and that would be a big product."
Corgentech, a privately held company founded in January 1999, has not partnered, nor does it intend to partner, E2F Decoy. The company raised $50 million a month ago in its Series C financing and expects the money to last through the first or second quarter of 2004. (See BioWorld Today, July 17, 2002.)
The company hopes to file a new drug application for E2F Decoy in late 2004 or early 2005, Powers said. The FDA has granted the product fast-track status.
According to statistics provided by Powers, approximately 400,000 coronary and peripheral bypass grafting surgeries are performed each year in the U.S.
"What we have is a drug that's in a vial, and we inject the drug into the device, then we slide the vein into it and close off the end, and the device puts the drug and vein under pressure for 10 minutes," Powers said. "In that 10 minutes, E2F Decoy is transfected into the nucleus of the cells within the vein. Then the vein is taken out of the device, cleaned and used in the bypass procedure the way it normally is - it looks the same and feels the same - but we've changed the biological pathway that the vein will take when it is finally grafted to the heart."
The second Phase III trial, referred to as PREVENT 4, is a multicenter, placebo-controlled, double-blind, randomized study being coordinated by the Society of Thoracic Surgeons with the Duke Clinical Research Institute at the Duke University Medical Center. The primary efficacy endpoint will be a comparison between the treatment and placebo groups regarding the occurrence of critical graft stenosis, which is defined as 75 percent or greater blockage as measured by angiography.
Meanwhile, Corgentech is continuing to enrolling the earlier, 1,400-patient Phase III trial of E2F Decoy for the prevention of peripheral leg arterial bypass graft failure. It should be completed by the end of next year, the company said.
The company recently released data from a Phase IIb trial showing that a year after surgery, more than 38 percent of grafts in the placebo group experienced failure. In the E2F Decoy treatment group, only 27 percent had graft failure, for a 30 percent relative reduction compared to the placebo group. There was no difference in adverse events in the groups, the company said in a prepared statement.