By Randall Osborne
Cypros Pharmaceuticals Corp. said it plans to begin Phase III trials early next year of CPC-111, the company's "metabolic enhancer" drug given intravenously to lessen heart damage during coronary artery bypass grafting and help patients resume heart function after the surgery.
CPC-111, described as a naturally occurring intermediate of energy metabolism, works by generating energy for the heart after ischemia, which is the blockage of blood flow that makes cardiovascular episodes such as heart attacks so deadly. Ischemia is the number one cause of death in the U.S and most developed countries. CPC-111 blocks ischemia's effect by maintaining the cell process of glycolysis, or conversion of glucose to stored energy. As lactic acid builds up following an ischemic event, glycolysis typically stops.
Cypros, of Carlsbad, Calif., chose coronary artery grafting as the focus of its Phase III trials after evaluating CPC-111 in angioplasty, congestive heart failure and bypass graft surgery, said Paul Marangos, president, chairman and CEO. "Bypass surgery is really frank, extreme ischemia," he said. "You're stopping the heart for up to two hours."
The Phase III trials will use 400 to 600 patients, and at least 30 sites, Marangos said. Other details of protocol have not been established, although Marangos has affirmed a number of endpoints.
One endpoint is heart damage, as measured by the creatine kinase muscle band (CKMB) test. "You want to show that, if you pre-treat, you get less damage to the heart post-surgery," Marangos said.
Another endpoint is heart function, as measured by hemodynamic tests such as the cardiac index, showing how much blood is being pumped; the left ventricular stroke work index, gauging how much force the heart's left ventricle generates when it contracts; and the pulmonary wedge pressure index, determining how much "back" pressure is exerted against the heart while it pumps.
A third endpoint is "pharmacoeconomic," Marangos said. "How long does the patient stay in the hospital? How long in intensive care?" Phase II trial results showed patients' intensive-care time dropped by 50 percent, he said.
The endpoints will be narrowed down before the trials begin, and are likely to focus on CKMB measures and length of hospital stays, Marangos said. "Which will be the primary and which will be the secondary, we haven't decided," he said.
Cypros announced earlier that Phase III trials also will begin next year for Ceresine, or CPC-211, which also protects cells from ischemic damage but is used in closed head injuries to safeguard the brain. CPC-211 "works by a totally different mechanism," reducing lactic acid buildup so the damaging reactions that are helped by CPC-111 do not occur in the first place, Marangos said.
The company has three products already on the market. Glofil and Inuline are used to measure kidney function. Ethamolin stops bleeding during surgery. Cypros reported sales of $2.428 million for its fiscal year ending July 31, up 90 percent over the previous year.
Marangos said Cypros' net loss was $6.674 million, and the company had $14.6 million in cash and equivalents at the end of the fiscal year. Losses are expected to rise to about $6 million next year, he said. The company's stock (NASDAQ:CYPR) closed Thursday at $4.25, up $0.188. *