By Lisa Seachrist
WASHINGTON — Cypros Pharmaceuticals Corp. has begun recruiting clinical sites for a pivotal Phase III clinical trial to begin in August of Cordox (CPC-111) for the treatment of painful episodes of sickle cell anemia crisis.
The study marks the Carlsbad, Calif.-based company's first Phase III study of its lead product, Cordox, a naturally occurring intermediate of energy metabolism that helps red blood cells maintain their normal shape and improves overall blood flow
"This is the first real metabolic approach to sickle cell disease," said Chairman and CEO Paul Marangos. "We are moving away from palliative approaches to the underlying biology."
Sickle cell disease is the most prevalent genetic disorder worldwide. Approximately 80,000 people in the U.S. have full manifestation of the disease. In sickle cell disease, blood cells are prone to deforming as a result of the polymerization of hemoglobin. The deformed blood cells clog blood vessels and starve tissues of oxygen, causing the severe pain that hallmarks a vaso-occlusive episode (VOE). Over a patient's lifetime, tissue damage accumulates with each new episode.
Current treatments for VOE includes opioid analgesics, hydration, antibiotics and blood transfusions.
Cordox, as an intermediate of anaerobic energy production, works by supplying energy in the form of adenosine triphosphate to sickled red blood cells, allowing them to become more pliable by depolymerizing hemoglobin and improving overall blood flow. In addition, Cordox provides energy to oxygen-starved tissues, preventing damage to those tissues as well as preventing damage to blood vessel walls.
Phase II studies of Cordox showed that patients suffering VOE found considerable relief from the pain of the episode, prompting the company to move to Phase III studies. The pivotal trial will include 280 patients and be a double-blind, placebo-controlled study conducted at approximately 30 medical centers.
Cypros intends to measure the level of pain reduction, use of opiates, length of the episode and length of hospital stay. Marangos pointed out that patients typically spend a week in the hospital as a result of VOE. Taking a day off that stay will not only improve patients' quality of life but will provide significant health care savings.
"The protective effect of Cordox on ischemic tissue combined with its ability to reduce red blood cell sickling and improve overall blood flow means we are treating the cause of VOE," Marangos said. "We are very excited by this possibility."
Cypros announced in October 1997 that it was prepared to test Cordox as a treatment for ischemia during bypass surgery to help patients regain heart function following surgery.
However, Marangos told BioWorld Today that the Phase II results from Cordox in sickle cell were so promising that the company decided to move forward with that indication first. In addition, Marangos said that it would take a much smaller clinical trial to prove efficacy in sickle cell disease. Cypros will attempt to find subgroups of patients to test the heart surgery indication in order to have a manageably sized trial.
The company has three products already on the market. Glofil and Inuline are used to measure kidney function. Ethamolin stops bleeding during surgery. The company's stock (AMEX:CYP) closed at $4.25 unchanged. *