Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced the initiation of a Phase 2 study evaluating ISIS-APOCIIIRx in patients with hypertriglyceridemia. Hypertriglyceridemia, a condition characterized by high levels of triglycerides, is often associated with premature coronary artery disease and pancreatitis. Patients with severe hypertriglyceridemia often cannot control their triglyceride levels with existing medicines. ISIS-APOCIIIRx lowers triglycerides by reducing the protein, apoC-III. Both triglycerides and apoC-III are independent risk factors for cardiovascular disease. Isis is pursuing a staged development plan for ISIS-APOCIIIRx designed to shorten the time to bring this medicine to patients at high-risk of cardiovascular disease and pancreatitis. ISIS-APOCIIIRx is the third drug to advance into Phase 2 clinical studies from Isis' cardiovascular franchise. In this franchise, Isis is creating a suite of drugs targeting each of the atherogenic lipid components of cardiovascular disease to allow lipidologists to tailor treatment for the particular combination of lipid disorders that affect each individual patient.
"Patients with high levels of triglycerides are at a significant risk of cardiovascular disease and stroke. Also patients with severely elevated triglycerides are at risk of pancreatitis. In many patients with very high triglycerides current treatments cannot reduce their triglycerides to safe levels. There is a significant need for a treatment for these patients that can further lower their triglycerides and reduce their cardiovascular and other health risks," said Joseph L. Witztum, M.D., Professor of Medicine, University of California, San Diego. "ApoC-III plays an important role in triglyceride metabolism and is also an independent cardiovascular risk factor. Reducing both apoC-III and triglyceride levels could provide significant therapeutic benefits. For example, a drug that lowers triglycerides in patients with severe hypertriglyceridemia would undoubtedly reduce their immediate risk of pancreatitis and in the long-term, might also reduce their risk of cardiovascular disease. Furthermore, in patients with type 2 diabetes, reducing apoC-III and triglycerides may lead to improved insulin sensitivity and improvement of metabolic syndrome, both of which would be highly desirable."
The Phase 2 study is a randomized, placebo-controlled, dose-response study evaluating the safety and efficacy of ISIS-APOCIIIRx in patients with very high triglycerides. The three-month study will enroll approximately 100 patients who have triglyceride levels of 500 mg/dL or higher. The study will evaluate ISIS-APOCIIIRx as a monotherapy and in combination with fibrates in patients. The endpoints for the study include measurements of triglycerides both before and after eating and apoC-III levels in blood.