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.
"In our Phase 1 study, treatment with ISIS-APOCIIIRx produced rapid, dose-dependent median reductions of up to 44 percent in plasma triglycerides and up to 78 percent in apoC-III protein, with two out of the three subjects in the highest dose group achieving undetectable levels of apoC-III. These data underscore the potential therapeutic benefit a selective apoC-III inhibitor could offer patients with elevated levels of triglycerides and apoC-III," said Richard Geary, Ph.D., Senior Vice President of Development at Isis. "Following the encouraging results we observed in our Phase 1 study in healthy volunteers, we hope to achieve similar triglyceride reductions in patients with very high triglycerides in the Phase 2 study we have just initiated. Assuming these data are replicated, we plan to move rapidly into a Phase 3 study in the most severe patients with triglyceride levels greater than 1,000 mg/dL who have been unable to control their triglyceride levels with currently available treatments."
"ISIS-APOCIIIRx represents a significant near-term commercial opportunity for Isis. Our staged development plan for ISIS-APOCIIIRx is designed to allow us to rapidly move to a Phase 3 study designed to bring this important new drug to patients who are underserved with currently available therapies as rapidly as possible," said B. Lynne Parshall, J.D., Chief Operating Officer, Chief Financial Officer and Secretary of Isis. "As we gain additional experience in patients with severe hypertriglyceridemia, we plan to expand our commercial markets to include other less severe patient populations."
Isis Pharmaceuticals, Inc.