Isis commences ISIS-APOCIIIRx Phase 1 trial in hypertriglyceridemia

Isis Pharmaceuticals, Inc. (Nasdaq: ISIS) announced the initiation of a Phase 1 study of ISIS-APOCIIIRx, an antisense drug designed to lower triglycerides to treat a variety of diseases associated with elevated triglycerides.  Hypertriglyceridemia, a condition characterized by elevated levels of triglycerides, is an independent risk factor for cardiovascular disease and is a component of numerous cardiovascular and metabolic diseases, including metabolic syndrome.  ISIS-APOCIIIRx inhibits the production of apolipoprotein C-III (apoC-III), a traditionally "undruggable" target that plays a central role in the regulation of triglycerides.

"Humans who cannot produce apoC-III have lower triglycerides and LDL-C levels, increased HDL levels and a lower risk of cardiovascular disease, suggesting that apoC-III inhibition could provide an effective new tool for lipid management.  Many of the current therapies designed to lower triglycerides are associated with undesirable side effects, such as flushing, the most common side effect of niacin," said Rosanne Crooke, Ph.D., Vice President, Cardiovascular Diseases Drug Discovery Research at Isis.  "In preclinical studies, antisense inhibition of apoC-III reduced the target mRNA and protein, lowered triglyceride levels in plasma, mitigated symptoms of metabolic syndrome and decreased atherosclerosis."

"ApoC-III is an excellent antisense target to reduce triglyceride levels and is another example of the broad applicability of our technology to selectively inhibit targets that could have a profound impact on diseases.  ApoC-III inhibits the clearance of triglycerides from the blood.  It is produced in the liver, a tissue that antisense drugs work very effectively in, and it is a target that has been difficult to inhibit with traditional approaches," said Stanley Crooke, M.D., Ph.D., Chairman and Chief Executive Officer of Isis.  "We plan to develop ISIS-APOCIIIRx in a staged program similar to mipomersen, in which we will first evaluate the drug in very sick patients who cannot adequately lower their triglyceride levels using available therapies and who, as a result, have few therapeutic options.  In this regard, we can exploit the knowledge we have gained from our mipomersen and PCSK9 programs to inform our development plan for ISIS-APOCIIIRx."

SOURCE Isis Pharmaceuticals, Inc.