Isis Initiates Phase 1 Clinical Trial of ISIS-APOCIIIRx to Treat Hypertriglyceridemia

Dec 21, 2010, 07:00 ET from Isis Pharmaceuticals, Inc.

CARLSBAD, Calif., Dec. 21, 2010 /PRNewswire/ -- 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."


ISIS-APOCIIIRx targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides.  Recent data suggest that loss-of-function mutations within the apoC-III gene lower triglyceride levels and appear to improve health and extend longevity.  In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates.  In addition, apoC-III mediates insulin resistance, leading to worsening of the metabolic syndrome.  


Isis is exploiting its expertise in RNA to discover and develop novel drugs for its product pipeline and for its partners.  The Company has successfully commercialized the world's first antisense drug and has 22 drugs in development.  Isis' drug development programs are focused on treating cardiovascular, metabolic, and severe neurodegenerative diseases and cancer.  Isis' partners are developing antisense drugs invented by Isis to treat a wide variety of diseases.  Isis and Alnylam Pharmaceuticals are joint owners of Regulus Therapeutics Inc., a company focused on the discovery, development and commercialization of microRNA therapeutics.  Isis also has made significant innovations beyond human therapeutics resulting in products that other companies, including Abbott, are commercializing.  As an innovator in RNA-based drug discovery and development, Isis has designed and executed a patent strategy that has provided the Company with strong and extensive protection for Isis' drugs as well as all aspects of antisense drug discovery, development and manufacturing.  Additional information about Isis is available at


This press release includes forward-looking statements regarding Isis Pharmaceuticals and the discovery and development of ISIS-APOCIIIRx for the treatment of hypertriglyceridemia.  Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs is a forward-looking statement and should be considered an at-risk statement.  Such statements are subject to certain risks and uncertainties, particularly those inherent in the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs.  Isis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to differ materially from those expressed or implied by such forward-looking statements.  Although Isis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Isis.  As a result, you are cautioned not to rely on these forward-looking statements.  These and other risks concerning Isis' programs are described in additional detail in Isis' annual report on Form 10-K for the year ended December 31, 2009 and its most recent quarterly report on Form 10-Q, which are on file with the SEC. Copies of these and other documents are available from the Company.

Isis Pharmaceuticals is a registered trademark of Isis Pharmaceuticals, Inc.  Regulus Therapeutics is a trademark of Regulus Therapeutics Inc.

SOURCE Isis Pharmaceuticals, Inc.