Isis Pharmaceuticals Initiates Phase 1 Study of ISIS-ANGPTL3 Rx to Treat Hyperlipidemia

Mar 19, 2014, 07:00 ET from Isis Pharmaceuticals, Inc.

CARLSBAD, Calif., March 19, 2014 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced today that it has initiated a Phase 1 clinical study for ISIS-ANGPTL3Rx, an antisense drug targeting angiopoietin-like 3 protein (ANGPTL3), an independent risk factor for cardiovascular disease. ISIS-ANGPTL3Rx is designed to act as a broad dyslipidemia agent.  By reducing ANGPTL3, ISIS-ANGPTL3Rx has the potential to reduce LDL-cholesterol and triglycerides, and to increase insulin sensitivity.  Isis plans to evaluate ISIS-ANGPTL3Rx in patients who have severe metabolic or cardiovascular disease and who would benefit from a drug that simultaneously addresses a variety of adverse lipid and metabolic parameters contributing to their disease.

"ANGPTL3 is a genetically validated target.  We know that humans who have loss-of-function mutations in ANGPTL3 exhibit lower levels of LDL-cholesterol and triglycerides and also display increased insulin sensitivity," said Sotirios Tsimikas, M.D., Professor of Medicine, Director of Vascular Medicine, University of California, San Diego.  "Patients with dyslipidemia often have multiple cardiovascular and metabolic risk factors.  As such, treating these patients can be challenging and involve multiple different treatment regimens.  These patients would benefit tremendously from a drug that could provide benefit across multiple cardiovascular risk factors, like LDL-cholesterol and triglycerides, which are often too high despite currently available drugs."  

"In preclinical studies, we observed significant reductions of LDL-cholesterol and triglycerides associated with reductions in ANGPTL3.  We also observed reduced atherosclerosis in a mouse model of atherosclerosis," said Walter Singleton, M.D., vice president of development and chief medical officer at Isis.  "We are developing ISIS-ANGPTL3Rx as a broad dyslipidemia agent.  Based on our preclinical data, we believe that reducing ANGPTL3 could have a beneficial impact on many lipid parameters, including LDL-cholesterol, triglycerides, total-cholesterol as well as effects on insulin sensitivity and other metabolic parameters."

The Phase 1 study of ISIS-ANGPTL3Rx is a blinded, placebo-controlled, dose-escalation study in approximately 48 healthy volunteers.  The study is designed to assess the safety, tolerability and pharmacokinetics of both single and multiple doses of ISIS-ANGTPL3Rx.


Isis is exploiting its leadership position in antisense technology to discover and develop novel drugs for its product pipeline and for its partners.  Isis' broad pipeline consists of 31 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, including neurological disorders, and cancer.  Isis' partner, Genzyme, is commercializing Isis' lead product, KYNAMRO®, in the United States and other countries for the treatment of patients with homozygous FH.  Isis' patents provide strong and extensive protection for its drugs and technology.  Additional information about Isis is available at


This press release includes forward-looking statements regarding the discovery, development, activity, therapeutic potential and safety of ISIS-ANGPTL3Rx and the therapeutic potential of discovering a drug that reduces the production of ANGPTL3 protein.  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, 2013, which is on file with the SEC. Copies of this and other documents are available from the Company.

In this press release, unless the context requires otherwise, "Isis," "Company," "we," "our," and "us" refers to Isis Pharmaceuticals and its subsidiaries.

Isis Pharmaceuticals® is a registered trademark of Isis Pharmaceuticals, Inc.  KYNAMRO® is a registered trademark of Genzyme Corporation.

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SOURCE Isis Pharmaceuticals, Inc.