Isis Pharmaceuticals Reports Fifth Positive Phase 2 Data Set for ISIS-APOCIII Rx Showing Significant Reductions in Triglyceride and ApoC-III Levels

CARLSBAD, Calif., Nov. 18, 2013 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced new results from its Phase 2 study of ISIS-APOCIII_Rx as a monotherapy in patients with very high to severely high triglycerides.   These new data and an overall summary of the Phase 2 program for ISIS-APOCIII_Rx were presented today by Dr. Rosanne Crooke at the American Heart Association Scientific Sessions in Dallas.  In the Phase 2 study, patients with very high to severely high triglyceride levels were treated with ISIS-APOCIII_Rx as a monotherapy and achieved statistically significant mean reductions of up to 80 percent in apolipoprotein C-III (apoC-III) and up to 71 percent in triglycerides.  In addition, patients treated with ISIS-APOCIII_Rx achieved statistically significant mean increases of up to 46 percent in high-density lipoprotein cholesterol (HDL-C).   These data are consistent with the interim analysis reported in August of this year.   These new data also demonstrated that the favorable changes in lipid parameters were sustained for three months after the last dose.  Isis is hosting a webcast and key opinion leader panel on Tuesday, November 19, 2013 at 07:15 a.m. Central Time. 

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"Patients with extremely high levels of triglycerides are at significant risk of many serious health conditions, including frequent episodes of pancreatitis, which can be life-threatening and require hospitalization.  Although the benefits of lowering triglycerides in these patients are well established, many of these patients are unable to reduce their triglycerides to acceptable levels.  ApoC-III is an important regulator of triglycerides in the blood.  As such, a drug targeted to reduce ApoC-III should have a profound and positive effect on triglyceride levels," said John Kastelein, M.D., Ph.D., professor of medicine, chairman of the department of vascular medicine, Academic Medical Center, University of Amsterdam.  "ISIS-APOCIII_Rx has been shown to be a robust triglyceride-lowering agent in patients with moderately high to severely high triglycerides in multiple Phase 2 settings.  Based on the comprehensive Phase 2 data for ISIS-APOCIII_Rx, I am very encouraged about the therapeutic potential for ISIS-APOCIII_Rx in patients with severely high triglycerides, especially for use in FCS patients who have extremely high triglyceride levels and very limited therapeutic options."

The monotherapy portion of the Phase 2 study of ISIS-APOCIII_Rx is a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of ISIS-APOCIII_Rx in patients with very high to severely high triglyceride levels (between 440 and 2,000 mg/dL).  In this study, patients received 100 mg, 200 mg or 300 mg dose of ISIS-APOCIII_Rx, or placebo via weekly subcutaneous injections for 13 weeks.  Patients treated with 300 mg ISIS-APOCIII_Rx experienced dose-dependent, robust, prolonged and statistically significant mean reductions in apoC-III, triglycerides and apoC-III-associated VLDL particles of 80, 71 and 88 percent from baseline, respectively.  Furthermore, these patients demonstrated a statistically significant mean increase of 46 percent from baseline in HDL-C.  In this study ISIS-APOCIII_Rx was found to be generally safe and well tolerated.  The most common adverse event (AE) was injection site reactions, which were infrequent, predominantly mild and typically resolved rapidly.  There were no flu-like symptoms, no treatment-related elevations of liver enzymes greater than three times upper limit of normal, no abnormalities in renal function and no clinically meaningful changes in other laboratory values.

"We have now demonstrated that ISIS-APOCIII_Rx has the ability to lower triglycerides equally well in patients with high to severely high triglycerides as well as in patients with high triglycerides and type 2 diabetes.  We have demonstrated that ISIS-APOCIII_Rx can work equally well as a single agent and in combination with fibrates to produce significant reductions in apoC-III and triglycerides, and increases in HDL-C.  In addition, the observed positive effect of ISIS-APOCIII_Rx treatment on lipid parameters, improvements in glucose control and trends toward improvements in insulin sensitivity, suggest that ISIS-APOCIII_Rx could have a very attractive therapeutic profile for patients with severely high triglycerides, who often also have diabetes or metabolic syndrome," said Richard Geary, Ph.D., senior vice president of development at Isis. 

ISIS-APOCIII_Rx is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents.  ISIS-APOCIII_Rx targets apoC-III, a protein produced in the liver that plays a central role in the regulation of serum triglycerides.  Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease.  In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates.  Humans with elevated levels of apoC-III have increased dyslipidemia associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome.  In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.  

ABOUT ISIS PHARMACEUTICALS, INC.
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 for the treatment of patients with HoFH.  Isis' patents provide strong and extensive protection for its drugs and technology.  Additional information about Isis is available at www.isispharm.com.

ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
This press release includes forward-looking statements regarding the discovery, development, activity, therapeutic potential and safety of ISIS-APOCIII_Rx.  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, 2012, 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.

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 trademark of Genzyme Corporation.

SOURCE Isis Pharmaceuticals, Inc.