Isis Reports Final Phase 2 Data on ISIS-APOCIII Rx in Patients With High Triglycerides and Type 2 Diabetes

CARLSBAD, Calif., May 1, 2014 /PRNewswire/ -- Isis Pharmaceuticals, Inc. ISIS announced the final results from its Phase 2 study of ISIS-APOCIII_Rx in patients with high triglycerides and type 2 diabetes.  In this study, patients treated with ISIS-APOCIII_Rx achieved statistically significant average mean percent reduction from baseline of 88 percent (p=0.02) in apolipoprotein C-III (apoC-III) and 69 percent (p=0.02) in triglycerides, and an average mean percent increase of 42 percent (p=0.03) in high-density lipoprotein cholesterol (HDL-C) after 13 weeks of dosing.   All treated patients achieved triglyceride levels of less than 104 mg/dL and averaged triglyceride levels under 76 mg/dL by four weeks, and the average triglyceride level was maintained under 76 mg/dL until the end of treatment (a normal triglyceride level is <150 mg/dL).  In addition, patients treated with ISIS-APOCIII_Rx achieved statistically significant reductions in measures of glucose control.  The absolute mean reductions in hemoglobin A1c (HbA1c) were 1.22 percent (placebo-adjusted) and 0.44 percent (from baseline) (p=0.03) after 25 weeks.  In addition to the statistically significant reductions in HbA1c, patients treated with ISIS-APOCIII_Rx achieved statistically significant mean reductions in serum fructosamine of 39 μmol/L (p=0.05) and in glycated albumin of 2 percent (p=0.03) (from baseline) after 13 weeks of dosing.  The effects of ISIS-APOCIII_Rx observed on measures of glucose control were in addition to those achieved with each patient's existing therapeutic regimen of metformin.  Improvements in indicators of insulin sensitivity were also observed in patients suggesting that inhibition of apoC-III could improve insulin sensitivity in patients with high triglycerides and type 2 diabetes. 

"Patients with high levels of triglycerides often have other serious health conditions, including obesity and type 2 diabetes. The significant reductions of both lipid and glucose parameters in patients treated with ISIS-APOCIII_Rx in  this study suggest that reducing apoC-III could have a significant therapeutic impact on patients who, in addition to severely high triglycerides, also have type 2 diabetes," said Joseph L. Witztum, M.D., distinguished professor of medicine at the University of California, San Diego.

The Phase 2 study of ISIS-APOCIII_Rx was a blinded, randomized, placebo-controlled 13-week study designed to assess the safety and activity of 300 mg/week of ISIS-APOCIII_Rx in patients with high triglyceride levels (between 200 and 500 mg/dL) and type 2 diabetes with HbA1c levels between 7.0 percent and 9.0 percent.  The data presented today are a per protocol analysis of the final data (including treatment and follow up period through Day 176).  Isis reported an interim analysis of these data in June 2013.  These new data for ISIS-APOCIII_Rx will be presented today by Dr. Rosanne M. Crooke at the Arteriosclerosis, Thrombosis and Vascular Biology Scientific Sessions in Toronto, Ontario. 

ISIS-APOCIII_Rx was well tolerated in the study with no discontinuations.  The most common adverse event was injection site reactions, which were 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, no clinically meaningful changes in other laboratory values and no treatment-related serious adverse events. 

"We plan to develop ISIS-APOCIII_Rx initially as a therapy for patients with familial chylomicronemia syndrome (FCS), a rare orphan disease in which patients have extremely high triglyceride levels, typically greater than 2,000 mg/dL.  We also plan to develop ISIS-APOCIII_Rx for use in patients with triglyceride levels greater than 880 mg/dL.  Patients with triglyceride levels greater than 880 mg/dL can also have diabetes or metabolic syndrome.  For these patients, a drug that significantly lowers triglyceride and apoC-III levels, significantly reduces HbA1c, and demonstrates improvements in glucose control and insulin sensitivity, could provide unique therapeutic value," said Richard Geary, Ph.D., senior vice president of development at Isis.  "We plan to initiate Phase 3 studies for ISIS-APOCIII_Rx this year." 

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. Humans with elevated levels of apoC-III have high triglycerides 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.   Humans with severely elevated triglycerides are at risk of many serious health conditions, including pancreatitis, which can be life-threatening and require hospitalization.

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 32 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 www.isispharm.com.

ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT

This press release includes forward-looking statements regarding the discovery, development, and potential of drugs for cardiovascular diseases, and the 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, 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.