Isis Initiates Phase 2 Study of ISIS-APOCIIIRx in Patients with Hypertriglyceridemia

CARLSBAD, Calif., May 4, 2012 /PRNewswire/ -- Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) announced the initiation of a Phase 2 study evaluating ISIS-APOCIIIRx in patients with hypertriglyceridemia.  Hypertriglyceridemia, a condition characterized by high levels of triglycerides, is often associated with premature coronary artery disease and pancreatitis.   Patients with severe hypertriglyceridemia often cannot control their triglyceride levels with existing medicines.  ISIS-APOCIIIRx lowers triglycerides by reducing the protein, apoC-III.  Both triglycerides and apoC-III are independent risk factors for cardiovascular disease.  Isis is pursuing a staged development plan for ISIS-APOCIIIRx designed to shorten the time to bring this medicine to patients at high-risk of cardiovascular disease and pancreatitis.  ISIS-APOCIIIRx is the third drug to advance into Phase 2 clinical studies from Isis' cardiovascular franchise.  In this franchise, Isis is creating a suite of drugs targeting each of the atherogenic lipid components of cardiovascular disease to allow lipidologists to tailor treatment for the particular combination of lipid disorders that affect each individual patient.   

"Patients with high levels of triglycerides are at a significant risk of cardiovascular disease and stroke. Also patients with severely elevated triglycerides are at risk of pancreatitis.  In many patients with very high triglycerides current treatments cannot reduce their triglycerides to safe levels.  There is a significant need for a treatment for these patients that can further lower their triglycerides and reduce their cardiovascular and other health risks," said Joseph L. Witztum, M.D., Professor of Medicine, University of California, San Diego.  "ApoC-III plays an important role in triglyceride metabolism and is also an independent cardiovascular risk factor.  Reducing both apoC-III and triglyceride levels could provide significant therapeutic benefits.  For example, a drug that lowers triglycerides in patients with severe hypertriglyceridemia would undoubtedly reduce their immediate risk of pancreatitis and in the long-term, might also reduce their risk of cardiovascular disease.  Furthermore, in patients with type 2 diabetes, reducing apoC-III and triglycerides may lead to improved insulin sensitivity and improvement of metabolic syndrome, both of which would be highly desirable."

The Phase 2 study is a randomized, placebo-controlled, dose-response study evaluating the safety and efficacy of ISIS-APOCIIIRx in patients with very high triglycerides.  The three-month study will enroll approximately 100 patients who have triglyceride levels of 500 mg/dL or higher.  The study will evaluate ISIS-APOCIIIRx as a monotherapy and in combination with fibrates in patients.  The endpoints for the study include measurements of triglycerides both before and after eating and apoC-III levels in blood. 

"In our Phase 1 study, treatment with ISIS-APOCIIIRx produced rapid, dose-dependent median reductions of up to 44 percent in plasma triglycerides and up to 78 percent in apoC-III protein, with two out of the three subjects in the highest dose group achieving undetectable levels of apoC-III.  These data underscore the potential therapeutic benefit a selective apoC-III inhibitor could offer patients with elevated levels of triglycerides and apoC-III," said Richard Geary, Ph.D., Senior Vice President of Development at Isis. "Following the encouraging results we observed in our Phase 1 study in healthy volunteers, we hope to achieve similar triglyceride reductions in patients with very high triglycerides in the Phase 2 study we have just initiated.  Assuming these data are replicated, we plan to move rapidly into a Phase 3 study in the most severe patients with triglyceride levels greater than 1,000 mg/dL who have been unable to control their triglyceride levels with currently available treatments."

"ISIS-APOCIIIRx represents a significant near-term commercial opportunity for Isis.  Our staged development plan for ISIS-APOCIIIRx is designed to allow us to rapidly move to a Phase 3 study designed to bring this important new drug to patients who are underserved with currently available therapies as rapidly as possible," said B. Lynne Parshall, J.D., Chief Operating Officer, Chief Financial Officer and Secretary of Isis.  "As we gain additional experience in patients with severe hypertriglyceridemia, we plan to expand our commercial markets to include other less severe patient populations."

Conference Call and Webcast Slide Presentation

At 11:00 a.m. EDT today, May 4, 2012, Isis will conduct a live webcast and slide presentation conference call to discuss the clinical development plans for ISIS-APOCIIIRx.  Interested parties may listen to the call by dialing 866-831-6272 and refer to passcode "ISIS 2012" or access the webcast with or without audio at www.isispharm.com.  A webcast replay will be available for a limited time at the same address.

ABOUT ISIS-APOCIIIRx

ISIS-APOCIIIRx inhibits the production of apolipoprotein C-III, or apoC-III, a traditionally 'undruggable' target that inhibits the clearance of triglycerides from the blood.  ApoC-III is responsible for triglyceride transport in the blood and is an independent cardiovascular risk factor. People who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. ApoC-III is elevated in patients with dyslipidemia, or an abnormal concentration of lipids in the blood, and is frequently associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In human population studies, lower levels of apoC-III and triglycerides correlated with a lower rate of cardiovascular events. In certain populations, apoC-III mediates insulin resistance, which can make metabolic syndrome worse. 

ABOUT HYPERTRIGLYCERIDEMIA

Hypertriglyceridemia can be caused by genetic defects, diet, obesity and uncontrolled diabetes and can lead to serious health problems, including cardiovascular disease and pancreatitis.  Triglycerides are an important measure of heart health and are routinely measured along with LDL-cholesterol and HDL-cholesterol.  Triglyceride levels of less than 150 mg/dL are considered within a normal range, and the American Heart Association recommends that a triglyceride level of less than 100 mg/dL is optimal.  Triglyceride levels of greater than 500 mg/dL are considered very high and levels greater than 1,000 mg/dL are considered to be severely high.  In these patients, diet and exercise have limited therapeutic benefit.  Patients with severely high triglycerides are at a higher risk of developing pancreatitis, a painful and sometimes fatal disease that requires hospitalization and close monitoring.  Based on prevalence data, Isis estimates there are greater than 200,000 patients with severely high triglycerides in the United States and Europe despite currently available therapies.

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 26 drugs to treat a wide variety of diseases with an emphasis on cardiovascular, metabolic, severe and rare diseases, and cancer.  Isis' partner, Genzyme, plans to commercialize Isis' lead product, KYNAMRO™, following regulatory approval, which is expected in 2012.  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 for drugs for cardiovascular diseases, and the development activities, therapeutic and commercial potential and safety of ISIS-APOCIIIRx.  Any statement describing Isis' goals, expectations, financial or other projections, intentions or beliefs, including the planned commercialization of KYNAMRO, 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, 2011, 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, including Regulus Therapeutics Inc., its jointly owned subsidiary.

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

SOURCE Isis Pharmaceuticals, Inc.