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Press release from Business Wire

Gilead Sciences and Cardiovascular Research Foundation Initiate Phase 3 Clinical Trial with Ranolazine in Patients Who Have Undergone PCI with a History of Prior Chronic Angina

Monday, November 07, 2011

Gilead Sciences and Cardiovascular Research Foundation Initiate Phase 3 Clinical Trial with Ranolazine in Patients Who Have Undergone PCI with a History of Prior Chronic Angina08:30 EST Monday, November 07, 2011 FOSTER CITY, Calif. & NEW YORK (Business Wire) -- Gilead Sciences, Inc. (Nasdaq: GILD) and the Cardiovascular Research Foundation (CRF) today announced the initiation of RIVER-PCI (Ranolazine for Incomplete VEssel Revascularization post-PCI), a Phase 3 clinical trial evaluating the utility of ranolazine to prevent major adverse cardiovascular events (MACE) in patients with a history of chronic angina who have incomplete revascularization following percutaneous coronary intervention (PCI). RIVER-PCI will enroll 2,600 patients at approximately 200 investigative centers in the United States, Canada, Europe and Israel. PCI is a common procedure used to revascularize (unblock) narrowed coronary arteries and improve blood flow to the heart. Incomplete revascularization is defined as having residual disease (50 percent or greater stenosis or narrowing) following the PCI in one or more coronary arteries. “Despite the widespread use of revascularization technologies and optimal medical therapy for coronary artery disease, the incidence of angina after PCI remains high, contributing to repeat procedures and hospitalizations, as well as increased outpatient testing and resource utilization,” said Gregg W. Stone, MD, Professor of Medicine and Director of Cardiovascular Research and Education at Columbia University Medical Center (CUMC) and Co-Director of the Medical Research and Education Division at CRF. “In analyses of registries and clinical trial data, recurrent anginal or ischemic symptoms after PCI have been found to be more common in patients with incomplete revascularization, suggesting that new therapeutic strategies are needed.” “Ranolazine has established safety and efficacy as treatment for chronic stable angina, but this is the first time the therapy is being studied specifically in a post-PCI setting as part of a randomized clinical trial,” said Norbert W. Bischofberger, PhD, Gilead's Executive Vice President, Research and Development and Chief Scientific Officer. “We are pleased to partner with CRF on this study, which will determine if the addition of ranolazine to standard therapy is effective in reducing post-PCI ischemic events, including reductions in post-PCI hospitalization, repeat PCI and the incidence of myocardial infarction and death.” RIVER-PCI will be led by principal study investigator Giora Weisz, MD, Director of Cardiovascular Research at CUMC and chaired by Dr. Stone. Ranolazine is indicated for the treatment of chronic angina. Ranolazine has not been determined to be safe or efficacious as a treatment to reduce major adverse cardiovascular events in patients who have undergone PCI. Study Design RIVER-PCI is a randomized, double-blind, placebo-controlled study designed to evaluate the effects of ranolazine on major adverse cardiovascular events (MACE) in patients with a history of chronic angina who undergo PCI with incomplete revascularization. The study will enroll 2,600 patients with a history of chronic angina who undergo coronary angiography and PCI either for an acute coronary syndrome (ACS) or for an elective (non-ACS) indication and who have angiographic evidence of incomplete revascularization following the procedure. Eligible post-PCI patients will be randomized in a 1:1 ratio to receive twice-daily ranolazine or matching placebo in addition to their standard medical therapy and followed for at least one year post randomization. The study will continue until at least 721 post-randomization major adverse cardiovascular events have been observed. The primary efficacy endpoint is the incidence of MACE, as defined by the composite of cardiovascular death, myocardial infarction (MI) or hospitalization for ischemia or angina. Secondary endpoints include the incidence of the individual components of the primary endpoint, sudden cardiac death and evaluation of quality of life and health-related costs. About Ranolazine Ranolazine is an extended-release tablet approved under the tradename Ranexa® as a treatment for chronic angina. Ranexa may be used in combination with beta blockers, nitrates, calcium channel blockers, anti-platelet therapy, lipid-lowering therapy, ACE inhibitors and angiotensin receptor blockers. Ranexa was approved in the United States in January 2006. In 2008, the U.S. Ranexa indication was updated to include first-line treatment for chronic angina. Ranexa at therapeutic levels can inhibit the cardiac late sodium current. However, the mechanism of Ranexa's antianginal effects has not been established. The relationship between the inhibition of the late sodium current and angina symptoms is uncertain. A large placebo-controlled trial of Ranexa in patients with acute coronary syndrome did not achieve the primary efficacy endpoint for Ranexa of a reduction in the composite of cardiovascular death, myocardial infarction or recurrent ischemia. Ranexa is not approved for the treatment of acute coronary syndrome. Important Safety Information Ranexa is contraindicated in patients taking strong inhibitors of CYP3A (e.g., ketoconazole itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir and saquinavir), in patients taking inducers of CYP3A (e.g., rifampin, rifabutin, rifapentin, phenobarbital, phenytoin, carbamazepine and St. John's wort) and in patients with liver cirrhosis. Ranexa blocks IKr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of proarrhythmia or sudden death. However, there is little experience with high doses (> 1000 mg twice daily) or exposure, other QT-prolonging drugs, potassium channel variants resulting in a long QT interval, in patients with a family history of (or congenital) long QT syndrome, or in patients with known acquired QT interval prolongation. The most common adverse reactions (greater than 4 percent and more common than placebo) during treatment with Ranexa were dizziness, headache, constipation and nausea. It is recommended to initiate Ranexa treatment with 500 mg twice daily and increase to the maximum recommended dose of 1000 mg twice daily, based on clinical symptoms. Ranexa tablets should be swallowed whole; do not crush, break or chew. The maximum dose of Ranexa should be limited to 500 mg twice daily in patients on moderate CYP3A inhibitors (e.g., diltiazem, verapamil, erythromycin, fluconazole and grapefruit juice or grapefruit-containing products). Ranexa should not be used with CYP3A inducers or strong CYP3A inhibitors. The dose of Ranexa should be modified with moderate CYP3A inhibitors. Ranexa exposure is increased with P-gp inhibitors (e.g., cyclosporine); titrate Ranexa based on clinical response. Limit simvastatin to 20 mg when used with Ranexa. Doses of other sensitive CYP3A substrates (e.g., lovastatin) and CYP3A substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with Ranexa. Doses of drugs transported by P-gp (e.g., digoxin) or metabolized by CYP2D6 (e.g., tricyclic antidepressants and antipsychotics) may need to be reduced. Full prescribing information for Ranexa is available at www.gilead.com and at www.ranexa.com. About Cardiovascular Research Foundation The Cardiovascular Research Foundation (CRF) is an independent, academically focused nonprofit organization dedicated to improving the survival and quality of life for people with cardiovascular disease through research and education. Since its inception in 1991, CRF has played a major role in realizing dramatic improvements in the lives of countless numbers of patients by establishing the safe use of new technologies, drugs and therapies in the subspecialty of interventional cardiology and endovascular medicine. For more information, please visit www.crf.org. About Gilead Sciences Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific. For more information on Gilead, please visit www.gilead.com. Gilead Forward-Looking Statement This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risks related to Gilead's ability to enroll patients in the Phase 3 clinical trial as planned, the possibility of unfavorable results of the clinical trial, the need to modify or delay our clinical trial or to perform additional trials and the risk of failing to obtain approvals from regulatory authorities. As a result, use of ranolazine to reduce major adverse cardiovascular events in post-PCI patients with a history of prior chronic angina may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of ranolazine in post-PCI patients with a history of prior chronic angina if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended June 30, 2011, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements. Ranexa is a registered trademark of Gilead Sciences, Inc.Gilead Contacts:InvestorsPatrick O?Brien, 650-522-1936MediaNathan Kaiser, 650-522-1853orCRF Contact:Judy Romero, 516-557-6557