Amgen presents analyses of Phase 3 Ivabradine data for the treatment of chronic heart failure

THOUSAND OAKS, Calif., Sept. 14, 2014 -- Amgen (NASDAQ:AMGN) today announced data from the Phase 3 SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) study evaluating ivabradine in patients with chronic heart failure (HF) were presented at the 18th Annual Scientific Meeting of the Heart Failure Society of America (HFSA) in Las Vegas. A post-hoc analysis from the SHIFT study confirmed low systolic blood pressure (SBP) is associated with poor outcomes in chronic HF, and that ivabradine reduced the primary composite endpoint of cardiovascular death or hospitalization for worsening HF in this subgroup with low baseline SBP. Safety was similar across the three SBP groups. Results were published in the July 2014 issue of the European Journal of Heart Failure.1

Ivabradine is an oral drug that inhibits the If current ("funny" current) in the sinoatrial node, the body's cardiac pacemaker.2 It works to slow the heart rate without negative effects on myocardial contractility or ventricular repolarization.2  

"Despite standard of care, chronic heart failure remains a disabling condition with a poor prognosis for patients at risk for hospitalization," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Analyses from the pivotal SHIFT study complement the main trial findings that form the basis of our U.S. submission package for ivabradine. We recently received a priority review designation for ivabradine from the FDA and are working with the agency to potentially bring this important treatment option to certain patients with chronic heart failure in the U.S. as soon as possible."

In August 2014, the U.S. Food and Drug Administration (FDA) granted ivabradine priority review designation, which is assigned to applications for drugs that treat serious conditions and would, if approved, provide significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions compared to available therapies.3 FDA will target a priority review Prescription Drug User Fee Act (PDUFA) action date of Feb. 27, 2015.

The SHIFT study is a large, multi-center, randomized, double-blind, placebo-controlled, outcomes trial that compared ivabradine to placebo on top of standard-of-care therapies, including beta-blockers, in more than 6,500 patients with symptomatic chronic HF in sinus rhythm with reduced left ventricular function and heart rate >70 beats per minute (bpm).

At HFSA, Amgen presented a post-hoc analysis of the SHIFT study that evaluated the efficacy and safety of ivabradine across three different blood pressure groups, divided according to SBP: low SBP (<115 mm Hg; n=2,010), intermediate SBP (115-130 mm Hg; n=1,968) and high SBP (>130 mm Hg; n=2,427). The analysis confirmed chronic HF with low SBP is associated with poor outcomes, and that ivabradine reduced the primary composite endpoint of cardiovascular death and hospitalization for worsening HF independent of baseline SBP. Safety was similar across the three SBP groups. The most common adverse events were phosphenes and bradycardia, which occurred more frequently with ivabradine.

"Low blood pressure is a common condition in chronic heart failure that complicates management and is associated with negative outcomes such as death and hospitalization," said Jeffrey S. Borer, M.D., professor of medicine, cell biology, radiology and surgery, State University of New York, Downstate Medical Center. "The analysis from the SHIFT study showed consistent results regardless of systolic blood pressure, which provides further evidence that ivabradine has the potential to improve clinical outcomes, on top of standard therapy, in certain patients with chronic heart failure."

Additional findings presented at the HFSA meeting included data from a pre-specified Holter electrocardiography sub-study (ECG-Holter sub-study), which evaluated 501 patients from the SHIFT trial to better understand the relationship between heart rate and safety/incidence of adverse events while taking ivabradine on top of optimized HF therapy, including beta blockers. Results showed that at eight months, 24-hour heart rate was significantly reduced by 9.5 + 10.1 bpm in the ivabradine group (n=254) versus 1.2 + 8.9 bpm in the placebo group (n=247)  (p<0.0001). Higher rates of at least one episode of heart rate less than 40 bpm were also reported in the ivabradine group (p<0.0001). No increase in significant pauses, second/high degree atrioventricular block or arrhythmias was observed in the ivabradine group in this sub-study.

Heart failure is a common condition that affects approximately 26 million worldwide, including approximately 5.1 million people in the U.S.4,5 It is the leading cause of rehospitalization in Medicarebeneficiaries over age 55,6 and approximately 50 percent of people diagnosed with HF in the U.S. die within five years of diagnosis.5 Projections show that by 2030, the prevalence of HF will increase 25 percent from 2013 estimates.5 Despite broad use of standard treatments, the prognosis for HF is poor.7

SHIFT Study Design
SHIFT (Systolic Heart failure treatment with the If inhibitor ivabradine Trial) is a large, multi-center, randomized, double-blind, placebo-controlled, outcomes study involving more than 6,500 patients in 37 countries. The Phase 3 SHIFT study compared  ivabradine to placebo on top of standard-of-care therapies (including beta blockers, angiotensin converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARB), diuretics and/or aldosterone antagonists), in patients with symptomatic chronic HF in sinus rhythm with reduced left ventricular function and heart rate >70 bpm. After a run-in period of 14 days without study treatment, eligible patients were randomized to receive ivabradine or placebo, with a starting dose of 5 mg daily. After a 14-day titration period, at Day 14, the dose was increased to 7.5 mg twice daily, unless the resting heart rate was 60 bpm or lower. If resting heart rate fell below 50 bpm or patients experienced signs or symptoms of bradycardia, the dose was reduced to 2.5 mg twice daily. The double-blind treatment period lasted approximately 12-48 months.     

The primary endpoint was the composite of cardiovascular death or hospitalization for worsening HF. The first secondary endpoint was the composite of cardiovascular death or hospitalization for worsening HF in patients receiving at least 50 percent of the target daily dose of beta blockers at randomization. Other secondary endpoints included all-cause death, any cardiovascular death, hospitalization for worsening HF, all-cause hospitalization, any cardiovascular hospitalization and death from HF, and the composite of cardiovascular death, hospitalization for worsening HF or hospitalization for non-fatal myocardial infarction.

The SHIFT study, which completed in May 2010, was funded by Les Laboratoires Servier and coordinated by the SHIFT executive committee, an international group of HF experts.

About Ivabradine
Ivabradine is an investigational oral drug that inhibits the If current ("funny" current) in the sinoatrial node, the body's cardiac pacemaker.1 Ivabradine works to slow the heart rate without negative effects on myocardial contractility or ventricular repolarization.1 Developed by Les Laboratoires Servier, ivabradine was approved by the European Medicines Agency (EMA) as PROCORALAN® in 2005 for the symptomatic treatment of stable angina and in 2012 for chronic heart failure (HF) in patients with elevated heart rates. Through a collaboration with Servier, Amgen has rights to commercialize ivabradine in the U.S.

About Amgen's Commitment to Cardiovascular Disease
Amgen is dedicated to addressing important scientific questions in order to advance care and improve the lives of patients with cardiovascular disease. Through its own research and development efforts and innovative partnerships, Amgen has built a robust cardiology pipeline consisting of several investigational molecules in an effort to address a number of today's important unmet patient needs, such as high cholesterol and heart failure.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. 

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

Forward-Looking Statements
This news release contains forward-looking statements that are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties and assumptions that could cause actual results to differ materially from those described. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of Sept. 14, 2014, and expressly disclaims any duty to update information contained in this news release.

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References

Komajda, M, Bohm M, Borer J, et al. Efficacy and Safety of Ivabradine in Patients with Chronic Systolic Heart Failure According to Blood Pressure Level in SHIFT. Euro J Heart Fail. 2014; 16:810-816.

DiFrancesco D and Camm JA. Heart Rate Lowering by Specific and Selective I(f) Current Inhibition With Ivabradine: a New Therapeutic Perspective in Cardiovascular Disease. Drugs. 2004;64(16):1757-1765.

U.S. Food and Drug Administration. Center for Drug Evaluation and Research MAPP 6020.3.http://www.fda.gov/downloads/aboutfda/centersoffices/officeofmedicalproductsandtobacco/cder/manualofpoliciesprocedures/ucm082000.pdf. Accessed August 2014.

Lopez-Sendon, J. The heart failure epidemic. MEDICOGRAPHIA. 2011;33(4):363-369.

Go AS, Mozaffarian D, Roger VL, et al. Heart Disease and Stroke Statistics--2013 Update: a Report From the American Heart Association. Circ. 2013;127:e6-e245.

Jencks, SF, Williams M, Coleman E. Rehospitalizations Among Patients in the Medicare Fee-for-Service Program. NEJM. 2009;360:1418-28.

Swedberg K, Komajda M, Bohm M, et al. Ivabradine and Outcomes in Chronic Heart Failure (SHIFT): a Randomised Placebo Controlled Study. Lancet. 2010; 376:875-85.