Amgen and Cytokinetics Announce Positive Top-Line Results From COSMIC-HF, a Phase 2 Trial of Omecamtiv Mecarbil in Patients With Chronic Heart Failure
THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif.,
The expansion phase of COSMIC-HF was designed to evaluate the pharmacokinetics, pharmacodynamics, safety and tolerability of oral omecamtiv mecarbil in 448 patients with chronic heart failure and left ventricular systolic dysfunction. Data from the expansion phase showed that pharmacokinetic-based dose titration adequately controlled patient exposure to omecamtiv mecarbil and resulted in statistically significant decreases in cardiac dimensions and heart rate in the dose-titration group.
Adverse events, including serious adverse events, in patients on omecamtiv mecarbil appeared comparable to those on placebo. A small increase in troponin was seen among subjects receiving omecamtiv mecarbil. Events of increased troponin were independently adjudicated and none were determined to be myocardial ischemia or infarction. There was no imbalance in deaths, and cardiac adverse events were generally balanced between placebo and active treatment groups.
The full trial results will be submitted to a future medical conference and for publication.
“The positive results from the COSMIC-HF trial of omecamtiv mecarbil are encouraging,” said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. “We are committed to working with Cytokinetics to better understand the data and its potential role in the treatment of heart failure patients.”
“We are pleased that this Phase 2 trial of omecamtiv mecarbil met the objectives related to safety, tolerability, pharmacokinetics and pharmacodynamics in a population of chronic heart failure patients,” said Robert I. Blum, president and CEO at Cytokinetics. “Omecamtiv mecarbil has the potential to offer a new treatment option for patients with heart failure; we look forward to working with Amgen and the medical community to better understand the potential clinical application of this novel drug candidate.”
Heart failure is a common condition that affects more than 23 million people worldwide,3,4 about half of whom have reduced left ventricular function.5 It is the leading cause of hospitalization and readmission in people age 65 and older.6,7 Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.8 An estimated one in five people over the age of 40 are at risk of developing heart failure, and approximately 50 percent of people diagnosed with heart failure will die within five years of initial hospitalization.9,10
COSMIC-HF Trial Design
COSMIC-HF (Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure) is a double-blind, randomized, placebo-controlled, multicenter, Phase 2 trial designed to evaluate an oral formulation of omecamtiv mecarbil in chronic heart failure patients with reduced ejection fraction. The trial consisted of two parts, a dose escalation phase and a larger and longer expansion phase. The dose escalation phase, which completed in 2013, assessed the pharmacokinetics and tolerability of three oral modified-release formulations of omecamtiv mecarbil and was used to select one formulation for further evaluation in the expansion phase. In the dose escalation phase, 96 patients were randomized 1:1:1:1 to placebo or one of three omecamtiv mecarbil oral modified-release formulations in two cohorts (25 mg twice daily or 50 mg twice daily). Each patient cohort was followed for 35 days.
The expansion phase evaluated 448 chronic heart failure patients with reduced ejection fraction who were dosed with the selected oral formulation of omecamtiv mecarbil for 20 weeks and followed for a total of 24 weeks. Patients were randomized 1:1:1 to receive either placebo or treatment with omecamtiv mecarbil 25 mg twice daily or 25 mg with dose escalation to 50 mg twice daily depending on plasma concentrations of omecamtiv mecarbil after two weeks of treatment. The primary endpoints for the expansion phase were to assess the maximum and pre-dose plasma concentration of omecamtiv mecarbil. The secondary endpoints were to assess changes from baseline in systolic ejection time, stroke volume, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, heart rate and N-terminal pro-brain natriuretic peptide (a biomarker associated with the severity of heart failure) at week 20, as well as the safety and tolerability of omecamtiv mecarbil including incidence of adverse events from baseline to week 24.
COSMIC-HF was not designed to assess the impact of omecamtiv mecarbil on cardiovascular outcomes in heart failure patients.
COSMIC-HF was conducted by Amgen in collaboration with Cytokinetics.
About Omecamtiv Mecarbil
Omecamtiv mecarbil is a novel cardiac myosin activator. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting chemical energy into the mechanical force resulting in cardiac contraction. Cardiac myosin activators are thought to accelerate the rate-limiting step of the myosin enzymatic cycle and shift the enzymatic cycle in favor of the force-producing state. Preclinical research has shown that cardiac myosin activators increase contractility in the absence of changes in intracellular calcium in cardiac myocytes.1,2,11
Omecamtiv mecarbil is being developed by Amgen in collaboration with Cytokinetics. Amgen holds an exclusive, worldwide license to omecamtiv mecarbil and related compounds, subject to Cytokinetics’ specified development and commercialization rights. Additionally, Les Laboratoires Servier obtained an exclusive option to commercialize omecamtiv mecarbil in Europe.
About Amgen Cardiovascular
Building on more than three decades of experience in developing biotechnology medicines for patients with serious illnesses, Amgen is dedicated to addressing important scientific questions to advance care and improve the lives of patients with cardiovascular disease, the leading cause of morbidity and mortality worldwide.12 Amgen's research into cardiovascular disease, and potential treatment options, is part of a growing competency at Amgen that utilizes human genetics to identify and validate certain drug targets. Through its own research and development efforts, as well as partnerships, Amgen is building a robust cardiovascular portfolio consisting of several approved and investigational molecules in an effort to address a number of today's important unmet patient needs, such as high cholesterol and heart failure.
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 one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to increase muscle function and contractility. Cytokinetics’ lead drug candidate is tirasemtiv, a fast skeletal muscle activator, for the potential treatment of ALS. Tirasemtiv has been granted orphan drug designation and fast track status by the
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CONTACT: Amgen, Thousand Oaks Kristen Davis, 805-447-3008 (media) Kristen Neese, 805-313-8267 (media) Arvind Sood, 805-447-1060 (investors) CONTACT: Cytokinetics, South San Francisco Diane Weiser, 650-624-3060 (investors and media)