Date: 27-Feb-2020

Amgen, Cytokinetics and Servier announce continuation of GALACTIC-HF following planned interim analysis

Amgen (NASDAQ:AMGN), Cytokinetics, Incorporated (NASDAQ:CYTK) and Servier today announced that the Data Monitoring Committee (DMC) for GALACTIC-HF recently completed the second and final planned interim analysis, which included consideration of pre-specified criteria for futility and superiority. The DMC reviewed data from GALACTIC-HF and recommended that this Phase 3 clinical trial of omecamtiv mecarbil continue without changes to its conduct. The second interim analysis was triggered once a pre-specified number of cardiovascular deaths had occurred in GALACTIC-HF as stipulated by the trial's protocol. A futility analysis allowed the potential for stopping GALACTIC-HF early had the interim analysis shown a low likelihood of the trial demonstrating a clinically meaningful and statistically significant benefit on the primary endpoint in patients receiving omecamtiv mecarbil, plus standard of care, compared to patients receiving placebo plus standard of care. A superiority analysis allowed the potential for stopping the trial early if the primary composite endpoint and the secondary endpoint (time to cardiovascular death) reached statistical significance, adjusting the statistical threshold for interim review.(1) The DMC considers all available evidence in its recommendations regarding trial conduct, and the stopping boundaries provide guidance to the DMC but are not binding rules. GALACTIC-HF, one of the largest Phase 3 global cardiovascular outcomes studies in heart failure ever conducted, has now completed enrollment of more than 8,200 patients in 35 countries who were either hospitalized at the time of enrollment for a primary reason of heart failure, or had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. It is designed to evaluate whether treatment with omecamtiv mecarbil, when added to standard of care, reduces the risk of heart failure events (heart failure hospitalization and other urgent treatment for heart failure) and CV death in patients with heart failure with reduced ejection fraction (HFrEF). About Omecamtiv Mecarbil and the Phase 3 Clinical Trials Program Omecamtiv mecarbil is a novel, selective cardiac myosin activator, also known as a cardiac myotrope,(2) that binds to the catalytic domain of myosin. Preclinical research has shown that cardiac myotropes increase cardiac contractility without affecting intracellular myocyte calcium concentrations or myocardial oxygen consumption.(3-5) 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. Omecamtiv mecarbil is being developed for the potential treatment of heart failure with reduced ejection fraction under a collaboration between Amgen and Cytokinetics, with funding and strategic support from Servier. Omecamtiv mecarbil is the subject of a comprehensive Phase 3 clinical trials program composed of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on cardiovascular outcomes and METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity. About Heart Failure Heart failure is a grievous condition that affects more than 64 million people worldwide(6) about half of whom have reduced left ventricular function.(7,8) It is the leading cause of hospitalization and readmission in people age 65 and older.(9,10) Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.(11) 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.(12,13) About Cytokinetics and Amgen Collaboration In 2006, Cytokinetics and Amgen entered into a strategic alliance to discover, develop and commercialize novel small molecule therapeutics designed to activate the cardiac sarcomere for the potential treatment of heart failure. Omecamtiv mecarbil is being developed by Amgen in collaboration with Cytokinetics, with funding and strategic support from Servier. Amgen holds an exclusive, worldwide license to omecamtiv mecarbil and related compounds, subject to Cytokinetics' specified development and commercialization rights. Cytokinetics is eligible for pre-commercialization and commercialization milestone payments and royalties that escalate based on increasing levels of annual net sales of products commercialized under the agreement. Cytokinetics has co-invested with Amgen in the Phase 3 development program of omecamtiv mecarbil in exchange for increased royalties from Amgen on worldwide sales of omecamtiv mecarbil outside Japan and co-promotion rights in institutional care settings in North America. Amgen has also entered an alliance with Servier for exclusive commercialization rights for omecamtiv mecarbil in Europe as well as the Commonwealth of Independent States, including Russia. Servier contributes funding for development and provides strategic support to the program.