Amgen, Cytokinetics and Servier announce start of METEORIC-HF, the second Phase 3 clinical trial of omecamtiv mecarbil in patients with heart failure

Amgen (NASDAQ: AMGN), Cytokinetics, Incorporated (NASDAQ: CYTK) and Servier today announced that METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), the second Phase 3 clinical trial of omecamtiv mecarbil, a novel cardiac myosin activator, is open to enrollment. Omecamtiv mecarbil is being developed for the potential treatment of heart failure with reduced ejection fraction (HFrEF).

METEORIC-HF is designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) in patients with HFrEF. Cytokinetics is conducting METEORIC-HF in collaboration with Amgen, with funding and strategic support from Servier.

"The start of this second Phase 3 clinical trial marks an important milestone in the expansion of our clinical trials program for omecamtiv mecarbil, testing the hypothesis that improving cardiac function with a drug candidate that directly increases myocardial contractility may improve exercise capacity," said Fady I. Malik, M.D., Ph.D., executive vice president of Research & Development at Cytokinetics. "Exercise intolerance, typically manifested by shortness of breath and fatigue on exertion, is a predominant symptom of chronic heart failure and often the first symptom that prompts patients to seek medical care. If positive, this clinical trial may provide key clinically relevant evidence."

METEORIC-HF Clinical Trial Design

METEORIC-HF is a Phase 3, randomized, placebo-controlled, double-blind, parallel group, multicenter clinical trial designed to evaluate the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET) following 20 weeks of treatment. The trial is designed to enroll approximately 270 patients with HFrEF at sites throughout the U.S., Canada and Europe. In order to be eligible to participate in METEORIC-HF, patients must have a left ventricular ejection fraction (LVEF) =35 percent, be New York Heart Association (NYHA) heart failure class II or III and have reduced exercise capacity compared to age matched controls. Patients will be randomized in a 2:1 fashion to omecamtiv mecarbil, which will be started at 25 mg twice daily and titrated to 25, 37.5 or 50 mg twice daily based on the same PK-guided dosing regimen as is used in GALACTIC-HF, the ongoing Phase 3 cardiovascular outcomes trial of omecamtiv mecarbil, or to placebo. The primary endpoint is the change in peak oxygen uptake (pVO2) on CPET from baseline to Week 20. Secondary endpoints include the change in total workload during CPET from baseline to Week 20 and the change in the average daily activity units measured over a 2-week period from baseline (Week -2 to Day 1) to Week 18-20 as determined using accelerometry.

About Omecamtiv Mecarbil and the Phase 3 Clinical Trials Program

Omecamtiv mecarbil is a novel, selective cardiac myosin activator that binds to the catalytic domain of myosin. Preclinical research has shown that cardiac myosin activators increase cardiac contractility without affecting intracellular myocyte calcium concentrations or myocardial oxygen consumption.(1,2,3) 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 (HFrEF) 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 comprised of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), a large, Phase 3 global cardiovascular outcomes study, and METEORIC-HF. Amgen is conducting GALACTIC-HF in collaboration with Cytokinetics and Servier.

GALACTIC-HF is designed to enroll approximately 8,000 patients at over 900 sites in 35 countries who are either currently hospitalized for a primary reason of heart failure or have had a hospitalization or admission to an emergency room for heart failure within one year prior to screening. The trial 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 cardiovascular (CV) death in patients with chronic heart failure with reduced ejection fraction.

Enrollment in GALACTIC-HF is nearing 90 percent completion, with over 7,000 patients randomized to date from across the spectrum of the NYHA classification (class II to IV). Completion of patient enrollment in GALACTIC-HF is expected to occur during the first half of 2019.

About Heart Failure

Heart failure is a grievous condition that affects more than 26 million people worldwide,(4,5) about half of whom have reduced left ventricular function.(6,7) It is the leading cause of hospitalization and readmission in people age 65 and older.(8,9) Despite broad use of standard treatments and advances in care, the prognosis for patients with heart failure is poor.(10) 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.(11,12)

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 in Europe as well as the Commonwealth of Independent States, including Russia. Servier contributes funding for development and provides strategic support to the program.

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