AMGEN, CYTOKINETICS AND SERVIER ANNOUNCE TOPLINE RESULTS FROM GALACTIC-HF, A PHASE 3 TRIAL OF OMECAMTIV MECARBIL IN PATIENTS WITH HEART FAILURE
Trial Met Primary Composite Endpoint of Reduction in Cardiovascular Death or Heart Failure Events
Trial Did Not Meet Secondary Endpoint of Reduction in Cardiovascular Death
Results Will Be Presented in Late Breaking Clinical Trial Session at AHA Scientific Sessions 2020
THOUSAND OAKS, Calif., SOUTH SAN FRANCISCO, Calif., and SURESNES, France., Oct. 08, 2020 – Amgen (NASDAQ:AMGN), Cytokinetics, Incorporated (NASDAQ:CYTK) and Servier today announced topline results from GALACTIC-HF, a Phase 3 pivotal clinical trial of omecamtiv mecarbil in patients with heart failure with reduced ejection fraction (HFrEF).
The results of GALACTIC-HF show that treatment with omecamtiv mecarbil achieved the primary composite efficacy endpoint and demonstrated a statistically significant effect to reduce cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care (HR: 0.92; 95% CI: 0.86, 0.99, p=0.0252).
No reduction in the secondary endpoint of CV death was observed. Adverse events, including major ischemic cardiac events, were balanced between treatment arms. Additional analyses of data are underway and results from GALACTIC-HF will be presented at the American Heart Association (AHA) Scientific Sessions 2020, in a virtual Late Breaking Clinical Trial session on Friday, November 13, 2020 from 10:35-10.45 a.m. CDT.
Omecamtiv mecarbil is an investigational cardiac myosin activator, the first of a novel class of myotropes1 designed to directly target the contractile mechanisms of the heart.
“The outcomes observed in GALACTIC-HF further the understanding of treating heart failure, a devastating disease in which half of heart failure patients will die within five years of initial hospitalization,” said David M. Reese, M.D. executive vice president of Research and Development at Amgen. “At Amgen, we remain committed to developing and delivering transformative medicines that improve the lives of patients with cardiovascular disease.”
“GALACTIC-HF provides insights into effects associated with targeting cardiac muscle contractility with omecamtiv mecarbil to treat heart failure patients with reduced ejection fraction,” said Fady I. Malik, M.D., Ph.D., Cytokinetics’ executive vice president of Research & Development. “We are grateful to the trial investigators, site personnel, patients and caregivers who participated in the trial, and we look forward to further data analyses and the presentation of the results of this Phase 3 trial at the American Heart Association Scientific Sessions.”
“Heart failure is a devastating condition jeopardizing patients’ lives every day. We are pleased to have collaborated with Amgen and Cytokinetics on one of the largest heart failure trials ever conducted to investigate this novel therapy in patients with heart failure. It is important to now turn our attention to fully analyzing the data from this important study in this clinical setting,” said Claude Bertrand, PharmD, PhD, Executive Vice President R&D at Servier.
GALACTIC-HF: Trial Design
GALACTIC-HF,2 (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), one of the largest Phase 3 global cardiovascular outcomes studies in heart failure ever conducted, enrolled 8,256 patients in 35 countries with HFrEF, New York Heart Association (NYHA) class II-IV, left ventricular ejection fraction (LVEF) ≤35%, elevated natriuretic peptides and either current hospitalization for heart failure or history of hospitalization or emergency department visit for heart failure within a year. Patients were randomized to either oral placebo or a starting dose of 25 mg omecamtiv mecarbil twice daily (maintenance dose of 50 mg, 37.5 mg, or 25 mg twice daily) guided by pharmacokinetic-guided dose selection. A blood test, the QMS Omecamtiv Mecarbil Immunoassay (the OM Test) was used to measure plasma levels of omecamtiv mecarbil in each patient in order to guide selection of the appropriate maintenance dose.
The primary composite endpoint of this double-blind, placebo-controlled, event-driven trial was time to CV death or first heart failure event (heart failure hospitalization and other urgent treatment for heart failure). Secondary endpoints were: time to CV death, patient reported outcomes (measured by Kansas City Cardiomyopathy Questionnaire [KCCQ] Total Symptom Score [TSS]), time to first heart failure hospitalization and time to all-cause death.
About Omecamtiv Mecarbil and the Phase 3 Clinical Trials Program
Omecamtiv mecarbil is an investigational selective cardiac myosin activator, the first of a novel class of myotropes1 designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing 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 (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 composed of GALACTIC-HF 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 worldwide6 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.
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.
Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors 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 impact muscle function and contractility. Cytokinetics is collaborating with Amgen Inc. (Amgen) to develop omecamtiv mecarbil, a novel cardiac muscle activator. Omecamtiv mecarbil is the subject of an international clinical trials program in patients with heart failure including GALACTIC-HF and METEORIC-HF. Amgen holds an exclusive worldwide license to develop and commercialize omecamtiv mecarbil with a sublicense held by Servier for commercialization in Europe and certain other countries. Cytokinetics is developing reldesemtiv, a fast skeletal muscle troponin activator (FSTA) for the potential treatment of ALS and other neuromuscular indications following conduct of FORTITUDE-ALS and other Phase 2 clinical trials. The company is considering potential advancement of reldesemtiv to Phase 3 pending ongoing regulatory interactions. Cytokinetics is collaborating with Astellas Pharma Inc. (Astellas) to research, develop and commercialize other novel mechanism skeletal sarcomere activators (not including FSTAs). Licenses held by Amgen and Astellas are subject to specified co-development and co-commercialization rights of Cytokinetics. Cytokinetics is also developing CK-274, a novel cardiac myosin inhibitor that company scientists discovered independent of its collaborations, for the potential treatment of hypertrophic cardiomyopathies. Cytokinetics has granted Ji Xing Pharmaceuticals Limited an exclusive license to develop and commercialize CK-274 in China and Taiwan, in accordance with Cytokinetics’ planned global registration programs. Cytokinetics is conducting REDWOOD-HCM, a Phase 2 clinical trial of CK-274 in patients with obstructive HCM. Cytokinetics continues its over 20-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness.
For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on Twitter, LinkedIn, Facebook and YouTube.
Amgen Forward-Looking Statements
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Cytokinetics Forward-Looking Statements
This press release contains forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995 (the “Act”). Cytokinetics disclaims any intent or obligation to update these forward-looking statements, and claims the protection of the Act’s Safe Harbor for forward-looking statements. Examples of such statements include, but are not limited to, statements relating to GALACTIC-HF; the potential benefits of omecamtiv mecarbil, including its ability to represent a novel therapeutic strategy to increase cardiac muscle function and restore cardiac performance; the approval of omecamtiv mecarbil by the FDA or any other regulatory agency; the successful marketing and commercialization of omecamtiv mecarbil; Cytokinetics’ and its partners’ research and development activities; the design, timing, results, significance and utility of preclinical and clinical results; and the properties and potential benefits of Cytokinetics’ drug candidates. Such statements are based on management’s current expectations and beliefs, but actual results may differ materially due to various risks and uncertainties, including, but not limited to, potential difficulties or delays in the development, testing, regulatory approvals for trial commencement, progression or product sale or manufacturing, or production of Cytokinetics’ drug candidates that could slow or prevent clinical development or product approval; the impact of the COVID-19 pandemic on our research and development activities and business operations, Cytokinetics’ drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics’ or its partners’ ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; Amgen’s decisions with respect to the design, initiation, conduct, timing and continuation of development activities for omecamtiv mecarbil; standards of care may change, rendering Cytokinetics’ drug candidates obsolete; competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics’ drug candidates and potential drug candidates may target; and risks and uncertainties relating to the timing and receipt of payments from its partners, including milestones and royalties on future potential product sales under Cytokinetics’ collaboration agreements with such partners. For further information regarding these and other risks related to Cytokinetics’ business, investors should consult Cytokinetics’ filings with the Securities and Exchange Commission.
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1. Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.
2. Teerlink JR., Diaz R., Felker GM., et al. Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction: Rationale and Design of GALACTIC-HF. JACC Heart Fail. 2020 Apr; 8(4):329-340.
doi: 10.1016/j.jchf.2019.12.001.Epub 2020 Feb 6.
3. Planelles-Herrero VJ, Hartman JJ, Robert-Paganin J. et al. Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. 2017;8:190.
4. Shen YT, Malik FI, Zhao X, et al. Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure.Circ Heart Fail. 2010; 3: 522-27.
5. Malik FI, Hartman JJ, Elias KA, Morgan BP, Rodriguez H, Brejc K, Anderson RL, Sueoka SH, Lee KH, Finer JT, Sakowicz R. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure.Science. 2011 Mar 18;331(6023):1439-43.
6. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858.
7. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327.
8. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–2200.
9. Roger VL. Epidemiology of Heart Failure.Circulation Research. 2013;113:646-659, originally published August 29, 2013. Doi: 10.1161/CIRCRESAHA.113.300268.
10. Kilgore M, Patel HK, Kielhorn A et al. Economic burden of hospitalizations ofMedicare beneficiaries with heart failure. Risk Manag Healthc Policy. 2017; 10: 63-70.
11. Jhund PS, MacIntyre K, Simpson CR, et al. Long-Term Trends in First Hospitalization for Heart Failure and Subsequent Survival Between 1986 and 2003. Circulation. 2009;119:515-523.
12.Benjamin EJ, Virani SS, Callaway CW et al. Heart Disease and Stroke Statistics—2018 Update: A Report From the American Heart Association. Circulation. 2018;137:e67-e492.
13. Roger VL, Weston SA, Redfield MM, et al. Trends in Heart Failure Incidence and Survival in a Community-Based Population. JAMA. 2004;292:344-350.