Metoprolol Tartrate

Two New Analyses from SEQUOIA-HCM Demonstrate Treatment with Aficamten Improves Post-Exercise Oxygen Uptake Recovery and Quality of Life New Data from FOREST-HCM Demonstrate Aficamten Durably Reduces the Proportion of Patients Guideline Eligible for Septal Reduction Therapy Analyses of Real-World Data Reveal Cost of Care Differences in HCM Across Gender, Age and Race/Ethnicity SOUTH SAN FRANCISCO, Calif., Nov. 16, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced new data relating to aficamten and hypertrophic cardiomyopathy (HCM), were presented at the American Heart Association Scientific Sessions 2024 in Chicago, IL. “These analyses add to the growing body of evidence supporting the safety and efficacy profile of aficamten and build upon primary findings related to peak VO2 and improvement in health-related quality of life, while demonstrating a significant and durable reduction in the need for septal reduction therapy,” said Stephen Heitner, M.D., Vice President, Head of Clinical Research. “In addition, analyses presented of real-world data shed light on the disparities that exist in the cost of care for HCM, underscoring the need for improved equity in healthcare across gender and race.” Treatment with Aficamten Improves VO2 Recovery Data from a pre-specified exploratory analysis from SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM) presented today showed that treatment with aficamten from baseline to Week 24 resulted in significantly shortened post-exercise oxygen-uptake (VO2) recovery (VO2Rec). Prolonged VO2Rec has previously been linked to adverse outcomes in patients with other forms of heart failure. The analysis demonstrated that treatment with aficamten significantly shortened times for VO2Rec to decline by 12.5% (VO2Rec T12.5%), 25% (VO2Rec T25%) and 50% (VO2Rec T50%) of peak VO2, corresponding to absolute reductions relative to placebo of 8 seconds (p<0.001), 7 seconds (p<0.001) and 8 seconds (p=0.01), respectively (Table 1). Additionally, a decrease in VO2Rec T12.5% corresponded to a decrease in NT-proBNP levels (p<0.001), high-sensitivity cardiac troponin I levels (hs-cTnI) (p<0.001), resting left ventricular outflow tract gradient (LVOT-G) (p=0.003) and Valsalva LVOT-G (p=0.003). Table 1. Effect of Aficamten on Post-Exercise Oxygen Uptake Recovery in Patients with Obstructive HCM AFICAMTENPLACEBO VariablenBaselineWeek 24Absolute difference (SD)nBaselineWeek 24Absolute difference (SD)Treatment Effect (95% CI)p-valuePeakVO2 (mL/kg/min)13318.4 ± 4.520.2 ± 5.21.8 ± 3.113018.6 ± 4.618.6 ± 4.70.0 ± 2.71.7 (1.0, 2.4)p<0.001VO2Rec Delay 0% (s)13419 ± 2015 ± 18-4 ± 1912917 ± 1918 ± 191 ± 19-4 (-8, -0)p=0.047VO2recovery 12.5% (s)12645 ± 2038 ± 18-7 ± 1912745 ± 2246 ± 231 ± 16-8 (-12, -5)p<0.001VO2recovery 25% (s)12366 ± 2160 ± 19-6 ± 1812670 ± 2770 ± 28-0 ± 17-7 (-11, -3)p<0.001VO2recovery 50% (s)117115 ± 32107 ± 32-8 ± 27116116 ± 38116 ± 360 ± 26-8 (-15, -2)p=0.01 Treatment with Aficamten Results in Sustained and Significant Improvements in Health-Related Quality of Life Data were also presented from an additional pre-specified exploratory analysis of SEQUOIA-HCM that evaluated the effect of aficamten on patient-reported health status using two quality of life (QoL) measurements, EuroQol 5-Dimension 5-Level (EQ-5D-5L) and EuroQol Visual Analogue Scale (EQ-VAS). EQ-5D-5L (range from 0 to 1) and EQ-VAS (range from 0 to 100) were measured at baseline through Week 24, with higher scores indicating better QoL. At baseline, there were no differences between patients receiving aficamten and placebo in any of the five domains of the EQ-5D-5L index. Treatment with aficamten improved the EQ-5D-5L index score by 0.04 (p=0.008) and the EQ-VAS score by 4.5 points (p=0.002) compared to placebo, with significant differences observed as early as eight weeks after treatment initiation (p=0.005). Following withdrawal of treatment at the end of the clinical trial, QoL benefits in patients who were receiving aficamten subsequently decreased. These data demonstrate that treatment with aficamten yielded early, sustained and significant improvement in overall health-related QoL among patients with obstructive HCM as measured by EQ-5D-5L, reinforcing previously reported data showing that aficamten improves QoL as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ). Treatment with Aficamten Durably Reduces SRT-Eligibility After 12 Weeks in Open-Label Extension Findings from an analysis from FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM), the open-label extension clinical study of aficamten in patients with HCM, related to the efficacy and safety of aficamten in patients who at baseline were guideline-eligible for septal reduction therapy (SRT) were also presented. Of the 280 patients with obstructive HCM enrolled in FOREST-HCM with ≥12 weeks of follow-up at the time of this analysis, 97 (35%) met guideline eligibility criteria for SRT at baseline; after 12 weeks of treatment with aficamten, only 3 (3%) remained SRT guideline-eligible. When comparing those patients who were SRT guideline-eligible versus those who were not at baseline, there were similar, robust improvements in KCCQ, New York Heart Association (NYHA) Functional Class, NT-proBNP and resting and Valsalva left ventricular outflow tract (LVOT) gradient. Changes in left ventricular ejection fraction (LVEF) were modest and similar between SRT-eligible and SRT-ineligible patients. Instances of LVEF <50% and atrial fibrillation or flutter were rare, and similar between groups. These results demonstrate that treatment with aficamten may provide a safe, durable and effective alternative to SRT in many patients with obstructive HCM. Analyses of Real-World Data Reveals Differences in Costs Across Gender, Age and Race/Ethnicity in Patients with Obstructive HCM A new health economics and outcomes research (HEOR) study presented today evaluated the impact of sociodemographic characteristics on cost of care in patients with obstructive HCM. These retrospective analyses included adults diagnosed with obstructive HCM from January 2013 to December 2021 using real-world data from Optum Market Clarity database. Among 5,129 patients identified with obstructive HCM, 52% were female, the mean age was 63.9 years, 77.6% were white and 40% were Medicare recipients. Compared to females, male patients had higher costs including overall total ($71,581 vs $63,710; p=0.014), medical ($70,395 vs $62,455; p=0.013), ambulatory ($16,024 vs $10,776; p<0.001), office visits ($1,906 vs $1,573; p<0.001) and outpatient visits ($14,118 vs $9,202; p<0.001). Compared to white patients, Black patients had significantly higher inpatient admissions costs ($54,572 vs $42,686; p=0.015), Hispanic patients had greater emergency room costs ($1,724 vs $791; p<0.001) and Asian patients had greater office costs ($2,094 vs $1,800; p<0.001). Patients aged 18-39 years had higher costs across all categories (p<0.001) compared to patients 40 or older, except inpatient admissions and prescriptions. Overall, these real-world analyses showed that, for patients with obstructive HCM, being a younger male was associated with increased healthcare costs, with additional differences in cost across race/ethnicity. About Aficamten Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten was evaluated in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a positive pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China. Cytokinetics submitted a New Drug Application (NDA) to the FDA in Q3 2024 and expects to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in Q4 2024. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, and CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. About Hypertrophic Cardiomyopathy Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed, however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed in the U.S.1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.4 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.5 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation. About Cytokinetics Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial evaluating aficamten, a next-in-class cardiac myosin inhibitor, in obstructive hypertrophic cardiomyopathy (HCM), Cytokinetics submitted an NDA for aficamten to the U.S. Food & Drug Administration and is progressing regulatory submissions for aficamten for the treatment of obstructive HCM in Europe. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of heart failure with preserved ejection fraction (HFpEF), and CK-089, a fast skeletal muscle troponin activator (FSTA) for the potential treatment of a specific type of muscular dystrophy. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. 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 express or implied relating to the properties or potential benefits of aficamten or any of our other drug candidates, our ability to obtain regulatory approval for aficamten for the treatment of obstructive hypertrophic cardiomyopathy or any other indication from FDA or any other regulatory body in the United States or abroad, and the labeling or post-marketing conditions that FDA or another regulatory body may require in connection with the approval of aficamten. Such statements are based on management’s current expectations, but actual results may differ materially due to various risks and uncertainties, including, but not limited to the risks related to Cytokinetics’ business outlines in Cytokinetics’ filings with the Securities and Exchange Commission. Forward-looking statements are not guarantees of future performance, and Cytokinetics’ actual results of operations, financial condition and liquidity, and the development of the industry in which it operates, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that Cytokinetics makes in this press release speak only as of the date of this press release. Cytokinetics assumes no obligation to update its forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release. CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:Cytokinetics Diane WeiserSenior Vice President, Corporate Affairs(415) 290-7757 References: CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575Symphony Health 2016-2021 Patient Claims Data DoF;Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21

SOUTH SAN FRANCISCO, Calif., Nov. 16, 2024 (GLOBE NEWSWIRE) -- Cytokinetics, Incorporated (Nasdaq: CYTK) today announced new data from post-hoc analyses of GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil were presented at the American Heart Association Scientific Sessions 2024 in Chicago, IL. “These analyses reinforce the potential treatment benefit of omecamtiv mecarbil in patients from GALACTIC-HF who are at higher risk, such as older patients or those with a recent ventricular arrhythmia,” said Stuart Kupfer, M.D., Senior Vice President, Chief Medical Officer. “As we prepare for the start of COMET-HF, the confirmatory Phase 3 clinical trial of omecamtiv mecarbil, we look forward to evaluating its potential to reduce the risk of adverse heart failure outcomes across the spectrum of these very high-risk patients failing guideline-directed medical therapy.” Treatment with Omecamtiv Mecarbil Reduced Risk of the Primary Composite Endpoint in Patients with Severe Heart Failure Independent of Age A post-hoc analysis from GALACTIC-HF supports the potential efficacy of omecamtiv mecarbil irrespective of age, including in patients with severe heart failure. Of the 8,232 patients included in the analysis, patients were on average 64.5 years old, with 54.5% aged ≥65 years. At baseline, patients aged ≥65 years were more likely to be women, have atrial fibrillation or flutter, have worse New York Heart Association (NYHA) Functional Class and have higher NT-proBNP as compared to patients aged <65 years. Over a median follow-up period of 21.8 months, the primary composite endpoint of cardiovascular death or heart failure events occurred at a rate of 21.4 per 100 patient years among patients <65 years, and 28.8 per 100 patient years in patients ≥65 years. In the overall study population, the treatment effect of omecamtiv mecarbil was similar across age groups (interaction p=0.73). In patients with severe heart failure, omecamtiv mecarbil reduced the risk for the primary outcome independent of age group (HR 0.77; 95% CI, 0.64-0.92 and HR 0.83; 95% CI, 0.71-0.97 for patients <65 years and ≥65 years respectively; interaction p=0.72). These relative risk reductions were associated with large absolute risk reductions (8.6 and 7.9, respectively). Additionally, adverse events of special interest, such as ventricular arrhythmias (VA) and myocardial ischemic events were similar between omecamtiv mecarbil and placebo in both age groups. Ventricular Arrythmias Associated with Adverse Clinical Outcomes in Patients with Heart Failure and Reduced Ejection Fraction; Treatment with Omecamtiv Mecarbil Reduces Risk of Ventricular Arrythmias in Patients with Severely Reduced LVEF A second post-hoc analysis from GALACTIC-HF investigated clinical consequences of ventricular arrhythmias (VA) in the patients studied in GALACTIC-HF. Of the 8,232 patients enrolled in GALACTIC-HF, following an occurrence of VA, there was a significantly higher risk of the primary endpoint of cardiovascular death or heart failure events (HR 1.67; 95% CI 1.42-1.97; p<0.001) and all-cause mortality (HR 2.07; 95% CI 1.77-2.42; p<0.001). Treatment with omecamtiv mecarbil was not associated with an increase in the occurrence of VA and the occurrence of VA in participants treated with omecamtiv mecarbil did not impart worse prognosis than those with VA compared to placebo. Of note, participants with lower LVEF had an increased risk of VA, and in those participants, treatment with omecamtiv mecarbil appeared to reduce the risk for the composite outcome of VA, cardiac arrest and sudden death (LVEF ≤28%, HR 0.77, 95% CI 0.63-0.94; p=0.009, Figure 1). Overall, these findings support the safety of omecamtiv mecarbil with regards to VA as well as a potential benefit in patients with severely reduced LVEF and are consistent with the findings of increased treatment effect of omecamtiv mecarbil in patients with severely reduced LVEF. About Omecamtiv Mecarbil Omecamtiv mecarbil is an investigational, selective, small molecule 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. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.2-4 The development program for omecamtiv mecarbil assessed its potential for the treatment of HFrEF. Positive results from GALACTIC-HF, the first Phase 3 clinical trial of omecamtiv mecarbil demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of 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. No reduction in the secondary endpoint of time to CV death was observed. In general, the overall rates of myocardial ischemia, ventricular arrhythmias and death were similar between treatment and placebo groups. Adverse events and treatment discontinuation of study drug were balanced between treatment arms. The magnitude of the treatment effect in a pre-specified subgroup of more than 4,000 patients with heart failure with severely reduced ejection fraction (<30%) was observed to be greater than in the overall drug treated population of GALACTIC-HF. Omecamtiv mecarbil will be the subject of COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a confirmatory Phase 3 clinical trial in patients with symptomatic heart failure with severely reduced ejection fraction, expected to start in Q4 2024. About Heart Failure with Severely Reduced Ejection Fraction Heart failure is a grievous condition that affects more than 64 million people worldwide5 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 By 2029 is it estimated that 2.8 million people in the U.S. will have heart failure with severely reduced ejection fraction10, characterized as heart failure with reduced ejection fraction (HFrEF) <30%, and 840,000 people will have severely reduced ejection fraction with other features indicative of high risk heart failure.11 Patients with high risk heart failure with severely reduced ejection fraction account for approximately 60% of all HFrEF hospitalizations, with 35% of patients re-hospitalized within a year. 12,13 About Cytokinetics Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact myocardial muscle function and contractility. Following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial evaluating aficamten, a next-in-class cardiac myosin inhibitor, in obstructive hypertrophic cardiomyopathy (HCM), Cytokinetics submitted an NDA for aficamten to the U.S. Food & Drug Administration and is progressing regulatory submissions for aficamten for the treatment of obstructive HCM in Europe. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM. Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure with severely reduced ejection fraction (HFrEF), CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of heart failure with preserved ejection fraction (HFpEF), and CK-089, a fast skeletal muscle troponin activator (FSTA) for the potential treatment of a specific type of muscular dystrophy. For additional information about Cytokinetics, visit www.cytokinetics.com and follow us on X, LinkedIn, Facebook and YouTube. 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, express or implied, relating to the Company’s development plans for omecamtiv mecarbil in the United States. Such statements are based on management's current expectations, 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; Cytokinetics' drug candidates may have adverse side effects or inadequate therapeutic efficacy; the FDA or foreign regulatory agencies may delay or limit Cytokinetics' ability to conduct clinical trials; Cytokinetics may be unable to obtain or maintain patent or trade secret protection for its intellectual property; standards of care may change, rendering Cytokinetics' drug candidates obsolete; and competitive products or alternative therapies may be developed by others for the treatment of indications Cytokinetics' drug candidates and potential drug candidates may target. For further information regarding these and other risks related to Cytokinetics' business, investors should consult Cytokinetics' filings with the Securities and Exchange Commission. CYTOKINETICS® and the C-shaped logo are registered trademarks of Cytokinetics in the U.S. and certain other countries. Contact:Cytokinetics Diane WeiserSenior Vice President, Corporate Affairs(415) 290-7757 References: Psotka MA, Gottlieb SS, Francis GS et al. Cardiac Calcitropes, Myotropes, and Mitotropes. JACC. 2019; 73:2345-53.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.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.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.James et al. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018; 392: 1789–858.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. 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.Roger VL. Epidemiology of Heart Failure. Circulation Research. 2013;113:646-659, originally published August 29, 2013. doi: 10.1161/CIRCRESAHA.113.300268.Kilgore M, Patel HK, Kielhorn A, et al. Economic burden of hospitalizations of Medicare beneficiaries with heart failure. Risk Manag Healthc Policy. 2017; 10: 63-70. Taylor C J, Ordóñez-Mena J M, Roalfe A K, et al. Trends in survival after a diagnosis of heart failure in the United Kingdom 2000-2017: population based cohort study. BMJ 2019; 364:l223 doi:10.1136/bmj.l223Greene SJ, Bauersachs J, Brugts JJ, et al. Worsening Heart Failure: Nomenclature, Epidemiology, and Future Directions: JACC Review Topic of the Week. JACC. 2023 Jan 31;81(4):413-424. doi:10.1016/j.jacc.2022.11.023. PMID: 36697141.Extrapolated from Desai NR, Butler J, Binder G, et al. Prevalence and Excess Risk of Hospitalization in Heart Failure with Reduced Ejection Fraction. Poster presented at: Heart Failure Society of America (HFSA) Annual Scientific Meeting; 2022 Sep 30-Oct 3; Washington, DC.Carnicelli AP, Clare RM, Hofmann P, et al. Clinical trajectory of patients with a worsening heart failure event and reduced ventricular ejection fraction. Am Heart J. 2022 Mar; 245:110-116. doi: 10.1016/j.ahj.2021.12.003. Epub 2021 Dec 18. PMID: 34932997. A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/ee1006b4-fa47-4800-8929-5cdb837d546e