omecamtiv mecarbil (AMG 423) / Royalty, Amgen, Servier, Cytokinetics - LARVOL DELTA

Finerenone Demonstrates Greater Reduction In Heart Failure Events Than Vericiguat And Omecamtiv Mecarbil: A Systematic Review [Poster no. 270] (HFSA 2026) - No abstract available

Review • Cardiovascular • Congestive Heart Failure • Heart Failure

The Impact of Compromised Cardiac Mechanosensing on the Acute and Chronic Effects of Omecamtiv Mecarbil Treatment in Murine HFrEF (AHA 2026) - "Abstract is embargoed at this time."

Preclinical • Cardiovascular

Effect of Omecamtiv Mecarbil According to PREDICT-HF Risk Score: Insights From GALACTIC-HF. (PubMed, JACC Heart Fail) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Low-Normal Hemoglobin Concentrations and Clinical Outcomes in Heart Failure. (PubMed, J Am Coll Cardiol) - P3 | "In patients with HF, hemoglobin concentrations associated with the lowest risk of death and HF hospitalization were approximately 14 g/dL in women and 15 g/dL in men. Hemoglobin concentrations above WHO anemia thresholds may still carry prognostic information and, in conjunction with other clinical findings, may prompt consideration of potentially reversible contributors such as iron deficiency. (Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Added], NCT00634309; Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Alternative], NCT00634400; Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity [CHARM-Preserved], NCT00634712; A Comparison Of Outcomes In Patients In New York Heart Association [NYHA] Class II Heart Failure When Treated With Eplerenone Or Placebo In Addition To Standard Heart Failure Medicines [EMPHASIS-HF], NCT00232180; Irbesartan in..."

Clinical data • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Disorders

Motor Occupancy Defines Emergent Mechanical States in Cardiac Myosin Ensembles. (PubMed, bioRxiv) - "We reconstituted cardiac myosin ensembles and systematically perturbed effective motor occupancy using the small-molecule drugs omecamtiv mecarbil (OM), which prolongs actomyosin interactions, and mavacamten (MAVA), which reduces the number of available force-generating myosin heads. These findings support a model in which cardiac myosin ensembles operate along an occupancy-coordination landscape, where maximal force generation is achieved at an intermediate level of effective motor occupancy. Our results illuminate how changes in motor occupancy are translated into coordinated ensemble mechanics and suggest that emergent mechanical feedback through the shared actin filament may enable ensembles to collectively sense and adapt to their mechanical state."

Journal

Learning Fragment-Based Segmentation of Binding Sites from Molecular Dynamics: A Proof of Concept on Cardiac Myosin. (PubMed, J Chem Inf Model) - "Here, we introduce the Fragment-Based protein Ensemble semantic Segmentation Tool for Myosin (FragBEST-Myo), a deep learning method based on a 3D U-Net architecture, trained to partition the omecamtiv mecarbil (OM) binding site of cardiac myosin into fragment-specific regions using only local shape and physicochemical features...Beyond frame selection, fragment maps provide a compact representation to assess docking poses and to guide fragment-based design. Our proof of concept provides a basis for developing future general models applicable to a broader range of proteins and ligands, with the fragment-based formulation offering a natural route to generalization."

Journal

COMET-HF: Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction (clinicaltrials.gov) - P3 | N=1800 | Recruiting | Sponsor: Cytokinetics

New P3 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

COMET-HF: Study With Omecamtiv Mecarbil (CK-1827452) to Treat Chronic Heart Failure With Severely Reduced Ejection Fraction (clinicaltrials.gov) - P3 | N=1800 | Recruiting | Sponsor: Cytokinetics | N=810 ➔ 1800

Enrollment change • Cardiovascular • Congestive Heart Failure • Heart Failure

Targeting cardiac myosin in HFrEF: mechanism, clinical evidence, and the role of omecamtiv mecarbil. (PubMed, J Cardiothorac Surg) - "OM was generally well-tolerated, with a safety profile comparable to placebo, though it possesses a narrow therapeutic window, with higher plasma concentrations associated with an increased risk of ischemic events. In summary, OM represents a novel, mechanistically distinct therapeutic option for symptomatic HFrEF patients, particularly those with severe systolic dysfunction, who remain at high risk despite optimized GDMT."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure

The role of cardiac myosin activators in dilated cardiomyopathy pharmacotherapy. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Stratifying response to omecamtiv mecarbil in HFrEF using multiscale cardiac digital twins (HEART FAILURE 2026) - "Virtual patient simulations reveal that systolic enhancement is most effective in more severe HFrEF at controlled heart rates, whereas reduced diastolic filling limits benefit during tachycardia regardless of disease severity. These findings provide a mechanistic insight into clinical observations for patient stratification and highlight the importance of heart rate optimization when deploying myosin-targeted therapies in HFrEF."

Cardiovascular • Congestive Heart Failure • Heart Failure

The influence of QRS duration and resynchronization status on the efficacy and safety of omecamtiv mecarbil in heart failure with reduced ejection fraction: the GALACTIC-HF trial (HEART FAILURE 2026) - "Among patients without CRT devices, OM appeared to be less effective in patients with wider QRS ≥ 120 ms, (most of whom would have been clinically eligible for CRT), and this attenuation of benefit appeared to be mitigated by the presence of a CRT device. These post-hoc findings highlight the need to account for intrinsic QRS duration and resynchronization status when selecting patients for OM."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Ising models of cooperativity in muscle contraction. (PubMed, Phys Rev E) - "Our theoretical predictions are successfully tested on experimental data, and our tests also include the condition of hindered filament activation by the use of the specific drug omecamtiv mecarbil (OM). According to our model, the effect of OM results in an anticooperativity mechanism accounting for the experimental data."

Journal

Cytokinetics Announces Nine Upcoming Presentations at the European Society of Cardiology Heart Failure 2026 Congress (The Manila Times) - "Eight presentations, including a late-breaking science oral presentation, are related to MYQORZO (aficamten)....In addition to the rapid fire presentations related to MYQORZO (aficamten), one presentation will offer further insights into the treatment effect of omecamtiv mecarbil in heart failure with reduced ejection fraction (HFrEF)."

P2/3 data • P3 data • Heart Failure • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart. (PubMed, Sci Adv) - "Mavacamten and omecamtiv mecarbil are therapeutic, myosin-targeted drugs designed to treat these myopathies, but their mechanism of action has remained unclear. This remodeling elucidates previously unclear allosteric mechanisms through which these drugs either inhibit or enhance myosin activity, countering the deleterious impacts of disease. These findings reveal how drugs modulate myosin structure to control cardiac contractility."

Journal • Cardiomyopathy • Cardiovascular • Myositis

Toward metabolic precision medicine in heart failure: Timing, tissue specificity, and network reconstruction. (PubMed, Life Sci) - "Compounds such as metformin, Omecamtiv Mecarbil (OM), and SGLT2 inhibitors have demonstrated significant clinical benefits by optimizing energy substrate utilization, improving mitochondrial function, and enhancing autophagy. Future research should prioritize optimizing intervention timing, achieving tissue-specific targeting, and integrating systemic metabolic control to advance the evolution of HF management strategies."

Journal • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Metabolic Disorders

Heart Failure in the Era of Precision Medicine: Advances, Challenges, and Future Directions. (PubMed, Curr Cardiol Rev) - "Advances in HF therapeutics and precision medicine are reshaping patient care. Strategic implementation, equitable access, and continued innovation are critical to improving outcomes across diverse HF populations."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • Congestive Heart Failure • Heart Failure

Mitral regurgitation in patients with heart failure and reduced ejection fraction: insights from GALACTIC-HF. (PubMed, Eur J Heart Fail) - "In GALACTIC-HF, almost 15% of patients with heart failure and reduced ejection fraction had moderate MR, which was associated with a higher risk of the primary outcome."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Differential cardiovascular benefits of SGLT2 inhibitors, sacubitril/valsartan, omecamtiv mecarbil, and vericiguat across heart failure phenotypes: a systematic review and meta-analysis. (PubMed, Front Pharmacol) - "Large-scale randomized trials are warranted to validate these findings. CRD42023455966."

Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension

Dipstick proteinuria and outcomes in patients with heart failure and reduced ejection fraction: insights from GALACTIC-HF. (PubMed, Eur J Heart Fail) - P3 | "In GALACTIC-HF, higher DP levels were independently associated with increased risk of adverse clinical outcomes in patients with reduced ejection fraction."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Renal Disease

Effect of the cardiac myosin activator omecamtiv mecarbil on ventricular arrhythmias, cardiac arrest, and sudden death in heart failure with reduced ejection fraction: the GALACTIC-HF trial. (PubMed, Eur J Heart Fail) - "In this post hoc analysis of the GALACTIC-HF trial, we observed a potential reduction in life-threatening arrhythmia, cardiac arrest, and SD with OM treatment, especially in patients with severely reduced LVEF. These findings require prospective validation in the ongoing COMET-HF trial."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Unveiling Heart Failure: Gender-Specific Insights and Innovations in Women's Cardiac Health. (PubMed, Curr Pharm Des) - "Moreover, it highlights advancements in pharmacological treatments, including ARNI, SGLT2 inhibitors, and novel therapeutic agents like vericiguat (for selective patients) and omecamtiv mecarbil (modest benefits), while addressing the potential of lifestyle interventions, such as diet, exercise, in mitigating HF risk. Artificial intelligence emerges as a promising potential for enhancing diagnostic precision, patient management, and outcome prediction, heralding a new era in HF care. By integrating gender-specific research and innovations, this study aims to refine strategies for improving women's cardiac health, ultimately reducing the global burden of HF."

Journal • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Inflammation

Lactate Dehydrogenase and Outcomes in Patients With HF and Reduced Ejection Fraction: Insights From GALACTIC-HF. (PubMed, JACC Heart Fail) - P3 | "In GALACTIC-HF, higher LDH levels were independently associated with a higher risk of clinical outcomes in HFrEF. (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure [GALACTIC-HF]; NCT02929329; EudraCT number: 2016-002299-28)."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

FHOD3 deficiency disrupts sarcomere organization and activates caMKII signaling in human stem cell-derived cardiomyocytes. (PubMed, Stem Cell Res Ther) - "Our study establishes a valuable human-derived model for investigating the molecular mechanisms of FHOD3 deficiency-induced cardiomyopathy. This model allows for extensive investigation into the phenotypes caused by FHOD3 deficiency and identifies CaMKII activation as a crucial factor contributing to the HF phenotype. Additionally, this model serves as an important tool for discovering novel therapeutic agents, and we demonstrate that OM can partially improve myocardial function in FHOD3 KO hESC-CMs."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Hypertrophic Cardiomyopathy • FHOD3

Phenotype specific nuclear lamina remodeling in hiPSC derived cardiomyocytes bearing TNNT2 sarcomeric variants. (PubMed, iScience) - "These changes in stiffness were rescued by treatment with myosin modulators Mavacamten or Omecamtiv Mecarbil. This study shows that nuclear mechanics is influenced by the interaction between the sarcomere and the cytoskeletal network. Exploring the relationship between contractile dysfunction and nuclear lamina remodeling may reveal new therapeutic targets for cardiomyopathies."

Journal • Cardiomyopathy • LMNA