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

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

Stratifying response to omecamtiv mecarbil in HFrEF using multiscale cardiac digital twins (HEART FAILURE 2026) - No abstract available

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) - No abstract available

Clinical • 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

Multiple-Dose Up-Titration Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Omecamtiv Mecarbil in Healthy Chinese Subjects. (PubMed, Drugs R D) - "Omecamtiv mecarbil was well tolerated at the dose levels of 25-50 mg in healthy Chinese participants according to a pharmacokinetic-based titration scheme. Exposure of omecamtiv mecarbil was dose proportional, and no dose-related trends were observed in treatment-emergent adverse events."

Journal • PK/PD data • Cardiovascular

Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart. (PubMed, bioRxiv) - "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

Lactate dehydrogenase and clinical outcomes in patients with heart failure and reduced ejection fraction: Insights from the GALACTIC-HF trial (AHA 2025) - "However, whether LDH levels are also prognostically important in heart failure (HF) is unknown.Hypothesis:LDH concentration is associated with fatal and non-fatal outcomes in patients with HF and reduced ejection fraction (HFrEF).GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) was a randomized, double-blind, multicenter, event-driven trial that evaluated the efficacy and safety of the cardiac myosin activator, omecamtiv mecarbil (OM) versus placebo in 8,232 patients with HFrEF...In GALACTIC-HF, higher LDH levels were independently associated with increased risk of fatal and non-fatal outcomes in patients with HFrEF."

Clinical • Clinical data • Cardiovascular • Congestive Heart Failure • Heart Failure

A dual in silico framework for cardiac drug evaluation to assess electrophysiological and mechanical responses. (PubMed, J Physiol) - No abstract available

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Continued conduct of COMET-HF (Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure), a confirmatory Phase 3 clinical trial of omecamtiv mecarbil in patients with symptomatic heart failure with severely reduced ejection fraction. (The Manila Times) - "We expect to continue patient enrollment through 2026."

Enrollment status • Heart Failure

Semiquantitative urine dipstick protein assessments predict clinical outcomes in patients with heart failure and reduced ejection fraction: Insights from the GALACTIC-HF trial (AHA 2025) - "Given the renewed emphasis on CV-metabolic-kidney overlap in medicine, we have examined the prognostic value of semiquantitative urine dipstick protein (DP) assessments in patients with heart failure and reduced ejection fraction (HFrEF).Hypothesis:DP predicts clinical outcomes and enables risk stratification in HFrEF.GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) was a randomized, double-blind, multicenter, event-driven trial that evaluated the efficacy and safety of the cardiac myosin activator omecamtiv mecarbil (OM) versus placebo in 8,232 patients with HFrEF...DP is a simple inexpensive test with prognostic value in HFrEF."

Clinical • Clinical data • Cardiovascular • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Heart Failure • Metabolic Disorders • Nephrology • Renal Disease

Efficacy of cardiac myosin activators compared to placebo in patients with heart failure and reduced ejection fraction: A systematic review and meta-analysis of randomized controlled trials. (PubMed, Heart Lung) - "CMAs, particularly omecamtiv mecarbil, did not significantly impact all-cause mortality, cardiovascular death, or HF recurrence in patients with HFrEF. However, modest reductions were observed in composite outcomes and stroke. These findings should be interpreted cautiously, and further trials are needed to validate their clinical role."

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

Efficacy and Safety of Omecamtiv Mecarbil in Heart Failure With Reduced Ejection Fraction According to Age: The GALACTIC-HF Trial. (PubMed, JACC Heart Fail) - P3 | "In GALACTIC-HF, older individuals were well-represented and faced higher risks of CV events. Treatment with omecamtiv mecarbil was safe irrespective of age and reduced the risk of CV death or first HF event across the age spectrum, especially in those with severe HF. (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure [GALACTIC-HF]; NCT02929329.)."

Journal • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure

Confirmation of Omecamtiv Mecarbil Efficacy Trial in Heart Failure (COMET-HF): A Phase 3, Randomized, Placebo-Controlled Clinical Trial (HFSA 2025) - "In this multicenter, randomized, placebo-controlled clinical trial, patients will be randomized 1:1 between omecamtiv mecarbil and placebo. The primary composite endpoint is time to a first heart failure event, cardiovascular death, left ventricular assist device implantation, heart transplantation, or stroke."

Clinical • P3 data • Cardiovascular • Congestive Heart Failure • Heart Failure

Breaking new ground in heart failure management: novel therapies and future frontiers. (PubMed, Front Cardiovasc Med) - "Emerging pharmacological therapies in heart failure management include SGLT-2 inhibitors, ARNI, Vericiguat, and Omecamtiv. Other novel therapies that are changing the scope of HF management include IV Iron therapy and new antifibrotic agents, such as pirfenidone and pamrevlumab...Additionally, the limitations and challenges associated with the emerging therapies will be discussed. Overall, this literature review aims to provide a comprehensive understanding of how these therapies are transforming the management of HF and related cardiomyopathies."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Gene Therapies • Heart Failure

Serum magnesium and outcomes in patients with heart failure and reduced ejection fraction: insights from the GALACTIC-HF trial (ESC-WCC 2025) - " GALACTIC-HF was a randomised, double-blind, multicentre, event-driven trial that investigated the efficacy and safety of the cardiac myosin activator omecamtiv mecarbil (OM) compared to placebo in patients with HF and a left ventricular ejection fraction (LVEF) ≤35%... In GALACTIC-HF, 10.7% of patients with HFrEF had hypermagnesemia, which was associated with a higher risk of the primary outcome than in people with normal magnesium levels. However, incidence rates of sudden death were similar across all magnesium levels. The effect of OM on clinical outcomes was unaffected by magnesium levels."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Omecamtiv mecarbil and red cell distribution width in patients with heart failure and reduced ejection fraction: results from the GALACTIC-HF trial (ESC-WCC 2025) - "RDW, a routinely available and inexpensive biomarker, independently predicts the risk of HF hospitalisation or CV death in HFrEF. In GALACTIC-HF, the benefit of omecamtiv mecarbil was consistent across the range of RDW examined.Figure: Red cell distribution width (RDW) in heart failure. The upper panel illustrates the distribution of RDW, and the lower panel shows the association between RDW and the composite of HF hospitalisation and CV death."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Serum magnesium and outcomes in heart failure with reduced ejection fraction: the GALACTIC-HF trial. (PubMed, Eur Heart J) - "In GALACTIC-HF, 10.7% of outpatients with HFrEF had hypermagnesaemia, which was associated with a higher risk of the primary outcome compared to normal magnesium concentrations. Abnormal magnesium levels were not associated with a higher risk of sudden death or ventricular tachyarrhythmias. These findings do not support routine correction of hypomagnesaemia."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Ventricular Tachycardia

Danicamtiv reduces myosin's working stroke but activates the thin filament by accelerating actomyosin attachment. (PubMed, Proc Natl Acad Sci U S A) - "We demonstrate important mechanistic differences with another cardiac myosin binding myotrope, omecamtiv mecarbil. Finally, we computationally model how the observed changes in mechanics and kinetics at the level of single crossbridges can contribute to increased cardiac contraction. Taken together, our results have important implications for the design of sarcomeric-targeting compounds for heart failure."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Transplantation