Cytokinetics 
Welcome,         Profile    Billing    Logout  
 7 Products   203 Diseases   7 Products   6 Trials   1256 News 


12345678910111213...1617»
  • ||||||||||  Verquvo (vericiguat) / Bayer, Merck (MSD)
    Review, Journal:  Pharmacological management of heart failure: a patient-centered approach. (Pubmed Central) -  Nov 18, 2024   
    In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.
  • ||||||||||  tirasemtiv (CK-2017357) / Astellas, Cytokinetics
    Clinical, Journal:  Plasma neurofilament analysis in VITALITY-ALS. (Pubmed Central) -  Nov 15, 2024   
    P3
    In this large longitudinal study, baseline NfL concentration correlated with multiple markers of disease progression. The findings suggest Nfs show promise primarily as prognostic markers for pALS, particularly for those with rapid disease progression.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Journal:  Impact of Aficamten on Disease and Symptom Burden in Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. (Pubmed Central) -  Oct 30, 2024   
    P3
    Treatment with aficamten was associated with substantial improvements across a broad range of clinically relevant efficacy measures. These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818).
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Journal:  Effect of Aficamten on Health Status (Pubmed Central) -  Oct 30, 2024   
    P3
    These results underscore the wide-ranging potential of aficamten for treatment of patients with symptomatic oHCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults with oHCM [SEQUOIA-HCM]; NCT05186818). In patients with symptomatic oHCM, treatment with aficamten resulted in markedly improved health
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Journal:  Effect of Aficamten on Cardiac Structure (Pubmed Central) -  Oct 30, 2024   
    P3
    In patients with symptomatic oHCM, treatment with aficamten resulted in markedly improved health The CMR substudy of SEQUOIA-HCM demonstrated that treatment with aficamten relative to placebo for 24
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier, danicamtiv (MYK-491) / BMS
    Journal:  Differential effects of myosin activators on myocardial contractile function in non-failing and failing human hearts. (Pubmed Central) -  Oct 25, 2024   
    Although these effects were less pronounced with DN compared to OM in failing myocardium, DN impaired contractile properties in failing myocardium that were not affected in donor myocardium. Our results indicate that similar to first-generation myosin activators, the DN-induced slowing of cross-bridge kinetics may result in a prolongation of systolic ejection and delayed diastolic relaxation in the heart failure setting.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Journal:  Dynamics of the Pre-Powerstroke Myosin Lever Arm and the Effects of Omecamtiv Mecarbil. (Pubmed Central) -  Oct 16, 2024   
    Finally, we map out the distinct conformations and ligand-protein interactions adopted by OM. These results uncover some structural factors that govern the motor domain-tail orientations and the mechanisms by which OM primes the pre-powerstroke myosin heads.
  • ||||||||||  omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Journal:  Myosin Isoform-Dependent Effect of Omecamtiv Mecarbil on the Regulation of Force Generation in Human Cardiac Muscle. (Pubmed Central) -  Sep 29, 2024   
    Interestingly, in the ventricle, but not in the atrium, OM induced a large dose-dependent Ca2+-independent force development and an increase in basal ATPase that were abolished by the presence of millimolar inorganic phosphate, consistent with the hypothesis that the widely reported Ca2+-sensitising effect of OM may be coupled to a change in the state of the thick filaments that resembles the on-off regulation of thin filaments by Ca2+. The complexity of this scenario may help to understand the disappointing results of clinical trials testing OM as inotropic support in systolic heart failure compared with currently available inotropic drugs that alter the calcium signalling cascade.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Journal:  Echocardiographic Changes With (Pubmed Central) -  Sep 25, 2024   
    The complexity of this scenario may help to understand the disappointing results of clinical trials testing OM as inotropic support in systolic heart failure compared with currently available inotropic drugs that alter the calcium signalling cascade. No abstract available
  • ||||||||||  aficamten (CK-274) / Cytokinetics, Camzyos (mavacamten) / BMS
    Clinical, Review, Journal:  Evolving Strategies for Management of Obstructive Hypertrophic Cardiomyopathy. (Pubmed Central) -  Sep 20, 2024   
    Long-term data in real world populations will be needed to fully assess the safety and efficacy of mavacamten. Importantly, HCM is a complex and heterogeneous disease and not all patients will respond to mavacamten; therefore, careful patient selection and shared decision-making will be necessary in guiding the use of mavacamten in oHCM.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Global Clinical Impact Of Aficamten In Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM (GWCC - Georgia Ballroom 2) -  Sep 18, 2024 - Abstract #HFSA2024HFSA_1088;    
    P3
    Treatment with aficamten was associated with broad clinical benefits in the vast majority of oHCM patients, including complete hemodynamic response with rest outflow gradient <30 mmHg, substantial alleviation of limiting symptoms, improvement in exercise capacity and significant decrease in NT-proBNP. These findings illuminate the clinical impact of aficamten in the treatment of symptomatic oHCM patients, including those eligible for SRT.
  • ||||||||||  ispinesib (SB-715992) / Cytokinetics
    Biomarker, Journal, IO biomarker, Machine learning:  Deciphering breast cancer prognosis: a novel machine learning-driven model for vascular mimicry signature prediction. (Pubmed Central) -  Aug 21, 2024   
    This model marks a significant step forward in the precise evaluation of breast cancer prognosis and therapeutic responses across different patient groups. It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Phase classification, Enrollment change, Trial completion date, Trial primary completion date:  REDWOOD-OLE: Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of Aficamten in Adults With HCM (clinicaltrials.gov) -  Aug 11, 2024   
    P2/3,  N=900, Enrolling by invitation, 
    It heralds the possibility of refining patient outcomes through tailored treatment strategies, accentuating the potential of machine learning in revolutionizing cancer prognosis and management. Phase classification: P2 --> P2/3 | N=600 --> 900 | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028
  • ||||||||||  Verquvo (vericiguat) / Bayer, Merck (MSD), omecamtiv mecarbil (AMG 423) / Amgen, Servier
    Review, Journal:  Beyond quadruple therapy: the potential roles for ivabradine, vericiguat, and omecamtiv mecarbil in the therapeutic armamentarium. (Pubmed Central) -  Aug 7, 2024   
    Phase classification: P2 --> P2/3 | N=600 --> 900 | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2026 --> Mar 2028 Vericiguat could be considered for high-risk patients who have recently experienced worsening heart failure events despite being on quadrable therapy, but they should not have N-terminal pro-B-type natriuretic peptide levels exceeding 8000
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    Journal:  Dosing and Safety Profile of Aficamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Results From SEQUOIA-HCM. (Pubmed Central) -  Aug 6, 2024   
    P3
    Vericiguat could be considered for high-risk patients who have recently experienced worsening heart failure events despite being on quadrable therapy, but they should not have N-terminal pro-B-type natriuretic peptide levels exceeding 8000 A site-based dosing algorithm targeting the lowest effective aficamten dose reduced left ventricular outflow tract gradient with a favorable safety profile throughout SEQUOIA-HCM.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    PK/PD data, Preclinical, Journal:  In Vitro and In Vivo Pharmacokinetic Preclinical Characterization of Aficamten, a Small Molecule Cardiac Myosin Inhibitor. (Pubmed Central) -  Aug 5, 2024   
    CYP phenotyping indicated multiple CYPs (2C8, 2C9, 2D6, and 3A4) contributing to the metabolism of aficamten.Human clearance (1.1?mL/min/kg) and volume of distribution (6.5?L/kg) were predicted using 4-species allometry employing "rule-of-exponents". A predicted 69?hour half-life is consistent with observed half-life in human Phase-1.No CYP-based DDI liability as a precipitant was predicted for aficamten.
  • ||||||||||  aficamten (CK-274) / Cytokinetics
    PK/PD data, Preclinical, Journal:  Pharmacokinetics, Mass Balance, Tissue Distribution, Metabolism, and Excretion of [14C]Aficamten Following Single Oral Dose Administration to Rats. (Pubmed Central) -  Jul 27, 2024   
    Mean cumulative recovery in urine and feces over 168-hours was 8.3% and 90.7%, respectively.In urine and bile, unchanged aficamten was detected at <0.1 and <0.2% of dose, respectively; however, based on total radioactivity excreted in urine (8.0%) and bile (51.7%), approximately 60% of dose was absorbed.[14C]Aficamten was metabolized by hydroxylation with subsequent glucuronidation where the most abundant metabolite recovered in bile was M5 (35.2%), the oxygen-linked glucuronide of hydroxylated aficamten (M1a). The major metabolite detected in feces was a 1,2,4-oxadiazole moiety ring-cleaved metabolite (M18, 35.3%), shown to be formed from the metabolism of M5 in incubations with rat intestinal content solution.
  • ||||||||||  ispinesib (SB-715992) / Cytokinetics, alisertib (MLN8237) / Puma, volasertib (NBL-001) / Oncoheroes, Notable Labs
    Journal:  Resistance to Spindle Inhibitors in Glioblastoma Depends on STAT3 and Therapy Induced Senescence. (Pubmed Central) -  Jun 19, 2024   
    Treating glioblastomas with the spindle inhibitors ispinesib, alisertib, or volasertib creates a subpopulation of therapy induced senescent cells that resist these drugs by relying upon the anti-apoptotic and metabolic effects of activated STAT3. These results support a therapeutic strategy of targeting STAT3-dependent therapy-induced senescence to enhance the efficacy of spindle inhibitors for the treatment of glioblastoma.