ulacamten (CK-586) / Cytokinetics - LARVOL DELTA

A First-in-Human Study of Ulacamten, a Novel Cardiac Myosin Inhibitor for HFpEF. (PubMed, Clin Pharmacokinet) - P1 | "Ulacamten demonstrated dose-proportional exposure, a predictable PK/PD relationship with respect to LVEF, and good tolerability, supporting its further clinical development."

First-in-human • Journal • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

In vitro and in vivo preclinical pharmacokinetic characterization of ulacamten, a small molecule cardiac myosin inhibitor for the treatment of heart failure with preserved ejection fraction (HFpEF). (PubMed, Xenobiotica) - "Volume of distribution ranged from 4.23 L/kg in dog to 8.89 L/kg in monkey. Oral bioavailability ranged from 12.6% in mouse to 51.4% in monkey.The predominant ulacamten metabolic pathways in vitro included CYP-mediated deformylation (metabolite M1) and hydroxylation of the methyl group of the methylcyclohexyl moiety (metabolite M2).The predicted human pharmacokinetic parameters clearance (CL), steady-state volume of distribution, and half-life were 4.5 mL/min/kg, 5.8 L/kg, and 14.9-hours, respectively, determined from an average of multiple prediction methods.Ulacamten preclinical attributes and predicted human pharmacokinetic parameters allowed for its progression to clinical development."

Journal • PK/PD data • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure

Danicamtiv, a Novel Direct Enhancer of Cardiac Myosin Motor Function, Improves Cardiac Performance and Output in the setting of Myosin Dysfunction: In vitro and In vivo Evidence. (AHA 2025) - "The responses to DANI were assessed under control conditions and in the setting of myosin dysfunction, resulting from either DCM-pathogenic MYH7 mutations (in recombinant cS1), or via pharmacological cardiac myosin inhibition (MYHi: CK-274 or CK-586) in vitro/in vivo. DANI enhanced the ATPase cycling rate of cS1 in wild-type and five DCM MYH7 variants (AC50, WT: 3.8 µM vs. F764L: 3.2µM). Danicamtiv can directly improve the function of cardiac myosin in the setting of (genetic or induced) dysfunction, increasing the number of myosin heads forming productive cross-bridges, thus increasing/restoring force generation and systolic performance in vivo. These observations, if confirmed in humans, could suggest a potential novel mechanism-based targeted therapy for a subset of patients with DCM"

Late-breaking abstract • Preclinical • Cardiomyopathy • Cardiovascular • CNS Disorders • Depression • Psychiatry • MYH7 • TTN

AMBER-HFpEF: Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF (HFSA 2025) - "The development strategy for CK-4021586 represents an important step in the sub-phenotyping of HFpEF and is intended to enable the evaluation of a cardio-specific drug with a mechanism of action targeting the underlying pathophysiology. The AMBER-HFpEF trial is currently open and enrolling participants."

Clinical • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Heart Failure • Pulmonary Disease

A Single and Multiple Ascending Dose Study of CK-4021586 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=102 | Completed | Sponsor: Cytokinetics | Recruiting ➔ Completed

Trial completion

AMBER-HFpEF: Assessment of CK-4021586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Cytokinetics

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

Cytokinetics Announces Start of AMBER-HFpEF, a Phase 2 Clinical Trial of CK-586 in Patients With Symptomatic Heart Failure With Preserved Ejection Fraction (GlobeNewswire) - "Cytokinetics...today announced that AMBER-HFpEF (Assessment of CK-586 in a Multi-Center, Blinded Evaluation of Safety and Tolerability Results in HFpEF) is open to enrollment. AMBER-HFpEF is a Phase 2 randomized, placebo-controlled, double-blind, multi-center, dose-finding clinical trial of CK-4021586 (CK-586) in patients with symptomatic heart failure with preserved ejection fraction (HFpEF) with left ventricular ejection fraction (LVEF) ≥60%. CK-586 is a cardiac myosin inhibitor in development for the potential treatment of a subgroup of with symptomatic HFpEF patients with hypercontractility and ventricular hypertrophy."

Enrollment open • Heart Failure • Hypertrophic Cardiomyopathy

First look at the AMBER-HFpEF trial: CK-586, a myosin inhibitor, vs placebo 3 ascending cohorts Symptomatic, LVEF>/=60%, NT-proBNP >/=300 #CardioTwitter

A Single and Multiple Ascending Dose Study of CK-4021586 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: Cytokinetics | Trial completion date: Mar 2024 ➔ Nov 2024 | Trial primary completion date: Jan 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date

Cardiac myosin inhibitor, CK-586, minimally reduces systolic function and ameliorates obstruction in feline hypertrophic cardiomyopathy. (PubMed, Sci Rep) - "At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting."

Journal • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy • Obstructive Hypertrophic Cardiomyopathy

A Single and Multiple Ascending Dose Study of CK-4021586 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=132 | Recruiting | Sponsor: Cytokinetics

New P1 trial