Heart failure drug to progress to Phase II trials

Human heart

Cytokinetics has announced topline data from the Phase I study of cardiac myosin inhibitor CK-4021586 (CK-586), which met its primary and secondary objectives.  

The data support the advancement of CK-586 to a Phase II clinical trial in patients with heart failure with preserved ejection fraction (HFpEF) which is expected to begin in Q4 2024. 

“These data reinforce the potential of CK-586 as a drug candidate designed to directly impact the underlying hypercontractility in a subset of patients with HFpEF,” said Fady Malik, Cytokinetics’ Executive Vice President, Research and Development. “Based on previously reported positive Phase II results of aficamten in patients with non-obstructive hypertrophic cardiomyopathy (HCM), we are confident in this approach in HFpEF as the conditions have a similar profile.” 

The primary objective of the Phase I clinical study was to evaluate the safety, tolerability and PK of CK-586 when administered orally as single or multiple doses to healthy participants.  

The study design included seven single ascending dose cohorts (10 mg to 600 mg) comprised of 10 participants each, and two multiple-dose ascending cohorts (100 and 200 mg once daily) comprised of 10 participants each. No serious adverse events were observed, and the stopping criteria were not met in the study. 

CK-4021586 (CK-586) is designed to reduce the hypercontractility associated with heart failure with preserved ejection fraction (HFpEF). In preclinical models, CK-586 reduced cardiac hypercontractility by decreasing the number of active myosin cross-bridges during cardiac contraction, thereby reducing the contractile force, without effect on calcium transients.  

Phase III results for aficamten 

HFpEF can resemble non-obstructive HCM. Aficamten is a cardiac myosin inhibitor also developed by the company to treat non-obstructive HCM. Previous positive Phase II data for the drug has now been supported by data from a Phase III trial presented at Heart Failure 2024, an International Congress of the European Society of Cardiology. 

The results from the SEQUOIA-HCM trial showed that treatment with aficamten for 24 weeks significantly improved exercise capacity compared to placebo. The drug increased peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by 1.8ml/kg/min compared to baseline in patients treated with aficamten versus 0.0ml/kg/min in patients treated with placebo. 

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