Ninerafaxstat: For the Treatment of Life-Altering Cardiometabolic Disorders
Ninerafaxstat is designed to enhance cellular energy metabolism by increasing the amount of energy produced per molecule of oxygen consumed.
Ninerafaxstat development status
Phase 2 clinical trials have been completed in non-obstructive hypertrophic cardiomyopathy (nHCM), stable angina, and early-stage heart failure with preserved ejection fraction (pre-HFpEF). In Phase 1 and 2 clinical trials, ninerafaxstat was shown to be safe and well tolerated.
Ninerafaxstat mechanism of action
Ninerafaxstat is a novel, investigational cardiac mitotrope in development for the treatment of cardiovascular disease. As a partial fatty acid oxidation (pFOX) inhibitor, ninerafaxstat is designed to shift myocardial substrate utilization in favor of glucose oxidation to generate more ATP per unit of oxygen consumed thereby increasing myocardial metabolic efficiency.
Non-obstructive hypertrophic cardiomyopathy
IMPROVE-HCM Phase 2 Clinical Trial
IMPROVE-HCM (NCT04826185) is a randomized, double-blind, placebo-controlled clinical trial investigating the safety and efficacy of ninerafaxstat 200 mg BID dosed for 12 weeks in 67 patients with nHCM. The primary objective of the study was to evaluate the safety and tolerability of ninerafaxstat in patients with symptomatic nHCM and objective evidence of exercise limitation through evaluation of incidence and severity of treatment emergent adverse events. Efficacy evaluations included exercise responses measured by standardized cardiopulmonary exercise testing and patient-reported symptoms.
Heart failure with preserved ejection fraction
IMPROVE-DiCE Phase 2 Clinical Trial: Part 1: Cardiac Energetics in Patients with Type 2 Diabetes and early stage heart failure (pre-HFpEF), Part 2: Cardiac energetics, function and symptoms in patients with Type 2 Diabetes and HFpEF.
IMPROVE-DiCE (NCT04826159) is the first clinical trial utilizing multi-nuclear and state-of-the-art hyperpolarized MR spectroscopy to quantify the metabolic and energetic responses to an investigational metabolic modulator in cardiovascular disease. It is a two-part, Phase 2 clinical trial evaluating the safety, tolerability and pharmacodynamic effects of ninerafaxstat.
Part 1 enrolled pre-HFpEF patients with type 2 diabetes and obesity and demonstrated normalization of cardiac energetics, significant reduction in cardiac steatosis and improvements to the rate of diastolic filling, an important component of heart failure. The results of Part 1 were presented at the European Society of Cardiology Congress in August 2022.
Part 2 of IMPROVE-DiCE enrolls symptomatic patients with cardiometabolic HFpEF and will assess the impact of ninerafaxstat on cardiac energetics, diastolic function, functional capacity and heart failure symptoms.
The trial is being conducted at the Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Radcliffe Department of Medicine at the University of Oxford, UK and is being led by Professor Oliver Rider.
IMPROVE-ISCHEMIA Phase 2 Clinical Trial: Obstructive Coronary Artery Disease
IMPROVE-ISCHEMIA (NCT04826172) is a randomized, double-blind, placebo-controlled clinical trial evaluating the safety, tolerability of ninerafaxstat in patients with stable angina and chronic coronary syndrome treated for 8 weeks on top of current anti-anginals. The trial further evaluated the anti-ischemic effects of ninerafaxstat through assessment of myocardial blood flow and myocardial functional response to ischemia using dobutamine stress echocardiography.
Please refer to www.clinicaltrials.gov for additional clinical trial information.