Ninerafaxstat
Ninerafaxstat: For the Treatment of Cardiovascular Diseases
Ninerafaxstat is currently in Phase 2 clinical development for multiple cardiovascular diseases, common as well as rare.
Ninerafaxstat is designed to enhance cellular energy metabolism by increasing the amount of energy produced per molecule of oxygen consumed.
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.
Ninerafaxstat development status
Ninerafaxstat is currently being investigated in three Phase 2 proof-of-concept clinical trials in patients with non-obstructive hypertrophic cardiomyopathy, stable angina, and heart failure with preserved ejection fraction (HFpEF). In Phase 1 clinical trials, ninerafaxstat was shown to be safe and well tolerated.
Non-obstructive hypertrophic cardiomyopathy
IMPROVE-HCM Phase 2 clinical trial
IMPROVE-HCM is a randomized, double-blind, placebo-controlled study assessing the safety, tolerability, and efficacy of ninerafaxstat in patients with non-obstructive hypertrophic cardiomyopathy (nHCM). This study will measure the change from baseline of peak oxygen consumption (VO2) and oxygen uptake efficiency slope (OUES), measured by standardized cardiopulmonary exercise testing (CPET) in 60 nHCM patients treated with 200 mg BID of ninerafaxstat over a 12-week period. Incidence and severity of treatment emergent Adverse Events will also be examined.
Please refer to www.clinicaltrials.gov for additional clinical trial information.
Heart failure with preserved ejection fraction
IMPROVE-DiCE Phase 2a Study: 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 heart failure with preserved ejection fraction.
The IMPROVE-DiCE clinical trial, Part 1 is a Phase 2, target engagement study in patients with diabetes, obesity and early stage of heart failure (pre-HFpEF). The primary outcome measures is the change in cardiac PCr/ATP ratio at rest measured by 31P-MRS over an eight-week period, while also examining the safety and tolerability of ninerafaxstat. This part of the study completed end of 2021 and data will be presented at the ESC in August 2022.
Part 2 of the study will assess the effect of ninerafaxstat 200 mg BID in patients with cardiometabolic HFpEF measuring change in cardiac energetics, cardiac function at rest and during exercise, and measures of patient symptoms.
Please refer to www.clinicaltrials.gov for additional clinical trial information.
LEARN MORE ABOUT HEART FAILURE
Stable angina
IMPROVE-ISCHEMIA Phase 2 Study: Obstructive Coronary Artery Disease
IMPROVE-ISCHEMIA is a randomized, double-blind, placebo-controlled, Phase 2 study that will examine the safety and tolerability of ninerafaxstat in patients with obstructive coronary arterial disease (CAD) and inducible ischemia. The study will examine the change in number of ischemic segments during hyperemia (ischemia defined as absolute MBF ≤2.3 ml/kg/min) as measured by adenosine stress 15O-H2O PET in 60 obstructive CAD patients treated with 200 mg BID of ninerafaxstat over an 8-week period. The measure of incidence and severity of treatment emergent Adverse Events will also be examined.
Please refer to www.clinicaltrials.gov for additional clinical trial information.