Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic...

Area of Science:

• Cardiology
• Pharmacology
• Biochemistry

Background:

• Nonobstructive hypertrophic cardiomyopathy (nHCM) currently lacks approved medical therapies.
• Impaired myocardial energetics contributes to symptoms and exercise limitations in nHCM.
• Ninerafaxstat is a novel cardiac mitotrope designed to enhance cardiac energetics.

Purpose of the Study:

• To evaluate the safety and efficacy of ninerafaxstat in patients with nHCM.
• To assess the impact of ninerafaxstat on exercise performance and health status.

Main Methods:

• A randomized, placebo-controlled trial involving 67 patients with nHCM.
• Patients received either ninerafaxstat (200 mg twice daily) or placebo for 12 weeks.
• Primary endpoint was safety and tolerability; secondary endpoints included efficacy outcomes like ventilatory efficiency and quality of life.

Main Results:

• Ninerafaxstat demonstrated a significant improvement in ventilatory efficiency (VE/VCO2 slope) compared to placebo (P=0.006).
• No significant difference was observed in peak oxygen consumption (VO2).
• The Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score showed significant improvement in a subgroup of patients with lower baseline scores (P=0.04).

Conclusions:

• Ninerafaxstat is safe and well-tolerated in symptomatic nHCM patients.
• The drug is associated with improved exercise performance and health status, particularly in severely symptomatic individuals.
• Findings support further investigation of ninerafaxstat in a phase 3 clinical trial.