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| Turkish Society of Cardiology Young Cardiologists Bulletin Year: 7 Number: 1 / 2024 |
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Name of the Study: Safety and Efficacy of Metabolic Modulation With Ninerafaxstat in Patients With Nonobstructive Hypertrophic Cardiomyopathy Published in Congress: ACC 2024 Link: J Am Coll Cardiol.?Apr 08, 2024.?Epublished DOI: 10.1016/j.jacc.2024.03.387 Objective: In nonobstructive hypertrophic cardiomyopathy (nHCM), there are no approved medical therapies. Impaired myocardial energetics is a potential cause of symptoms and exercise limitation. Ninerafaxstat, a novel cardiac mitotrope, enhances cardiac energetics. To evaluate the safety and efficacy of ninerafaxstat in nHCM. Methods:Patients with HCM and left ventricular (LV) outflow gradient <30 mmHg, ejection fraction ?50% and peak VO2 <80% predicted, were randomized to ninerafaxstat 200 mg BID or placebo (1:1) for 12 weeks. Primary endpoint was safety and tolerability with efficacy outcomes also assessed as secondary endpoints. Results :A total of 67 patients with nHCM were enrolled at 12 centers (57 yrs ± 11.8; 55% women). Serious adverse events occurred in 11.8% (4/34) in the ninerafaxstat group and 6.1% of patients (2/33) in placebo. From baseline to 12 weeks, ninerafaxstat was associated with significantly better ventilatory efficiency (VE/VCO2?slope) compared to placebo with a least square (LS) mean difference between the groups of -2.1 (95% CI, -3.4, -0.6; p=0.006), with no significant difference in pVO2?(p=0.9). KCCQ-CCS was directionally though not significantly improved with ninerafaxstat vs. placebo (LS mean, 3.2 [95% CI, -2.9, 9.2; p=0.2]), though was statistically significant when analyzed post-hoc in the 35 patients with baseline KCCQ-CSS ?80 (LS mean, 9.4 [95% CI, 0.2, 18.5; p=0.04]). Conclusions :In symptomatic nHCM, novel drug therapy targeting myocardial energetics was safe and well tolerated and associated with better exercise performance and health status among those most symptomatically limited. The findings support assessing ninerafaxstat in a Phase 3 study. Interpretations :After new drugs such as mavacamten and aficamten introduced in Obstructive Hypertrophic Cardiomyopathy in the past years, this year we are faced with a new agent in Nonobstructive Hypertrophic Cardiomyopathy (nHCM). The fact that the drug is effective in nHCM, although not as much as we expected, seems to have attracted curiosity in terms of its long-term effectiveness on diastolic heart failure.
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