Modulating energy metabolism to treat non-obstructive hypertrophic cardiomyopathy? Insights from IMPROVE-HCM
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Published on: August 8, 2022
Alberto Beghini1, Alberto Aimo2,3, Andrew P Ambrosy4,5
1Cardiology, ASST Spedali Civili Di Brescia, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
Insights
Ninerafaxstat showed promising safety and efficacy in non-obstructive hypertrophic cardiomyopathy (nHCM) patients. This cardiac mitotrope represents a potential new therapy for nHCM, addressing a significant unmet need in genetic heart disease management.
Area of Science:
- Cardiology
- Genetics
- Pharmacology
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart disease.
- Obstructive HCM has therapeutic options, but non-obstructive HCM (nHCM) lacks evidence-based treatments.
- nHCM patients experience significant symptoms without targeted therapies.
Purpose of the Study:
- To evaluate the safety and efficacy of ninerafaxstat in patients with nHCM.
- To explore ninerafaxstat's potential as a novel therapeutic agent for nHCM.
- To address the gap in evidence-based treatment options for nHCM.
Main Methods:
- Phase 2, randomized, double-blinded clinical trial (IMPROVE-HCM study).
- Assessed safety as the primary endpoint and efficacy as the secondary endpoint.
- Investigated ninerafaxstat, a cardiac mitotrope enhancing ATP production.
Main Results:
- Ninerafaxstat demonstrated acceptable safety in the nHCM population.
- Preliminary efficacy findings suggest potential benefits for nHCM symptoms and function.
- Results provide a foundation for further investigation in nHCM treatment.
Conclusions:
- Ninerafaxstat is a potential novel therapeutic option for nHCM.
- The study marks a significant step towards evidence-based treatments for nHCM.
- Further research is warranted to confirm efficacy and optimize treatment strategies.
Abstract:
Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease worldwide and may present with or without dynamic left ventricular outflow tract obstruction (LVOTO). Significant advances have been made in the management of obstructive HCM. On the other hand, despite their significant symptomatic burden, patients with non-obstructive HCM (nHCM) (i.e., without LVOTO) still do not have evidence-based therapeutical options. The recent IMPROVE-HCM study, a phase 2 randomized, double-blinded trial, aims to place a first step in filling this gap in knowledge. The study assessed the safety (primary endpoint) and efficacy (secondary endpoint) of ninerafaxstat, a novel cardiac mitotrope drug that increases adenosine triphosphate production. We highlighted the main findings of the trial, contextualizing these results within the larger landscape of completed and ongoing trials in nHCM.
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