Vibegron Beta-3 Agonist Heart Failure Treatment
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Solution Overview
Problem
Current treatments for heart failure, particularly heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), have shown limited success, and there is a need for effective therapeutic modalities to address the modulation of adrenergic receptors in heart failure patients.
Innovation Solution
Administration of vibegron, a highly selective beta-3 adrenergic receptor agonist, alone or in combination with beta-1 and beta-2 adrenergic receptor antagonists, to improve cardiac contractility and function in subjects with heart failure, including those with HFpEF and HFrEF.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If beta-3 adrenergic receptor agonists (e.g., mirabegron) are administered to treat heart failure, then cardiac contractility may be improved, but systolic blood pressure and heart rate increase significantly
Solution Approach 1:
The patent changes the key parameter from non-selective beta-3 adrenergic receptor agonism (mirabegron) to highly selective beta-3 adrenergic receptor agonism (vibegron). This parameter change in receptor selectivity allows achieving cardiac contractility improvement while minimizing the adverse effects on systolic blood pressure and heart rate that were observed with mirabegron
Solution Approach 2:
The patent applies local quality by enhancing the selectivity of vibegron for beta-3 adrenergic receptors in cardiac tissue while minimizing activation of other adrenergic receptors. This localized selective action improves cardiac function without the systemic cardiovascular side effects (increased systolic blood pressure and heart rate) associated with less selective agonists like mirabegron
2Reliability
If beta-3 adrenergic receptor agonists are used to treat heart failure with preserved ejection fraction (HFpEF), then some therapeutic benefit may be achieved, but treatment success has been limited
Solution Approach 1:
The patent changes the parameter of receptor selectivity by using vibegron, which has superior beta-3 adrenergic receptor selectivity compared to mirabegron. This parameter change addresses the limited treatment success in HFpEF by providing more targeted and effective beta-3 adrenergic receptor agonism, potentially overcoming the inadequate therapeutic response observed with less selective agonists
3Strength
If beta-3 adrenergic receptor antagonists are administered to increase cardiac contractility, then contractility may improve, but the therapeutic approach has not been sufficiently explored
Solution Approach 1:
The patent inverts the conventional approach by using beta-3 adrenergic receptor agonists (vibegron) instead of antagonists. The background mentions that beta-3 adrenergic receptors have negative inotropic effects, so the patent applies the 'other way round' principle by activating these receptors with highly selective agonists to achieve beneficial cardiac effects, thereby exploring a novel therapeutic direction that had not been sufficiently investigated
Data Source
AI summary
The present disclosure provides methods of treating or preventing heart failure and/or one or more symptoms thereof, the methods comprising administering to a subject in need thereof a therapeutically effective amount of vibegron.