Key Points
- BHB/HRS-1893, a next-generation cardiac myosin inhibitor, produced rapid, deep, and reversible reductions in LVOT gradients in patients with symptomatic obstructive HCM.
- At 12 weeks, a high proportion of patients achieved clinically meaningful gradient reduction, with improvements in functional capacity and biomarkers.
- The therapy was well tolerated, with no serious adverse events or significant reductions in left ventricular ejection fraction (LVEF).
Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic left ventricular outflow tract (LVOT) obstruction, leading to symptoms of dyspnea, exercise intolerance, and reduced quality of life. While cardiac myosin inhibitors (CMIs) have transformed the management of oHCM, current CMIs often require complex titration and close monitoring with repeated echocardiograms, limiting their scalability in routine practice.
At the American College of Cardiology 2026 Scientific Sessions, Dr. Limei Wang, MD, of Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, presented results from a Phase 2 trial evaluating BHB/HRS-1893, a novel small-molecule cardiac myosin inhibitor engineered for rapid onset, simplified dosing, and minimal impact on systolic function.
BHB/HRS-1893 (NCT06516068) is a selective, reversible inhibitor of cardiac myosin ATPase that reduces actin–myosin cross-bridge formation, thereby decreasing hypercontractility and LVOT obstruction. This Phase 2, multi-dose study enrolled adults with symptomatic oHCM (NYHA class II–III) with resting LVOT gradients ≥50 mmHg (or provocable gradients ≥50 mmHg) and preserved LVEF (≥60%). Participants were assigned to one of three dosing regimens (20–60 mg BID, 40–80 mg BID, or 40–120 mg QD) over a 12-week core treatment period, followed by an extension phase. The primary endpoint was change in Valsalva LVOT gradient at 12 weeks. Secondary endpoints included changes in resting LVOT gradient, peak oxygen consumption (pVO₂), Kansas City Cardiomyopathy Questionnaire (KCCQ) score, NT-proBNP levels, and NYHA functional class.
Treatment with BHB/HRS-1893 resulted in rapid and substantial reductions in LVOT gradients, with effects observed as early as Day 2 and sustained throughout the treatment period. Notably, 86% of patients in the 40–60–80 mg BID cohort achieved a Valsalva LVOT gradient <30 mmHg, representing a clinically meaningful hemodynamic response. These hemodynamic improvements were accompanied by consistent gains in functional capacity and symptoms, including increases in peak oxygen uptake, improvements in KCCQ scores, and a substantial proportion of patients achieving at least one NYHA class improvement.
Cardiac biomarker response was also remarkable. NT-proBNP levels declined markedly across all dosing groups, with over 80% of patients achieving normalization of NT-proBNP, suggesting meaningful reductions in cardiac wall stress. Importantly, these benefits were achieved with minimal impact on systolic function, with mean LVEF reductions of only 1.8–2.7% and no patients experiencing LVEF <55% or requiring dose reductions. Additionally, the study demonstrated the potential for a simplified dosing paradigm, with nearly 90% of patients achieving optimal response on 40–60 mg twice daily without the need for complex titration strategies. The safety profile was favorable. Most adverse events were mild or moderate, with no serious adverse events, treatment discontinuations, or deaths reported during the study.
“These findings suggest that BHB/HRS-1893 may offer best-in-class potential across efficacy, safety, and ease of use,” the investigators concluded, highlighting its rapid, reversible effects and simplified dosing strategy. While the results are promising, limitations include the small sample size and short duration of the core treatment phase. Larger Phase 3 trials will be necessary to confirm durability of benefit and long-term safety.