Development

Hengrui, Braveheart's cardiac myosin inhibitor produces positive Phase II data in non-obstructive HCM

Phase 2 data for HRS/BHB-1893 in non-obstructive hypertrophic cardiomyopathy show reductions in cardiac biomarkers and structural remodeling markers, with a...

Phase II data for HRS/BHB-1893 in non-obstructive hypertrophic cardiomyopathy show reductions in cardiac biomarkers and structural remodeling markers, with a tolerability profile that Hengrui Pharma and Braveheart Bio said supports advancement to a registrational study. Results from the randomized, double-blind, placebo-controlled Phase II trial (NCT06816251) in 84 adults with symptomatic non-obstructive HCM (nHCM) were presented at Heart Failure 2026, the annual congress of the Heart Failure Association of the European Society of Cardiology.

In the high-dose group, NT-proBNP fell by 68–69% and cardiac troponin I by 55–60% from baseline, both with p values below 0.0001 versus placebo, according to company-reported data. Echocardiographic findings included a 17.4 g/m² decrease in left ventricular mass index versus a 3.2 g/m² increase in the placebo arm, a 3.3 mm reduction in left ventricular wall thickness versus 0.1 mm in placebo, and a 7.1 mL/m² fall in left atrial volume index with essentially no change on placebo. Septal and lateral e' values, measures of early myocardial relaxation velocity, moved toward normal range in the high-dose cohort. On patient-reported outcomes, the high-dose group showed a placebo-adjusted improvement of +5.5 points in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS); 52% of high-dose patients achieved a ≥20-point improvement, the threshold for a large to very large improvement, compared with 21% in the placebo group. Among patients titrated to 60 mg twice daily, absolute peak oxygen consumption (pVO₂) change was +2.1 mL/kg/min, representing a placebo-adjusted gain of +0.9 mL/kg/min, with 55% of high-dose patients achieving a ≥1.5 mL/kg/min increase from baseline.

The trial enrolled adults with LVEF ≥60%, New York Heart Association Class II–III symptoms, maximal wall thickness ≥15 mm (or ≥13 mm with a family history of HCM), left ventricular outflow tract gradient below 30 mmHg at rest and with provocation, NT-proBNP above 300 pg/mL, and KCCQ-CSS between 30 and 85. Treatment-emergent adverse events were mild or moderate in severity; no severe adverse events occurred, and no events led to temporary interruption or permanent discontinuation of HRS/BHB-1893. Serious adverse events were reported in four patients — two in the low-dose group (cellulitis, otolithiasis), one in the high-dose group (atrial fibrillation in a patient with a prior history of the arrhythmia), and one on placebo (atrial tachycardia) — all assessed as unrelated to study drug. Four patients, representing 7% of those treated, experienced a temporary drop in LVEF with a nadir between 46% and 49% requiring dose reduction; all four returned to an LVEF above 50% following the reduction. The companies said a global registrational study is planned.

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HRS/BHB-1893 is an oral small-molecule cardiac myosin inhibitor designed to modulate cardiac contractility and reduce pathologic hypercontractility in HCM. The nHCM population presents a distinct development challenge relative to obstructive HCM: without a left ventricular outflow tract gradient to relieve, the mechanical confound present in obstructive disease is absent, which the companies argued makes the structural reverse remodeling signal more interpretable as a direct biological effect. The only cardiac myosin inhibitor currently approved by the US FDA for HCM is mavacamten (Camzyos, Bristol Myers Squibb), which holds approval in obstructive HCM; no pharmacological therapy is approved specifically for nHCM. Cross-trial comparisons are limited by differences in study design, duration, and patient populations.


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