Hengrui Pharma and Braveheart Bio reported Phase II results for HRS-1893 (BHB-1893), a selective small-molecule cardiac myosin inhibitor, in patients with obstructive hypertrophic cardiomyopathy, the companies said on March 30. The data, from a 42-patient open-label dose-ranging study (NCT06516068), were presented as a late-breaking clinical research session at the American College of Cardiology Annual Scientific Session.
Across three dose groups over 12 weeks, HRS-1893 produced complete Valsalva left ventricular outflow tract gradient (LVOT-G) responses — defined as a reduction below 30 mmHg — in 50% to 86% of patients, according to the companies. Mean LVEF declined between 1.8% and 2.7% across groups, and no patient recorded an ejection fraction below 55% during the core study period. The companies reported that average Valsalva LVOT-G fell below 30 mmHg as early as day 5. In Group 2, the 40 mg twice-daily cohort selected for an open-label extension, peak oxygen uptake increased by 1.0 mL/kg/min, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score improved by 10.5 points, and NT-proBNP declined by 88%. At week 39 of the open-label extension, in which all 42 patients enrolled, the complete LVOT-G response rate was 88%. Adverse events were mild to moderate in severity, and none led to treatment interruption or discontinuation, the companies said. No new safety signals were identified during the 12-week study period.
The trial randomized patients 1:1:1 to oral HRS-1893 at 20 mg twice daily (titrated up to 60 mg), 40 mg twice daily (up to 80 mg), or 40 mg once daily (up to 120 mg), with individual dose adjustments permitted based on LVEF and Valsalva LVOT-G assessments. The primary endpoint was change in Valsalva LVOT-G from baseline to week 12. The companies reported that 89% of patients were managed at 40 mg or 60 mg twice daily with minimal or no titration. The study was open-label, and no placebo arm was included, which limits interpretation of the magnitude of observed changes. Efficacy data from the once-daily group and full between-group comparative analyses were not disclosed in detail. The data are based on 42 patients, and the open-label extension findings remain preliminary.