Hengrui Pharma and Braveheart Bio Report Promising Phase 2 Results for Next-Generation Cardiac Myosin Inhibitor in Obstructive Hypertrophic Cardiomyopathy
核心洞察
HRS-1893, a next-generation cardiac myosin (搜索) inhibitor, demonstrated rapid and substantial reductions in left ventricular outflow tract gradient with up to 86% complete response rates in a 42-patient Phase 2 study.
The investigational therapy showed minimal impact on left ventricular ejection fraction (1.8-2.7% decrease) while achieving target gradient reduction below 30 mmHg as early as day 5.
Results suggest potential for simplified dosing with minimal titration requirements, addressing key limitations of current therapies for obstructive hypertrophic cardiomyopathy (搜索).
Hengrui Pharma and Braveheart Bio (搜索) have announced positive results from a Phase 2 dose-ranging study of HRS-1893 (also known as BHB-1893 (搜索)), an investigational next-generation cardiac myosin (搜索) inhibitor for obstructive hypertrophic cardiomyopathy (搜索) (oHCM). The 42-patient study demonstrated rapid and substantial reductions in left ventricular outflow tract gradient (LVOT-G), with complete gradient response rates of up to 86% and minimal impact on cardiac function.
Study Design and Patient Population
The multi-center, randomized, open-label Phase 2 dose-ranging study (NCT06516068) enrolled 42 patients with oHCM to evaluate the efficacy and safety of HRS-1893 across different dosing regimens. Patients were randomized 1:1:1 to receive oral HRS-1893 at three different dosing schedules: 20 mg twice daily (potentially titrated up to 60 mg; Group 1), 40 mg twice daily (potentially titrated up to 80 mg; Group 2), or 40 mg once-daily (potentially titrated up to 120 mg; Group 3) for 12 weeks.
The study design included options for individual dosage adjustment based on evaluation of left ventricular ejection fraction (LVEF) and Valsalva LVOT-G. The primary endpoint was change in Valsalva LVOT-G from baseline to Week 12, an established measure of cardiac obstruction in oHCM patients.
Efficacy Results
HRS-1893 treatment resulted in rapid and substantial reductions in LVOT-G with minimal change in LVEF across all dose groups. The range of complete Valsalva LVOT-G response (defined as <30 mmHg) was between 50% and 86%, while the range of LVEF decrease was between 1.8% and 2.7%.
The therapy demonstrated rapid onset of effect, with the average Valsalva LVOT-G falling below 30 mmHg as early as day 5 of treatment. Importantly, 89% of patients were well served at a 40 mg or 60 mg twice-daily dose regimen, with minimal to no titration required to achieve the target dose. All patients were titrated to a final dose based solely on gradient reduction below LVOT-G <30 mmHg.
In Group 2, the dose selected for open-label extension (OLE), HRS-1893 treatment demonstrated improvements in key secondary and exploratory measures, including an increase in pVO2 of 1.0 mL/kg/min, KCCQ-CSS of 10.5 points, and reduction in NT-proBNP of 88%.
Long-term Extension Results
All 42 patients enrolled in the OLE portion of the study and continued receiving HRS-1893. At Week 39 of the OLE, the complete Valsalva LVOT-G response rate was maintained at 88%, demonstrating sustained efficacy over an extended treatment period.
Safety Profile
HRS-1893 was generally well tolerated throughout the 12-week study period, with no new safety signals identified. Reported adverse events were mild to moderate in severity, and notably, no adverse events led to treatment interruption or discontinuation. No patients experienced ejection fraction values below 55% during the study period, indicating preservation of cardiac function.
Clinical Significance and Future Development
"The results of this study build on the clinical data observed to date and reinforce BHB/HRS-1893's potential as a highly differentiated treatment option for patients with oHCM," said Sheng Qi, M.D., Executive Director and Head of Cardiovascular, Hengrui Pharma. "We look forward to further clinical development and continued partnership with Braveheart as we aim to deliver improved treatment options for global patients."
Travis Murdoch, M.D., Chief Executive Officer and President of Braveheart Bio (搜索), emphasized the potential clinical impact: "We believe these results are consistent with a best-in-class clinical profile, with the potential to become a novel, promising treatment option for patients with obstructive hypertrophic cardiomyopathy (搜索). The emerging clinical efficacy profile, along with the potential for a highly simplified dosing regimen, may address key limitations of current therapies and unlock adoption by a broad population of patients with urgent needs."
The positive results were highlighted in a late-breaking featured clinical research presentation at the American College of Cardiology's Annual Scientific Session & Expo. Based on these encouraging data, the companies plan to initiate a global pivotal clinical study in 2026, representing a significant step forward in the development of next-generation therapies for oHCM patients.