Announcement • Mar 30
Hengrui Pharma And Braveheart Bio Announce Positive Phase 2 Results With HRS/BHB-1893 In Obstructive Hypertrophic Cardiomyopathy Hengrui Pharma, and Braveheart Bio announced results from a multi-center, randomized, open-label Phase 2 dose-ranging study evaluating HRS-1893 (also known as BHB-1893), an investigational next-generation cardiac myosin inhibitor, in patients with obstructive hypertrophic cardiomyopathy (oHCM). In the 42 patient study, HRS-1893 treatment resulted in rapid and substantial reductions in left ventricular outflow tract gradient (LVOT-G), an established measure of cardiac obstruction. The multi-center, randomized, open-label Phase 2 dose-ranging study (NCT06516068 [1]) of 42 patients was designed to measure efficacy and safety of BHB/HRS-1893 and to evaluate dose regimen options that could shorten the time to an effective dose. Patients were randomized 1:1:1 to receive oral BHB/HRS-1893 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 the option 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. BHB/HRS-1893 treatment resulted in rapid and substantial reductions in LVOT-G with minimal change in LVEF across dose groups. Range of complete Valsalva LVOT-G response (<30 mmHg) was between 50% and 86% and the range of LVEF decrease was between 1.8% and 2.7%. BHB/HRS-1893 displayed rapid onset of effect, with the average Valsalva LVOT-G below 30 mmHg as early as day 5. The study found 89% of patients 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. BHB/HRS-1893 treatment also demonstrated improvements in key secondary and exploratory measures in Group 2, the dose selected for open-label extension (OLE), including increase in pVO2 of 1.0 mL/kg/min, KCCQ-CSS of 10.5 points, and reduction in NT-proBNP of 88%. All 42 patients enrolled in the OLE part of the study and continued to receive administration of BHB/HRS-1893. At Week 39 of the OLE, the complete Valsalva LVOT-G response rate was 88%. BHB/HRS-1893 was generally well tolerated, and no new safety signals were identified in the 12-week study period. Reported adverse events were mild to moderate in severity, and no adverse events led to treatment interruption or discontinuation. No patients experienced ejection fraction values below 55% during the 12-week study period. Results of the study were highlighted in a late-breaking featured clinical research presentation at the American College of Cardiology's Annual Scientific Session & Expo. HRS-1893 (also known as BHB-1893) is a selective, small-molecule, cardiac myosin inhibitor engineered to improve heart performance in patients with HCM. By modulating cardiac contractility, HRS-1893 aims to address the underlying pathophysiology of HCM while maintaining cardiac output. HRS-1893 has undergone extensive clinical development, including a dose-ranging Phase 2 study in symptomatic oHCM, an ongoing Phase 2 study in nHCM, multiple clinical pharmacology studies including a bridging study in Australia and an ongoing Phase 3 study in oHCM in China (NCT07021976 [2]). Braveheart Bio entered into an exclusive worldwide license agreement with Hengrui Pharma for the development, manufacture and commercialization of HRS-1893, outside of Mainland China, the Hong Kong SAR, the Macao SAR and Taiwan Region. 
