HRS-1893 Out-Licensed by Hengrui, Enters Myosin Inhibitor Race with Aficamten & Mavacamten

Following our detailed review of aficamten (CK-274) and its Phase III insights versus mavacamten (Camzyos) covered in our previous analysis, Jiangsu Hengrui Pharmaceuticals has now introduced its selective cardiac myosin ATPase inhibitor, HRS-1893, into the global obstructive hypertrophic cardiomyopathy (oHCM) landscape. While aficamten and mavacamten have set clinical and commercial benchmarks, HRS-1893 represents a China-originated innovation with a strategic international licensing approach.

In September 5, 2025, Hengrui granted Braveheart Bio, Inc. exclusive rights to develop, manufacture, and commercialize HRS-1893 globally, excluding Mainland China, Hong Kong, Macao, and Taiwan. The licensing deal includes $65M upfront ($32.5M cash + $32.5M equity), a near-term milestone of $10M, and potential long-term milestones and royalties totaling $1.088B.

Phase I Clinical Data (ESC 2025)

HRS-1893 Phase I results were presented at the 2025 European Society of Cardiology (ESC) Congress. The trial evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy in patients with symptomatic oHCM.

Key findings:

• Population: Symptomatic oHCM patients with resting LVOT gradient ≥50 mmHg (or ≥30 mmHg with post-Valsalva ≥50 mmHg) and LVEF ≥60%.
• Design: Multiple ascending dose (MAD) study; doses: 60 mg and 80 mg orally twice daily for 14 days. Randomized 6:2 vs placebo.
• Safety: All adverse events were mild; no patients had LVEF <50%; mean LVEF changes <20% from baseline and returned to baseline after treatment.
• PK: Steady-state achieved by Day 8; accumulation ratios 1.30 (Cmax) and 2.04 (AUCtau).
• Efficacy / PD: Rapid and substantial reductions in LVOT gradient:
  • Resting LVOT-G decreased 91% (71.2 → 6.0 mmHg) by Day 5
  • Valsalva LVOT-G decreased 87.4% (66.6 → 8.0 mmHg) by Day 5
  • All HRS-1893 patients had Valsalva LVOT-G ≤30 mmHg by Day 14
  • N-terminal pro-B-type natriuretic peptide decreased ~60% from baseline
• Conclusion: HRS-1893 demonstrated favorable safety, PK, and hemodynamic efficacy, supporting 60 mg as the initial therapeutic dose and proof-of-concept in oHCM.

Phase III Clinical Development (NCT07021976)

Building on the Phase I proof-of-concept, HRS-1893 has initiated a Phase III trial in symptomatic oHCM patients (NCT07021976). The study evaluates efficacy, safety, and long-term tolerability, with LVOT gradient reduction, NYHA functional improvement, and LVEF monitoring as primary and secondary endpoints. Results are expected to define HRS-1893’s positioning alongside aficamten (CK-274) and mavacamten (Camzyos) in the global myosin inhibitor landscape.

Deal Snapshot

Pipeline Comparison: HRS-1893 vs Aficamten vs Mavacamten

Strategic Implications

• Global Expansion via NewCo: Hengrui leverages Braveheart Bio’s expertise and investor backing (Forbion, OrbiMed) to accelerate international development.
• Risk Sharing and Value Capture: Upfront payments, equity, milestones, and royalties balance near-term cash with long-term potential.
• Portfolio Synergy: HRS-1893 complements Hengrui’s expanding cardiovascular pipeline, including SHR-6934, SHR-4658, and HRS-9057, strengthening its presence in high-value cardiology innovation.
• Competitive Positioning: HRS-1893 is the first China-originated myosin inhibitor to pursue global licensing, differentiating it from aficamten and mavacamten, which are developed directly by their originating companies.

Market Context

Obstructive HCM is a genetic heart disease characterized by left ventricular hypertrophy and hypercontractility, and it is a leading cause of sudden cardiac death in adolescents and athletes. Myosin inhibitors have become Class IB therapy in the 2025 Chinese HCM guidelines. HRS-1893, if successfully developed and commercialized globally, could become a key competitor in the growing myosin inhibitor market.

Sources

• Jiangsu Hengrui Pharmaceuticals Co., Ltd. (2025). Entering into License Agreement for HRS-1893 with Braveheart Bio, Inc.
• ESC Congress 2025. Safety, tolerability, pharmacokinetics and pharmacodynamics of HRS-1893 in patients with obstructive hypertrophic cardiomyopathy: a randomized, double-blind, placebo-controlled phase 1 trial. Presented by L. Kang et al.
• Aficamten (CK-274) Discovery and Phase 3 Insights vs. Mavacamten in Hypertrophic Cardiomyopathy. Retrieved from SinoDrugWatch
• Chuang, C., et al. (2021). Discovery of Aficamten (CK-274), a Next-Generation Cardiac Myosin Inhibitor for the Treatment of Hypertrophic Cardiomyopathy. Journal of Medicinal Chemistry, 64(18), 13020–13035. doi:10.1021/acs.jmedchem.1c01290
• Garcia-Pavia, P., et al. (2025). Aficamten vs Metoprolol for Obstructive Hypertrophic Cardiomyopathy: Results from the MAPLE-HCM Trial. Journal of the American College of Cardiology, 75(6), 678–688. doi:10.1016/j.jacc.2024.11.011
• ClinicalTrials.gov. HRS-1893 in Obstructive Hypertrophic Cardiomyopathy (Phase III, NCT07021976).

Disclaimer: This article is for informational purposes only and does not constitute medical or investment advice. Readers should consult primary literature and official regulatory sources for verification.