1781-P: Harmony: A Head-to-Head Phase 3 Study of HTD1801 vs. Dapagliflozin

Introduction and Objective: T2D management focuses on improving glycemic control and reducing cardiovascular (CV) risk. Dapagliflozin (Dapa) has shown CV and renal benefits. HTD1801, an anti-inflammatory metabolic modulator (AIMM) that activates AMPK and inhibits the NLRP3 inflammasome, also improves cardiometabolic and renal parameters. The HARMONY study evaluated the efficacy and safety of HTD1801 vs Dapa in patients with T2D. Methods: Key entry criteria of this Phase 3 double-blind, active-controlled study: T2D, HbA1c 7.0%-10.5%, FPG ≤250.5 mg/dL, and stable metformin use ≥8 weeks. After a 4-week run-in, patients were randomized 1:1 to HTD1801 1000 mg BID (N=186) or Dapa 10 mg QD (N=181). Metformin remained stable. The primary endpoint was HbA1c change from baseline at Week 24 (non-inferiority margin of 0.4%). Results: At Week 24, HTD1801 produced an HbA1c reduction of -1.12% vs -0.93% for Dapa with a LS mean difference of -0.20% (95% CI, -0.37%, -0.03%; p<0.001), confirming non-inferiority. More patients treated with HTD1801 vs Dapa achieved HbA1c <7%. HTD1801 showed superiority for key lipid parameters and eGFR increased in the overall population with HTD1801 compared to no change with Dapa. Treatment-emergent adverse events occurred in 73.1% (HTD1801) vs 64.1% (Dapa) of patients. Conclusion: HTD1801 provided glycemic control comparable to Dapa, with more pronounced and distinctive effects on CV risk factors and therefore may provide a unique treatment option for patients with T2D. Disclosure L. Ji: None. Z. Cheng: None. H. Cai: None. J. Han: None. L. Lu: None. Q. Li: None. H. Wang: None. Y. Wang: None. J. Ma: None. C. Xu: None. D. Zhou: None. B. Lu: None. Y. Bi: None. Y. Bao: None. Z. Zhou: None. K. Liu: Employee; Current; HighTide Therapeutics Inc. L. MacConell: Employee; Current; HighTide Therapeutics Inc. M. Yu: Employee; Current; HighTide Therapeutics Inc. L. Liu: Employee; Current; HighTide Therapeutics Inc.