Abstract Body (Do not enter title and authors here): Hypothesis and Purpose: In a completed Phase 1b/2a trial in obese subjects with modest hypertriglyceridemia, DR10624, a first-in-class long-acting triple agonist targeting FGF21R receptor, Glucagon receptor, and GLP-1 receptor, administered weekly (QW) for 12 weeks, significantly reduced triglycerides (TGs) and liver fat. Building on this finding, the Phase 2 trial was conducted to evaluate the safety and efficacy of DR10624 in adult patients with severe hypertriglyceridemia (SHTG).
Study Design and Method: The Phase 2 trial is a 12-week, multicenter, randomized, placebo-controlled, double-blind study (NCT06555640).
Sample Size: N=79.
Population Studied: Adult SHTG patients (mean TG level between 500 mg/dL and 2000 mg/dL).
Intervention: Subjects were randomized in a 3:1 ratio to receive subcutaneous injections of DR10624 (12.5 mg, 25 mg, and 50 mg) or placebo weekly for 12 weeks.
Power Calculations: We had 82.6% statistical power to detect a 40% difference in TG level changes from baseline between the pooled DR10624 dose groups (n = 54) and the placebo group (n = 18), using a two-sided significance level of 0.05.
Primary End Point: Percent changes in TG from baseline at Week 12.
Outcomes: Results showed significant reductions from baseline in median TGs across all DR10624 groups, compared to placebo at Week 12: Placebo (n=20): -8.0%; 12.5 mg QW (n=21): -74.5% (p<0.0001); 25 mg QW (n=17): -66.2% (p<0.001); 50 mg QW (n=21): -68.9% (p<0.0001). Compared to placebo, a significantly higher proportion of patients treated with DR10624 achieved TG levels <500 mg/dL (89.5% vs. 25.0%; p<0.0001) and a ≥50% reduction in TG from baseline (78.5% vs. 5.0%; p<0.0001). DR10624 treatment also resulted in significant improvements compared to placebo in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglyceride-rich lipoprotein cholesterol (TRL-C).
Remarkably, patients treated with DR10624 had significantly greater reductions in liver fat from baseline at Week 12 compared to placebo (-63.5% vs. -8.4%; p<0.0001).
DR10624 was well tolerated in the study. The most common adverse effects were gastrointestinal symptoms and injection site reactions.
Conclusion: DR10624 treatment significantly reduced TGs, atherogenic lipids, and liver fat in patients with STHG. This profound Phase 2 data underscore DR10624’s strong potential as an innovative and promising treatment for SHTG.