HighTide Therapeutics, Inc. (2511.HK), a clinical-stage biopharmaceutical company specializing in the development of multifunctional, multi-targeted therapies for chronic liver and metabolic diseases, today announced that two Phase 3 trials (SYMPHONY 1 and SYMPHONY 2) of berberine ursodeoxycholate (HTD1801) in Chinese patients with type 2 diabetes mellitus (T2DM) met their primary endpoints and gated secondary endpoints.

The results of these two Phase 3 clinical trials provide robust evidence that HTD1801 delivers comprehensive benefits for patients with T2DM. Based on these highly positive read-outs, HighTide plans to submit a new drug application (NDA) for HTD1801 as a treatment for T2DM to the Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) later this year.

SYMPHONY 1 (NCT06350890) and SYMPHONY 2 (NCT06353347) are randomized, double-blind, placebo-controlled, Phase 3 clinical trials designed to evaluate the efficacy and safety of HTD1801 in adults with T2DM and inadequate glycemic control despite using diet and exercise (SYMPHONY 1; N=407) or Metformin (SYMPHONY 2; N=549). The primary endpoint in both studies was the change in HbA1c from baseline with HTD1801 compared to placebo after 24 weeks of treatment. Gated secondary endpoints included the percentage of subjects achieving HbA1c <7.0%, change in fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), glutamyl transpeptidase (GGT), and high-sensitivity C-reactive protein (hs-CRP).

The primary endpoint was achieved in both trials, showing a clinically meaningful, consistent glucose-lowering effect of HTD1801

SYMPHONY 1 (HTD1801 as monotherapy): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.3%) was superior to placebo. Further, those with more severe disease had a greater decrease with HTD1801: reduction in HbA1c was -1.5% for those with a baseline HbA1c =8.5%.

SYMPHONY 2 (HTD1801 as an add-on therapy to Metformin): At week 24, the reduction from baseline in HbA1c with HTD1801 (-1.2%) was superior to placebo. Further, those with more severe disease had a more significant decrease with HTD1801: reduction in HbA1c was -1.6% for those with a baseline HbA1c =8.5%.

In both Phase 3 trials, the efficacy on HbA1c reduction in patients treated with HTD1801 was sustained through week 24.

In both trials, gated secondary endpoints were achieved, suggesting multiple advantages of HTD1801 beyond glucose-lowering including improvement in cardiometabolic risk indicators

At week 24, in both studies, the proportion of patients who achieved HbA1c <7.0% was significantly higher in the HTD1801 treatment groups compared to placebo. Improvements in HbA1c with HTD1801 were parallelled with significant improvements in postprandial and fasting plasma glucose compared with placebo. In addition, HTD1801 demonstrated lipid-lowering effects, including significant reductions in low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). Moreover, HTD1801 treatment led to reductions in key inflammatory biomarkers - glutamyl transpeptidase (GGT) and high-sensitivity C-reactive protein (hs-CRP) - both of which are associated with cardiovascular risk in patients with T2DM.

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