770-P: Efficacy and Safety of Once-Weekly PB-119 Monotherapy vs. Placebo in Chinese Patients with Type 2 Diabetes in a Randomized Controlled Trial

Background: PB-119 is a novel once-weekly polyethylene glycolated exenatide developed in China for T2DM treatment. Favorable efficacy and safety profile had been demonstrated in two phase 2 studies respectively completed in US and China. Methods: In this multicenter, double-blind, placebo-controlled, 52-week phase 3 study, 273 drug-naïve Chinese patients with type 2 diabetes were randomized (1:1) to receive subcutaneous PB-119 150ug once weekly or volume-matched placebo once weekly for 24 weeks, followed by 28-week extension during which all the patients were treated with PB-119 150ug once weekly. The primary endpoint was the HbA1c change from baseline to week 24. ClinicalTrials.gov, NCT04504370 Results: At week 24, HbA1c showed a significantly decrease with PB-119 (-1.35%) than placebo (-0.51%, p<0.001). Significant more patients reached the target of HbA1c less than 7.0% in the PB-119 group versus the placebo group (50.4% vs 14.2%; p<0.001). Significant greater reduction in FPG (-1.26mmol/L vs. -0.52mmol/L) and PPG (-2.52 vs. -0.85mmol/L) were achieved (P<0.001). The remarkable glycemic lowering effect sustained till the end of week 52. Meanwhile, Insulin, C-peptide and HOMA-ß were significantly increased with PB-119 versus placebo. HOMA-IR was significantly reduced with PB-119 compared with placebo. Significant improvement of blood pressure and blood lipid profile were demonstrated with PB-119 treatment early from week 8 (TC -0.2mmol/L, LDL-C -0.19mmol/L, DBP -1.8mmHg at week 52, p<0.05 compared to the baseline). Most adverse events were mild and transient. Incidence of nausea (8%) and vomit (5.1%) were low. No Grade 2 or above hypoglycemia (< 3.0mmol/L) occurred. Conclusion: PB-119 significantly and sustainably improves glycemic control, lipid profile, blood pressure, beta-cell function and insulin resistance, and well tolerated. Dose titration is not needed. Disclosure Pegbio study group: n/a. M.Xu: None. R.Liang: None.