749-P: Integrated Analysis Supports Cardiovascular Safety and Risk Reduction with Pemvidutide Treatment

Abstract

Introduction and Objective: Pemvidutide is a GLP-1/glucagon dual receptor agonist in development for the treatment of obesity and metabolic dysfunction-associated steatohepatitis. Pemvidutide reduces cardiovascular (CV) disease risk factors (excess adiposity, total and LDL cholesterol, cardio-inflammatory lipids, visceral adipose tissue, liver fat content). In this study, its effects on parameters of CV safety were assessed. Methods: Systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR) and rate pressure product (RPP) were assessed in integrated analyses across 5 clinical trials. In a separate QT study, healthy volunteers receiving single ascending doses (SAD) up to 4.8 mg and multiple ascending doses (MAD) up to 3.0 mg once weekly for 12 weeks underwent continuous ECG recordings, and Friderica-corrected QT intervals (QTcF) were assessed by linear time-matched concentration-QTc analysis. Results: In integrated analyses, reductions in SBP and DBP up to 13.0 mmHg and 6.5 mmHg, respectively, were observed without dose-related or clinically meaningful effects on RPP or HR or imbalances in cardiac adverse events. In QTc analyses, mean (90% CI) predicted placebo-corrected change in QTcF (∆∆QTcF) was <10 ms at all pemvidutide concentrations (Figure 1). Conclusion: Pemvidutide reduces SBP and DBP without clinically meaningful effects on QTc or HR and no imbalances in cardiac adverse events. Disclosure S. Tomah: Employee; Altimmune Inc. Stock/Shareholder; Altimmune Inc. J. James: Consultant; Altimmune Inc. S.K. Browne: Employee; Altimmune Inc. B. Darpo: None. M.S. Roberts: Employee; Altimmune Inc. J.J. Suschak: Employee; Altimmune Inc. L. He: None. J. Yang: Employee; Altimmune Inc. M. Harris: Employee; Altimmune Inc.