765-P: A Single Ascending Dose Study of the Novel GLP-1 Receptor Agonist GL0034 (Utreglutide) in Obese Individuals without Diabetes

Abstract

The novel incretin analogue, GL0034 (GL), has potent agonist activity at glucagon-like peptide 1 (GLP-1RA) receptor. The primary objective of this phase 1 study in people with obesity was to assess the safety and tolerability of single-ascending doses of GL. Healthy individuals (N=24) with BMI ≥30 kg/m2 were randomized (6:2) to increasing doses of subcutaneous GL (1,520, 2,000 and 2,520 μg) or placebo once-weekly during four weeks. GL pharmacokinetics and key exploratory pharmacodynamic parameters (triglyceride, leptin levels and body weight) were assessed (Table). Most common GL-related adverse events were gastrointestinal with dose-dependent nausea, decreased appetite and vomiting. No injection site reactions or any other adverse events were noted. GL maximum concentrations ranged from 227 to 367 ng/mL, and mean half-life ranged from 99 to 118 h. Triglyceride levels were reduced from baseline following treatment with GL 2,000 and 2,520 μg dose at day 8. Decreases in leptin levels were dose-dependent. Reduction in body weight versus baseline reached a maximum of 3.3 kg with the 2,520 μg dose at day 8 and this effect was sustained through day 22 at every GL dose (Table). In conclusion, once-weekly GL demonstrated clinically relevant reductions in body weight in obese individuals and was well tolerated. Disclosure R.Thennati: None. A.Garcia-ocana: Consultant; Sun Pharmaceutical Industries Ltd. G.A.Rutter: Consultant; Sun Pharmaceutical Industries Ltd. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. B.Thorens: Advisory Panel; Sun Pharmaceutical Industries Ltd. T.Vilsbøll: Consultant; AstraZeneca, Boehringer Ingelheim Inc., Gilead Sciences, Inc., Eli Lilly and Company, Mundipharma, Merck & Co., Inc., Novo Nordisk A/S, Sanofi, Sun Pharmaceutical Industries Ltd., Bristol-Myers Squibb Company. V.S.Burade: None. M.Natarajan: None. P.Shahi: None. R.Nagaraja: None. S.T.Panchal: None. S.K.Agrawal: None. B.Jandrain: None. T.Duvauchelle: None.