2598-P: Long-Acting Amylin Analog Petrelintide Does Not Delay Gastric Emptying

Introduction and Objective: Native amylin, pramlintide (a short-acting amylin analog) and GLP1 based medications have been shown to delay gastric emptying (GE). We assessed the effect of petrelintide, a long-acting amylin analog in development for weight management, on GE in two clinical trials (NCT05096598, NCT05613387). Methods: GE was assessed using mixed meal tests combined with 1 g acetaminophen after a single dose (SD) of 0.7 - 2.4 mg petrelintide versus placebo (6:2 randomization) in 24 healthy participants (BMI 21-29.9 kg/m2) and after multiple once-weekly (OW) doses (2.4 - 9.0 mg, 3:1 randomization) in 48 healthy participants (BMI 27-39.9 kg/m2) over 16 weeks. Acetaminophen AUC and Cmax were assessed at baseline (prior to the first dose), after the first and/or the sixteenth dose. Results: Petrelintide did not affect GE after SD (Figure 1) or at steady state with OW doses up to 9.0 mg. The incidence of gastrointestinal (GI) AEs was low with OW doses; vomiting occurred in one participant, who was also the only participant to discontinue due to GI AE. After 16 weeks of dosing, mean body weight reductions were up to 8.6%, versus 1.7% for pooled placebo. Conclusion: Petrelintide does not impact GE either after SD or at steady state in doses up to 9.0 mg. Absence of delayed GE and favorable tolerability profile observed in the phase 1 trials potentially represent a clinically relevant benefit of petrelintide. Phase 2 dose finding trial for weight management is ongoing. Disclosure J. Griffin: Employee; Current; Zealand Pharma A/S. M.B. Olsen: Employee; Current; Zealand Pharma A/S. Stock/Shareholder; Current; Zealand Pharma A/S, Novo Nordisk A/S. I.H. Andersen: Employee; Current; Zealand Pharma A/S. Employee; Ended; Novo Nordisk. L. Larsen: Employee; Current; Zealand Pharma A/S. D. Hesse: Employee; Current; Zealand Pharma A/S. U. Hövelmann: None. T. Heise: Research Support; Ended; Afon Technology. Research Support; Current; Betagenon AB, Civica, Corteria Pharmaceuticals. Research Support; Ended; Cytoki Pharma. Research Support; Current; DioGenX, ENYO Pharma, Gan Current; Gan Current; Nanexa, Neodyne Biosciences, Sam Chun Dang. Research Support; Ended; Liom. Research Support; Current; Sun Pharmaceutical Industries Ltd., Zealand Pharma A/S. Other - Travel Grants; Current; Zealand Pharma A/S. Research Support; Current; AstraZeneca, Biocon, Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Research Support; Current; Novo Nordisk, Roche Diagnostics. Consultant; Current; i2o Therapeutics. Speaker's Bureau; Current; Novo Nordisk. Funding Zealand Pharma A/S sponsored study