Effects of the Novel Long-Acting Amylin Analogue Petrelintide on Body Weight and Waist Circumference by Sex in a Phase 1 Trial

Introduction and Objective: Treatment with GLP1-RAs results in greater weight loss in women. A phase 1 trial investigated treatment with OW s.c. petrelintide; effects by sex were explored post hoc. Methods: Healthy participants (N=48) with overweight/obesity (79% men, median age 49 yrs, BMI 29 kg/m2, body weight (BW) 92 kg, waist circumference (WC) 102 cm) were randomized 3:1 to petrelintide or placebo within three cohorts and treated for 16 weeks. After up-titration, target doses of 2.4, 4.8 and 9.0 mg were administered for 12, 8 and 6 weeks, respectively. AEs, BW and WC were reported in all participants and in petrelintide treated men and women. The pooled placebo group included only 2 women. Results: At 16 weeks, mean BW decreased by 4.8, 8.6 and 8.3% and WC by 5.0, 7.2 and 7.6 cm with the three petrelintide doses versus 1.7% (BW) and 1.9 cm (WC) for pooled placebo. The incidence of gastrointestinal (GI) AEs was low with only one treatment discontinuation due to GI AEs. Vomiting was reported only in this one participant. A consistently greater treatment response was observed in women across the three cohorts (table), whereas incidence of GI AEs appeared similar. Conclusion: Petrelintide treatment resulted in clinically relevant reductions in BW and WC; women appeared to respond better, with a retained favorable tolerability profile. A phase 2 obesity trial with petrelintide is ongoing. Disclosure: D. Hesse: Employee; Zealand Pharma A/S. M.B. Olsen: Employee; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Novo Nordisk A/S. J. Griffin: Employee; Zealand Pharma A/S. U. Hövelmann: None. S. Macura: None. T. Johansen: Employee; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S. B.F. Hagen: Employee; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Novo Nordisk A/S. H. Frimer-Larsen: Employee; Zealand Pharma A/S. Stock/Shareholder; Novo Nordisk A/S. T. Heise: Research Support; ADOCIA, Afon Technology, AstraZeneca, Altimmune Inc, Biocon, BIOTON, Civica Foundation, Eli Lilly and Company, Zealand Pharma A/S, Betagenon, Cass Pharmaceuticals, Novo Nordisk A/S, Corteria, Zealand Pharma A/S, Cytoki, Enyo Pharma, Gan & Lee Pharmaceuticals, Genova, Nanexa, Neodyne, SamChunDang Pharma. Co., Spiden, Sun Pharmaceutical Industries Ltd. Speaker's Bureau; Eli Lilly and Company, Novo Nordisk A/S. Consultant; Gan & Lee Pharmaceuticals. Funding: Zealand Pharma A/S