2637-P: Safety, Tolerability, and Efficacy of Aleniglipron in Doses up to 240 mg in People Living with Obesity: The Phase 2 ACCESS II Trial

Introduction and Objective: The Phase 2 ACCESS II trial evaluated safety, tolerability and efficacy of doses up to 240 mg of the novel oral small molecule GLP-1 RA aleniglipron in participants living with obesity or overweight and ≥1 weight-related comorbidity. Methods: Participants (n=73) were randomized 5:1 to once-daily aleniglipron titrated up to 120 mg (starting at 5 mg, increased every 4 weeks) or placebo. At week 28, 37 participants that reached 120 mg were re-randomized to receive 120mg, 180 mg or 240 mg (1:1:1) of aleniglipron or placebo. The total trial duration will be 44 weeks; a pre-specified interim analysis at week 36 is reported here. Results: At baseline, participants were 63% female and mean BMI was 39.4 kg/m2. TEAEs were mostly mild or moderate and reflected the expected profile for GLP-1RAs; all TEAE-related discontinuations occurred before re-randomization (Table). No liver toxicity signal was observed. Body weight loss showed no signs of plateau (Figure). Placebo-adjusted mean body-weight reduction (95% CI) was −14.1% (-19.0 to -9.3), −14.4% (-19.1 to -9.6), and −15.3% (-20.1 to -10.4) in the 120, 180, and 240 mg dose arms (Figure). Data through week 44 will be included in the final presentation. Conclusion: The ACCESS II Phase 2 trial results support the safety, tolerability, and efficacy of higher doses of the novel oral small molecule aleniglipron, and continued evaluation in phase 3 registrational trials for people living with obesity. Disclosure I. Lingvay: Consultant; Current; Aadvarak Therapeutics, Abbvie, Alveus Therapeutics, Amgen, Antag Therapeutics, Arrowhead Pharmaceuticals, Astra Zeneca, Baim Institute, Bain Capital, Bayer, Betagenon AB, Bioio Inc., Biomea, Boehringe. Research Support; Current; Novo Nordisk A/S, Dexcom, Inc., Boehringer Ingelheim International GmbH. Consultant; Current; Eli Lilly, Genentech, Janssen/J Current; AbbVie Inc. Consultant; Ended; Altimmune. Advisory Panel; Current; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. Consultant; Current; Eli Lilly and Company, Regeneron Pharmaceuticals Inc., Viking Therapeutics. Advisory Panel; Current; Antag, Weight Watchers, Structure. A. Jastreboff: Other - multi-center trial; Current; Amgen, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Rhythm Pharmaceuticals. Other - scientific advisory board; Current; Amgen, AstraZeneca, Boehringer Ingelheim, Biohaven, Eli Lilly, Metsera, Novo Nordisk, Pfizer, Regeneron, Roche/Genentech, Scholar Rock, Structure Therapeutics, Syntis Bio, WW International, Zealand Ph. Other - academic co-founder; Current; State 4 Therapeutics. L. Gertsik: Research Support; Ended; Structure Therapeutics. M. Liu: Employee; Current; Structure Therapeutics. A.E. Civitarese: None. C. Ju: None. J. Butcher: Employee; Current; Structure Therapeutics. H. Yue: None. A. Barth: Employee; Current; Structure Therapeutics. B. Coll: Stock/Shareholder; Current; AbbVie Inc., Amgen Inc. Other - Employed by Structure Therapeutics and shareholder; Current; Structure Therapeutics.