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&J, Juvena, Keros Therapeutic, Inc, Mediflix, Metsera, Neurocrine, Novo Nordisk, Penguin Bio, Pfizer, Regeneron, Response Pharmaceutical, Roche, Sanofi, Shionogi, Skye B, Tenvie, TERNS Pharma, Verdiva Bio, Viking Therapeutics, and Zealand Pharma. R. Kushner: Advisory Panel; 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.