Structure Therapeutics reports up to 16.3% placebo-adjusted weight loss with oral GLP-1 agonist aleniglipron in Phase 2 ACCESS II trial, supporting Phase 3 development in obesity.
Written By: Sana Khan, BPharm
Reviewed By: Pharmacally Editorial Team
Structure Therapeutics announced positive topline results from its Phase 2 ACCESS clinical program evaluating aleniglipron, an investigational once-daily oral small-molecule GLP-1 receptor agonist, in adults living with obesity or overweight with at least one weight-related comorbidity.
The update includes 44-week data from the ACCESS II trial (NCT06703021) as well as interim findings from an ongoing body composition study and the ACCESS open-label extension (OLE), showing substantial weight reduction, good tolerability, and no evidence of a weight-loss plateau through up to 56 weeks of treatment.
In the randomized, double-blind, placebo-controlled Phase 2 ACCESS II study, which enrolled 85 adults with obesity or overweight (BMI >25 kg/m²) and at least one weight-related comorbidity, aleniglipron produced statistically significant weight reductions at 44 weeks. Participants receiving the 180 mg dose achieved a placebo-adjusted mean weight loss of 16.3% (about 39 lbs), while those receiving 240 mg achieved a 16.0% reduction (about 37 lbs).
The 120 mg dose produced a 13.6% mean weight loss from baseline, corresponding to a 14.7% placebo-adjusted reduction, while the placebo group experienced a 1.1% weight increase. All dose groups reached statistical significance versus placebo (p<0.0001).
Additional data from the ACCESS open-label extension study (NCT06693843) showed continued weight loss beyond the initial randomized treatment period. Participants previously treated with aleniglipron achieved up to 16.2% weight reduction from baseline at 56 weeks after titration to a maximum dose of 120 mg, with investigators reporting no signs of a weight-loss plateau.
Interim results from the ongoing body composition study (NCT07169942), which evaluates the effect of aleniglipron on body fat reduction, also supported the use of a lower starting dose. In this study, participants began treatment at 2.5 mg with monthly titration up to 120 mg, and after a median follow-up of about 20 weeks demonstrated approximately 6.8% weight loss. The lower starting dose was associated with improved tolerability and fewer treatment discontinuations compared with the earlier 5 mg titration schedule used in ACCESS and ACCESS II.
Across more than 625 participants treated in aleniglipron studies, the therapy demonstrated a safety and tolerability profile consistent with the GLP-1 receptor agonist class. Gastrointestinal events, primarily nausea and vomiting during dose titration, were the most common adverse events. In ACCESS II participants receiving doses of 120 mg or higher between weeks 28 and 44, only one adverse-event related treatment discontinuation (3.7%) was reported. Interim analyses also showed 2% discontinuation in the OLE study and 3.4% in the body composition trial. Investigators reported no cases of drug-induced liver injury, persistent liver enzyme elevations, or QTc prolongation.
Based on these findings, Structure Therapeutics plans to advance aleniglipron into Phase 3 clinical development, with initiation expected in the second half of 2026. The company has scheduled a Type B End-of-Phase 2 meeting with the U.S. Food and Drug Administration in the second quarter of 2026 to finalize the Phase 3 trial design, which is expected to include a 2.5 mg starting dose with titration up to 240 mg.
Aleniglipron (GSBR-1290) is an investigational oral small-molecule agonist of the GLP-1 receptor, a validated target for the treatment of obesity and type 2 diabetes. The drug was designed using Structure Therapeutics’ structure-based discovery platform as a biased GPCR agonist that selectively activates G-protein signaling, with the goal of achieving injectable-like efficacy in a convenient oral therapy for metabolic disease.
Reference
Structure Therapeutics Reports Positive Topline Data from Phase 2 ACCESS II Trial with Once-Daily Oral Small Molecule GLP-1 Receptor Agonist, Aleniglipron, March 16, 2026. https://ir.structuretx.com/news-releases/news-release-details/structure-therapeutics-reports-positive-topline-data-phase-2
A Dose-Range Study of Aleniglipron (GSBR-1290) in Participants Living With Obesity or Overweight With at Least One Weight-related Comorbidity (ACCESS II), ClinicalTrials.gov ID NCT06703021, https://clinicaltrials.gov/study/NCT06703021
A Phase 2b, Dose-range Finding Study of the Efficacy and Safety of Multiple Doses of Aleniglipron (GSBR-1290) in Participants Living with Obesity or Overweight With at Least One Weight-related Comorbidity (ACCESS), ClinicalTrials.gov ID NCT06693843. https://clinicaltrials.gov/study/NCT06693843
Aleniglipron Phase 2 Body Composition Study, ClinicalTrials.gov ID NCT07169942, https://clinicaltrials.gov/study/NCT07169942
About the Writer
Sana Jamil Khan is a B.Pharm graduate with a strong interest in medical writing and scientific communication. Her work focuses on interpreting clinical research, exploring developments in pharmaceutical science, and presenting complex medical information in a clear and accessible manner. She is particularly interested in topics related to human clinical studies, drug safety observations, and emerging therapeutic research.