Structure Therapeutics Reports Aleniglipron Phase 2 Data Showing 16.3% Placebo-Adjusted Weight Loss at 44 Weeks
Structure Therapeutics (NASDAQ: GPCR), a San Francisco-based clinical-stage biopharmaceutical company, reported topline data from its Phase 2 ACCESS II trial of aleniglipron, an oral GLP-1 receptor agonist, in adults with obesity or overweight. The aleniglipron Phase 2 results showed placebo-adjusted mean weight loss of 16.3% at the 180 mg dose and 16.0% at the 240 mg dose over 44 weeks, with no evidence of a weight loss plateau. If these findings hold in larger studies, Structure Therapeutics aleniglipron could become the first oral weight loss drug in the GLP-1 class to deliver efficacy in the range typically associated with injectable therapies.
ACCESS II Trial Results: Dose-Response and Efficacy at 44 Weeks
ACCESS II is a randomized, double-blind, placebo-controlled study that enrolled 85 adults with a BMI greater than 25 kg/m² and at least one weight-related comorbidity. Participants were randomized to aleniglipron or placebo, starting at 5 mg once daily and titrating over four weeks to target doses of 120 mg, 180 mg, or 240 mg. The primary efficacy estimand measured mean percent change in body weight from baseline at 44 weeks, assuming all randomized participants remained on treatment without rescue interventions.
The ACCESS II trial results at 44 weeks were as follows: the 120 mg arm achieved a placebo-adjusted mean weight loss of 14.7% (p<0.0001), the 180 mg arm reached 16.3% or approximately 39 lbs (p<0.0001), and the 240 mg arm reached 16.0% or approximately 37 lbs (p<0.0001). The placebo arm gained 1.1% body weight over the same period. The company noted that weight loss curves had not plateaued at 44 weeks, suggesting further reductions may be possible with continued treatment.
The trial was small — 85 participants across four arms — and the primary efficacy estimand models an idealized treatment scenario rather than real-world adherence. The company did not disclose detailed demographic breakdowns, subgroup analyses, or the precise number of participants per arm.
Open-Label Extension and Tolerability With a Lower Starting Dose
Beyond the controlled ACCESS II data, Structure Therapeutics reported interim findings from two additional studies. In the ACCESS open-label extension, participants who had received aleniglipron during the initial 36-week double-blind period continued treatment at up to 120 mg. At a median follow-up of 56 weeks total, aleniglipron weight loss reached 16.2% from baseline, with no plateau. Participants who had been on placebo crossed over to aleniglipron at a lower starting dose of 2.5 mg, titrating monthly to 120 mg.
A separate body composition study enrolled 71 adults on aleniglipron up to 120 mg, also starting at 2.5 mg. After a median follow-up of 20 weeks, participants had lost 6.8% of body weight and were still in the titration phase, at approximately the 30 mg step.
Both the open-label extension and body composition study provided evidence that the 2.5 mg starting dose reduced adverse event-related discontinuations compared to the 5 mg starting dose used in ACCESS and ACCESS II. Discontinuation rates due to adverse events were 2.0% in the open-label extension and 3.4% in the body composition study, compared to 3.7% in ACCESS II among participants on doses of 120 mg or higher between weeks 28 and 44. Across all studies involving more than 625 participants, the company reported no cases of drug-induced liver injury, no persistent liver enzyme elevations, and no QTc prolongation.