Interim Results from ACCESS Program of Aleniglipron Shows Weight Loss Efficacy

On March 16, 2026, Structure Therapeutics reported positive topline results from the ACCESS clinical program, investigating aleniglipron for patients with obesity or overweight and ≥1 weight-related comorbidity.1

The ACCESS program includes 44-week data from the phase 2 ACCESS II study and interim data from an ongoing body composition study, as well as the ACCESS open-label extension study. The former was a randomized, double-blind, placebo-controlled study investigating the safety and tolerability of increasing optimal doses of aleniglipron in patients with obesity or overweight with ≥1 weight-related comorbidity.1,2

“The totality of efficacy and tolerability data across the Phase 2 program continue to demonstrate clear differentiation of aleniglipron, with the highest weight loss observed for an oral GLP-1RA to date and a safety profile appropriate for chronic use in a disease that impacts millions of people,” Raymond Stevens, PhD, chief executive officer of Structure Therapeutics, said in a statement. “The consistent weight loss observed across multiple studies to date reaffirms aleniglipron’s potential to be a best-in-class oral GLP-1, with injectable-like efficacy that could become a backbone oral small molecule therapy for obesity.”1

Aleniglipron is an investigational, oral, once-daily small-molecule GLP-1 receptor agonist designed as a biased G Protein-Coupled Receptor (GPCR) agonist, which selectively activates the G-protein signaling pathway. The drug has demonstrated a consistent tolerability profile with the GLP-1 RA class, as well as a solid safety profile with no off-target events.1

In ACCESS II, patients were eligible for inclusion if they had a body mass index (BMI) ≥30 kg/m2, or a BMI ≥27 kg/m2 and previous or current diagnosis of ≥1 obesity-related comorbidity. Patients were excluded if they had a previous diagnosis of diabetes mellitus, a self-reported change in body weight >5% within 3 months before screening, a prior or planned surgical treatment for obesity, or were using medications intended to promote weight loss within 6 months prior to screening.2

A total of 85 patients were enrolled in the ACCESS II trial and were assigned evenly to aleniglipron or placebo, starting at 5 mg and titrating up to 120 mg, 180 mg, and 240 mg over 4 weeks. By 44 weeks, patients receiving 120 mg of aleniglipron saw a mean body weight change of -13.6%, while the 180 mg arm saw -15.3% and the 240 mg arm saw -15%, compared to +1.1% in placebo (P <.0001). Additionally, the most common adverse events were gastrointestinal-related, with the 2 most common being nausea and vomiting.1

The ACCESS open-label extension is an ongoing investigation following the 36-week phase 2b ACCESS study, after which patients were given the option to continue into the extension and receive aleniglipron for another 36 weeks. Patients were then titrated up to a maximum dose of 120mg during the extension, achieving weight loss ≤16.2% from baseline to 56 weeks.1

The body composition study, an ongoing randomized, placebo-controlled body composition study including 71 patients, aimed to assess the effect of aleniglipron ≤120 mg on body fat loss over a 40-week evaluation period. Participants start at a 2.5 mg dose and titrate monthly to a target dose of 120 mg. After 20 weeks, investigators conducted an interim analysis, highlighting that beginning at a lower dose for the first 4 weeks showed a manageable tolerability profile and 6.8% weight loss.1

“The weight-lowering data from these ACCESS studies, without apparent plateau by Week 56, are encouraging—particularly the weight loss from baseline of up to -15.3% vs +1.1% at 180mg in ACCESS II that hopefully will be confirmed in larger, longer-term studies,” Julio Rosenstock, MD, chair of the ACCESS program Steering Committee and clinical professor of medicine at the University of Texas, Southwestern Medical Center, said in a statement. “In addition, the tolerability profile of starting at a low dose of 2.5 mg and the slow titration positions the program ready for Phase 3 studies.”1

References

1. Structure Therapeutics. 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. Accessed March 16, 2026. https://ir.structuretx.com/news-releases/news-release-details/structure-therapeutics-reports-positive-topline-data-phase-2

2. Gasherbrum Bio. 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 Identifier: NCT06703021. Updated September 15, 2025. Accessed March 16, 2026. https://clinicaltrials.gov/study/NCT06703021