Structure公布小分子GLP-1受体激动剂Aleniglipron用于减重的2b期临床最新数据

SAN FRANCISCO, Dec. 08, 2025 (GLOBE NEWSWIRE) -- Structure Therapeutics Inc. (NASDAQ: GPCR), a clinical-stage global biopharmaceutical company developing novel oral small molecule therapeutics for metabolic diseases, with a focus on obesity, today announced positive topline data from the ACCESS clinical program of aleniglipron for the treatment of people living with obesity and/or overweight with at least one weight related co-morbidity. This includes 36-week data from the core Phase 2b ACCESS study and the ongoing exploratory ACCESS II study, and interim data from the ongoing Body Composition study and the ACCESS open label extension (OLE) study. Aleniglipron is an investigational orally-available, once-daily, nonpeptide small molecule agonist of the glucagon-like-peptide-1 (GLP-1) receptor designed to address patient needs and accessibility.

In the core Phase 2b ACCESS study, aleniglipron achieved a clinically meaningful and statistically significant placebo-adjusted mean weight loss of 11.3% (27.3 lbs, p<0.0001) at the 120 mg dose at 36 weeks and across all active arms had a 10.4% adverse event (AE)-related treatment discontinuation rate. In the exploratory ACCESS II study, aleniglipron achieved a placebo-adjusted mean weight loss up to 15.3% (35.5 lbs, p<0.0001) with 240 mg dose at 36 weeks. Aleniglipron demonstrated a tolerability profile consistent with the GLP-1 receptor agonist class, and a compelling off-target safety profile. Together, these positive findings support the advancement of aleniglipron into Phase 3 clinical development.

“The topline results presented today show that aleniglipron is differentiated and delivered clinically meaningful, competitive and dose-dependent weight loss with a safety profile appropriate for chronic use in a disease that impacts millions of people,” said Raymond Stevens, Ph.D., CEO of Structure Therapeutics. “For the higher doses, the observed weight loss data at 36 weeks with no weight loss plateau is potentially best-in-class for oral small molecule GLP1s. Most importantly, these findings provide comprehensive information to move into Phase 3 development and reinforce aleniglipron’s potential to become a backbone oral small molecule therapy for obesity—one that is accessible, scalable, and combinable.”

“The weight-lowering data from these ACCESS studies, without any evidence of a plateau by Week 36, are very encouraging—particularly weight loss of up to 15.3% in ACCESS II that hopefully will be confirmed in larger, longer-term studies,” said Julio Rosenstock, MD, Chair of the ACCESS program Steering Committee and Senior Scientific Advisor of Velocity Clinical Research and Clinical Professor of Medicine, Univ. of Texas, Southwestern Medical Center. “As once-daily oral, non-peptide, small molecule GLP-1 RAs such as aleniglipron become available, they have the potential to transform obesity treatment and broaden access, which could have a profound impact on patients globally.”

“Obesity is a complex, chronic disease, and far too many individuals still face barriers to accessing effective, long-term treatment options,” said Joe Nadglowski, Obesity Action Coalition President and CEO. “A once-daily oral therapy like aleniglipron has the potential to expand treatment options for people living with obesity. The results from the ACCESS programs represent a promising advance in the therapeutic landscape and bring us closer to a future where people living with obesity have multiple, accessible options to address their needs.”  

Phase 2b ACCESS study - Evaluating target doses of up to 120 mg

The core 36-week Phase 2b ACCESS study was a randomized, double-blind, placebo-controlled, Phase 2b dose-range finding clinical study that enrolled 230 adult participants living with obesity (body mass index (BMI) ≥ 30 kg/m2), or overweight (BMI ≥ 27 kg/m2) with at least one weight-related comorbidity. All participants were randomized 3:1 (active:placebo) and started at 5 mg of aleniglipron (or placebo) with a 4-week titration schedule, reaching target doses of 45 mg, 90 mg or 120 mg once-daily.

Each of the three doses in the ACCESS study achieved statistical significance on the primary endpoint and all key secondary endpoints. Primary efficacy estimandi results at 36 weeks are as follows:

At Week 36, key secondary endpoints in the study show that 86% of participants in the aleniglipron 120 mg dose cohort achieved at least 5% weight loss and 70% achieved at least 10% weight loss. In addition, aleniglipron demonstrated clinically meaningful improvements in systolic blood pressure (-6.4 to -7.5 mmHg) and HbA1c (-0.28% to -0.37%).

Aleniglipron demonstrated a tolerability profile consistent with the GLP-1 receptor agonist class following repeated, once-daily dosing of up to 120 mg in the Phase 2b ACCESS study. As expected for the GLP1-RA drug class, the most common AEs were gastrointestinal (GI)-related and the two most common AEs in the titration phase were nausea and vomiting. AEs were generally observed early in treatment. In the Phase 2b ACCESS study, the AE-related treatment discontinuation rate ranged from 7.7% - 13.3% between all doses, with a mean 10.4% across all active arms in the study.

i The primary efficacy estimand represents efficacy had all randomized participants remained on study treatment (with possible dose interruptions and/or dose modifications) for 36 weeks without initiating rescue weight management treatments or surgeries.