Structure Therapeutics reports early ACCG-2671 amylin data and 72-week aleniglipron weight-loss results, advancing its oral obesity drug pipeline.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Structure Therapeutics reported first-in-human data for ACCG-2671, an oral, non-peptide small-molecule dual amylin and calcitonin receptor agonist (DACRA), from the single-ascending-dose (SAD) portion of a Phase 1/2a trial.
The study enrolled 31 healthy adults without obesity who received single doses of 1, 2, 5, or 10 mg, or placebo. ACCG-2671 was rapidly absorbed, with a time to maximum plasma concentration of 1 to 1.5 hours. Its terminal half-life was approximately six days, supporting evaluation of both daily and potentially once-weekly dosing.
The pharmacodynamic findings provided early evidence of target engagement. A single 10 mg dose was associated with a mean 3.3% reduction in body weight from baseline by Day 24. The source does not report this figure as placebo-adjusted, so it should be viewed as an exploratory pharmacodynamic signal rather than a controlled efficacy estimate. CTX-1, a biomarker of bone resorption, also fell by approximately 60% on Day 2 across active-dose cohorts.
ACCG-2671 was generally well tolerated, with no serious adverse events, treatment-related adverse events leading to discontinuation, or drug-induced liver injury. No nausea or vomiting occurred in the placebo, 1 mg, or 2 mg cohorts. Gastrointestinal events increased at 5 mg and 10 mg, including nausea and vomiting, findings that informed the starting doses and gradual titration being tested in the next stage of development.
12-Week MAD Study Moves into Obesity
The company has begun dosing the multiple-ascending-dose (MAD) portion of the Phase 1/2a program in people living with obesity. The randomized, placebo-controlled study will evaluate multiple ascending oral doses administered for 84 days across five cohorts.
The trial will compare daily and weekly dosing regimens and assess different titration strategies. One cohort will also evaluate ACCG-2671 in participants receiving a stable injectable GLP-1 receptor agonist, providing an early assessment of combination treatment. Topline MAD data are expected in the first half of 2027.
Aleniglipron Sustains Weight Loss Through 72 Weeks
The company also reported 72-week results from the ACCESS open-label extension (OLE) of aleniglipron, an investigational once-daily oral small-molecule GLP-1 receptor agonist.
Participants originally assigned to 45 mg, 90 mg, or 120 mg in the Phase 2b ACCESS study continued into the OLE and were titrated every four weeks to doses of up to 180 mg. By Week 72, the respective groups achieved 11.6%, 14.4%, and 16.2% weight loss. More than one-third of participants in the 90 mg and 120 mg groups achieved more than 20% body-weight reduction, while the two highest-dose groups showed no evidence of a weight-loss plateau.
Participants did not receive prolonged exposure to the 180 mg dose. The protocol reached the highest dose at approximately Week 60, leaving relatively limited time at 180 mg before the Week 72 assessment. This makes the continued weight reduction at Week 72 notable but also limits interpretation of the 180 mg dose as a full-duration maintenance regimen.
Tolerability improved when treatment began at 2.5 mg rather than 5 mg. Participants who crossed over from placebo at Week 36 started at 2.5 mg and were gradually up-titrated every four weeks, achieving 9.0% weight loss after 36 weeks of treatment. Across the OLE, fewer than 5% of participants discontinued because of treatment-emergent adverse events. No drug-induced liver injury was reported.
Phase 3 Program Targets 2028 Readout
Aleniglipron is now being evaluated in the Phase 3 ACCOMPLISH program. ACCOMPLISH-1 will enroll up to 3,600 adults with obesity or overweight and at least one weight-related comorbidity, while ACCOMPLISH-2 will enroll up to 1,100 adults with obesity or overweight and type 2 diabetes.
Both trials will compare placebo with 45 mg, 90 mg, or 180 mg maintenance doses following a 2.5 mg starting dose and four-week dose escalation. The program will evaluate long-term efficacy and safety and support global regulatory submissions. Topline data are expected in the second half of 2028.
Three Aleniglipron Readouts Expected in Q4 2026
Three additional clinical studies could provide more detail on aleniglipron’s profile in the fourth quarter of 2026.
A 44-week Phase 2 Body Composition study will assess changes in body fat and overall body composition, including DXA-based measurements. A separate Phase 2 study will evaluate aleniglipron in adults with obesity or overweight and type 2 diabetes. The Phase 1 SWITCH study will examine the transition from approved injectable GLP-1 therapy to once-daily oral aleniglipron.
Together, these studies could determine not only how much weight patients lose with aleniglipron, but also the composition of that loss, its performance in people with type 2 diabetes, and its potential role as an oral alternative following injectable GLP-1 treatment.
Reference
Structure Therapeutics Reports Positive Clinical Data Across Oral Small Molecule Amylin and GLP-1 Programs for Chronic Weight Management, Structure Therapeutics, 08 September 2026
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content.