Oral GLP-1 Enters Large-Scale Testing: Ascletis Launches 4,600-Participant Global Phase 3 Trials of ASC30

If weight-loss drugs can shift from injections to a once-daily pill, they may lower the barrier to long-term treatment for some patients, but convenience must be supported by sustained efficacy and acceptable side effects. Ascletis Pharma announced that ASC30, an oral small-molecule GLP-1 receptor agonist, has initiated a global Phase 3 clinical program designed to address these questions in large-scale trials involving approximately 4,600 participants.

The program includes AURORA-1 and AURORA-2, two randomized, double-blind, placebo-controlled studies conducted in the United States, Europe, and Canada. The former will enroll adults with obesity or overweight who do not have type 2 diabetes, while the latter will include those with type 2 diabetes. Both studies will provide 72 weeks of treatment and evaluate the weight-loss efficacy, safety, and tolerability of daily maintenance doses of 20, 40, and 60 mg.

The different doses will be gradually escalated over 12, 16, or 20 weeks, respectively, to reduce gastrointestinal discomfort during the initial treatment period. The company expects to announce topline results in the third quarter of 2028. If supported by the data, it plans to submit a new drug application in the United States by the end of that year and apply for marketing authorization in Europe in early 2029. These timelines remain dependent on trial progress and regulatory review.

The primary human evidence supporting ASC30’s advancement into Phase 3 comes from a 125-participant Phase 2 study in the United States. After 13 weeks of treatment, the 20, 40, and 60 mg groups achieved mean placebo-adjusted body-weight reductions of 5.4%, 7.0%, and 7.7%, respectively, and the weight-loss curves had not yet reached a plateau during the study period. All gastrointestinal adverse events were mild or moderate, and no drug-related serious adverse events or liver safety signals were reported.

However, the 13-week study was limited in size and is not sufficient to determine weight maintenance, discontinuation rates, or rarer risks with use lasting one year or longer. The company previously used data from existing studies to compare vomiting rates between ASC30 and orforglipron, another oral small-molecule GLP-1 drug, but this was not a direct randomized comparison. Participant characteristics and dose-escalation methods may also have differed, so a tolerability advantage cannot be established on this basis.

Ascletis also released animal data on a once-daily oral fixed-dose triple combination of GLP-1, GIP, and amylin: after seven days of treatment, non-human primates lost up to 15.2% of their body weight. This finding remains at the preclinical stage, and the magnitude of short-term weight loss in animals cannot be directly extrapolated to efficacy in humans. At this stage, the development with genuine clinical significance remains whether ASC30 can reproduce its early signals in the two Phase 3 studies and establish a long-term benefit-risk profile.