Ascletis Pharma-B (01672) has announced positive topline results from its U.S. Phase II study evaluating the oral small molecule GLP-1 receptor (GLP-1R) agonist ASC30 for the treatment of type 2 diabetes (T2D).
The Phase II trial was a 13-week U.S. study designed to assess the efficacy, safety, and tolerability of once-daily oral small molecule GLP-1R agonist ASC30 tablets in 100 diabetic subjects. The primary endpoint was the reduction in glycated hemoglobin (HbA1c) from baseline at Week 12; one of the secondary endpoints was the reduction in body weight from baseline at Week 13.
ASC30 (40 mg, 60 mg, and 80 mg) met the primary endpoint and all secondary endpoints, achieving significant HbA1c reductions and weight loss, along with improvements in multiple cardiovascular risk factors. Type 2 diabetes represents the second indication being developed for ASC30 beyond obesity.
Regarding the primary endpoint, compared with placebo, ASC30 achieved statistically significant and clinically meaningful HbA1c reductions in diabetic subjects (p < 0.0001). Based on the efficacy estimand, at Week 12, the placebo-adjusted reductions in HbA1c from baseline (least squares mean) for the 40 mg (n=20), 60 mg (n=29), and 80 mg (n=28) dose groups were 1.7%, 1.6%, and 1.7%, respectively. The mean baseline HbA1c of subjects was 8.3%.
For the secondary endpoint of weight loss, compared with placebo, ASC30 achieved statistically significant and clinically meaningful weight reductions (p = 0.001 to 0.003). Based on the efficacy estimand, at Week 13, the placebo-adjusted reductions in body weight from baseline (least squares mean) for the 40 mg (n=20), 60 mg (n=29), and 80 mg (n=28) dose groups were 4.4%, 3.8%, and 4.0%, respectively, with no plateau observed. The mean baseline body weight of subjects was 93.7 kg.
Despite the rapid titration schedule in the study (once weekly), ASC30 continued to demonstrate favorable gastrointestinal (GI) tolerability. ASC30 titrated weekly up to maintenance doses (40 mg, 60 mg, and 80 mg) demonstrated favorable safety and GI tolerability, with no study discontinuations due to GI adverse events (AEs). The favorable GI tolerability observed in diabetic subjects was consistent with findings from studies conducted in obese or overweight subjects. It is anticipated that in the Phase III diabetes program, when titration is slowed to once every four weeks, GI tolerability will be further significantly improved.
There was only one study discontinuation due to any adverse event (1/80, 1.3%, hiccup). There were no study discontinuations due to adverse events in the placebo group. In this U.S. Phase II diabetes study of ASC30, all drug-related adverse events were only Grade 1 (mild) and Grade 2 (moderate) in severity. No drug-related serious adverse events (SAEs) occurred. The overall safety profile of ASC30 in diabetic subjects was consistent with that observed in another Phase II study conducted in obese or overweight subjects (NCT07002905). No liver safety signals were observed. No elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total bilirubin (TBL) occurred during the treatment period. With respect to all other safety signals, ASC30 demonstrated a favorable safety profile in diabetic subjects.
"These data suggest that ASC30 has the potential to be a best-in-class oral small molecule GLP-1 drug for treating diabetes, just as our U.S. Phase II study in obese or overweight subjects demonstrated its efficacy and tolerability as a best-in-class oral small molecule GLP-1 drug for treating obesity," said Dr. Wu Jinzi, Founder, Chairman of the Board, and Chief Executive Officer of Ascletis. "The combination of significant HbA1c reduction, weight loss, and favorable tolerability further strengthens our confidence in advancing ASC30 as a once-daily oral treatment option for patients with type 2 diabetes."
ASC30 is a small molecule GLP-1R fully biased agonist independently developed by Ascletis. The global Phase III program for ASC30 in obesity includes two pivotal trials (AURORA-1, NCT07743463 and AURORA-2, NCT07743450) being conducted in the United States, Europe, and Canada, currently enrolling approximately 4,600 obese or overweight subjects. Topline data from the global Phase III clinical program for ASC30 in obesity are expected in the third quarter of 2028, with a New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) anticipated by the end of 2028, and a Marketing Authorization Application (MAA) submission to the European Medicines Agency (EMA) expected in early 2029. If approved, ASC30 has the potential to become the second oral small molecule GLP-1 receptor agonist launched in the United States and Europe.
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