Ascletis announces mid-phase data for its oral GLP-1 candidate

Ascletis Pharma announced today that the highest dose (60 mg) of its oral GLP-1 candidate achieved significant weight loss and demonstrated improved gastrointestinal tolerability in a phase 2 trial.

The Chinese company's investigational once-daily GLP-1 receptor agonist, named ASC30, delivered up to 7.7% placebo-adjusted weight loss over 13 weeks in a 125-patient U.S. study of adults with obesity or overweight and at least one weight-related comorbidity.

Ascletis tested three dosing levels, with all showing statistically significant results. The participants taking 20, 40 and 60 mg lost 5.4%, 7% and 7.7% more weight, respectively, than those given a placebo.

Reductions in weight had not yet plateaued by the end of the study, the company said.

Although the trial's short duration and smaller scale limit direct comparisons to other oral GLP-1 contenders, the data puts Ascletis' pill in the lower tier of a wave of oral obesity readouts announced this year, including a mid-phase readout for aleniglipron, also announced today.

Aleniglipron, Structure Therapeutics' oral GLP-1 drug candidate, shows the most promise with a 15.3% placebo-adjusted weight loss at the highest testing dose (240 mg) after 36 weeks.

But on track to become the first oral GLP-1 receptor agonist approved for treating obesity is Novo Nordisk's oral version of its blockbuster weight loss drug Wegovy, which is currently under FDA review. The highest dose of the oral formulation (50 mg) demonstrated a 12.7% placebo-adjusted weight loss in a phase 3 trial, following a 68-week testing period.

The FDA is expected to make an approval decision before the year ends.

Novo's oral amylin/GLP-1 co-agonist, amycretin, also showed positive weight loss results last month in a phase 2 readout, with the highest dose (50 mg) reaching a placebo-adjusted weight loss of 7.6% after 36 weeks.

Earlier this year, Viking Therapeutics reported that its oral GLP-1/GIP candidate, VK2735, resulted in 10.9% placebo-adjusted weight loss in patients with obesity after 13 weeks in a mid-stage study. But a fifth of the trial participants who got the drug stopped treatment due to adverse events, with more than a third discontinuing the treatment at the highest and most effective dose (120 mg).

Eli Lilly's closest oral GLP-1 rival, orforglipron, helped people lose 8.3% more weight than a placebo at the highest dose (36 mg) tested in a 72-week phase 3 clinical study. However, Lilly's drug also caused gastrointestinal adverse events that lasted longer than the initial dose–titration phase, an outcome not seen in people taking peptide-based GLP-1s.

When the trial patients increased their dose of ASC30 each week, Ascletis says the vomiting rate was about half of what had been seen with orforglipron.

All stomach-related side effects were mild or moderate and mostly happened while the dose was being increased. Notably, there were no severe side effects and no serious drug-related problems when using ACS30, the company says.

"We are excited about the results from our phase 2 study, which suggests a potential best-in-class profile of ASC30 for both weight loss and GI tolerability," Jinzi Jason Wu, Ph.D., Founder, Chairman and CEO of Ascletis, said in the press release. "Given the significant improvement in GI tolerability seen with the GLP-1 agonist class when titration is slowed from weekly to every four weeks, we expect the GI tolerability of ASC30 tablets to be further improved in phase 3 studies when titrated every four weeks."

Ascletis plans to submit its data to the FDA and request an end-of-phase 2 meeting with the agency within the first quarter of next year, the company says.

Ascletis' pivot to metabolic disease R&D is now its main strategic focus, following the biotech's retreat from its antiviral, oncology and liver disease programs earlier this year.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.