Novel GLP-1 Receptor Agonist Demonstrates Promising Results Treating Patients with Obesity

Image Credit: Adobe Stock Images/Maya Kruchancova

Ascletis Pharma announced positive results from its Phase Ia single ascending dose (SAD) study of ASC30, a novel small-molecule oral GLP-1 receptor agonist (RA) for obesity treatment. The study included five dose cohorts (2 mg, 5 mg, 10 mg, 20 mg, and 40 mg) of 40 patients with obesity under fasting conditions, with results demonstrating dose-proportional pharmacokinetics (PK), a long half-life of up to 60 hours, and superior PK properties to other GLP-1 RAs.¹

"We are excited that the results from our Phase Ia SAD trial of ASC30 oral tablet, once daily in patients with obesity demonstrated potential best-in-class characteristics. With superior PK properties observed in the SAD study, we are looking forward to sharing efficacy, safety, and PK data from Phase Ib 28-day multiple ascending dose (MAD) trial of patients with obesity by the end of March this year," said Jinzi Jason Wu, founder, chairman, CEO, Ascletis, in a press release. "As one small molecule, ASC30 potentially offers both once-daily oral and once-monthly subcutaneous injection dosing options."

Ascletis stated that ASC30 was generally well tolerated during the SAD study, with all adverse events (AEs) being mild (grade 1) or moderate (grade 2), including constipation, diarrhea, vomiting, and nausea.

In addition to the SAD results, Ascletis also provided an update from the Phase Ib 28-day MAD trial for ASC30. Consisting of three cohorts, cohort one (2 mg, 5 mg, 10 mg, and 20 mg) has been completed, while cohorts two (2 mg, 10 mg, 20 mg, and 40 mg) and three (5 mg, 15 mg, 30 mg, and 60 mg) are expected to complete by February or March.¹

According to the World Health Organization (WHO), approximately 16% of people over 18 years of age were living with obesity in 2022. Between 1990 and 2022, the global prevalence of obesity more than doubled. WHO statistics also demonstrate that over 390 million children and adolescents between five and 19 years of age were overweight in 2022, a rise from 8% in 1990 to 20%. Additionally, 160 million children in this age group were living with obesity in 2022.²

According to the Centers for Disease Control and Prevention, the prevalence of obesity among adults was 40.3% between August 2021 and August 2023, including 39.2% in men and 41.3% in women. Among age groups, prevalence in adults between 40 and 59 years of age was 46.4%, 35.5% for adults between 20 and 39 years of age, and 38.9% for adults over 60 years of age.³

In 2022, the World Obesity Federation predicted that by 2030, an estimated one billion people will be living with obesity, with the highest numbers coming from low- and middle-income countries (LMICs). This means that numbers from LMICs will more than double and triple compared to 2010.⁴

“It is clear we will not meet the 2025 UN targets to halt the rise of obesity, however we do have reasons to be optimistic. Every year we are increasing our scientific understanding of obesity, more people than ever are demanding action in their communities, and the recent momentum on securing WHO led coordination through a Global Action Plan on obesity means we should remain hopeful. But the missed opportunity of the last decade should be a warning that success will only come if we all work together and invest in implementing and supporting comprehensive actions to prevent, manage and treat obesity throughout the life course,” said Johanna Ralston, CEO, World Obesity Federation, in a press release.

References

1. Ascletis Announces Positive Results from U.S. Phase Ia Single Ascending Dose Study of Small Molecule Oral GLP-1R Agonist ASC30 and Provides Program Update. PR Newswire. January 21, 2025. Accessed January 21, 2025. https://www.prnewswire.com/news-releases/ascletis-announces-positive-results-from-us-phase-ia-single-ascending-dose-study-of-small-molecule-oral-glp-1r-agonist-asc30-and-provides-program-update-302356018.html

2. Obesity and overweight. WHO. Accessed January 21, 2025. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight#:~:text=In%202022%2C%202.5%20billion%20adults%20aged%2018%20years%20and%20older,1990%20to%2020%25%20in%202022.

3. Obesity and Severe Obesity Prevalence in Adults: United States, August 2021–August 2023. CDC. Accessed January 21, 2025. https://www.cdc.gov/nchs/products/databriefs/db508.htm

4. One Billion People Globally Estimated to be Living with Obesity by 2030. World Obesity Federation. Accessed January 21, 2025. https://www.worldobesity.org/news/one-billion-people-globally-estimated-to-be-living-with-obesity-by-2030#:~:text=Johanna%20Ralston%2C%20CEO%20World%20Obesity,obesity%20throughout%20the%20life%20course.%E2%80%9D