Ascletis Pharma has announced positive topline results from a US phase 2, 24-week study for its subcutaneous (SQ) depot formulations of small molecule GLP-1 receptor (GLP-1R) agonist ASC30 for obesity.
All 65 participants enrolled in three cohorts utilising two formulations (A1 and A2) were obese or overweight with at least one weight-related comorbidity.
The phase 2 study achieved its primary endpoint, with patients receiving three doses of once-monthly ASC30 SQ depot formulation A1 demonstrating a statistically significant (p < 0.05 vs placebo) and clinically meaningful placebo-adjusted mean weight loss of 6.3% at week 12. Additionally, ASC30 SQ depot formulation A1 achieved a statistically significant (p < 0.05 vs placebo) and clinically meaningful placebo-adjusted mean weight loss of 7.5% at week 16 after three monthly doses.
The phase 2 study was a randomised, double-blind, placebo-controlled and multi-centre 24-week study conducted in the US to evaluate the safety, tolerability and efficacy in 65 participants with obesity (body mass index (BMI) ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2 but < 30 kg/m2) with at least one weight-related comorbidity.
All 65 participants were given three monthly ASC30 SQ depot doses or matching placebo at day one, day 29 (week four) and day 57 (week eight), without requiring lead-in weekly doses. The maintenance period was 16 weeks, starting from week eight to week 24.
The study evaluated two SQ depot formulations of ASC30 (A1 and A2). The study objective was to evaluate the potential for once-monthly dosing for treatment therapy and once-quarterly dosing for maintenance therapy. ASC30 SQ depot formulation A1 was previously studied in the 12-week Phase Ib single dose study (NCT06679959) and demonstrated an observed half-life of 46 days to 75 days.
No human studies of ASC30 SQ depot formulation A2 were conducted previously. Formulation A1 achieved therapeutic drug exposures in obese patients in this study while formulation A2 did not.
For ASC30 SQ depot formulation A1, all participants were given three SQ doses of 400 mg each with a four-week dosing interval at day one, day 29 (week four) and day 57 (week eight). ASC30 SQ depot formulation A1 achieved placebo-adjusted mean body weight loss of 2.7%, 5.5%, 6.3%, and 7.5% at week four, week eight, week 12 and week 16, respectively.
The data demonstrate that ASC30 SQ depot formulation A1 can be dosed once monthly and potentially once every two months for the treatment of obesity without requiring a weekly lead-in dosing period.
This Phase II study also evaluated the potential for ASC30 SQ depot formulation A1 to be used as a maintenance therapy.
Patients in the study were evaluated for duration of effect for 16 weeks following the final dose on week eight. ASC30 SQ depot formulation A1 achieved therapeutic drug exposures over this 16-week maintenance period after the final dose.
Placebo-adjusted mean weight loss was 5.5% at week 8, 6.4% at week 20 (three months following the final dose), and 5.8% at week 24 (four months following the final dose).
These results demonstrate that ASC30 SQ depot formulation A1 has the potential to be an effective once-quarterly maintenance therapy for obesity.
ASC30 SQ depot formulations A1 and A2 were safe and well tolerated, demonstrating a safety and tolerability profile consistent with the GLP-1 drug class.
There were no discontinuations due to adverse events (AEs) for either ASC30 SQ depot formulations A1 and A2 or placebo-treated participants. All AEs, including injection site AEs, were mild to moderate in severity.
All gastrointestinal (GI) AEs were mild (grade 1) with no moderate (grade 2) or above GI AEs. No hepatic safety signal was observed.
In addition, there were no abnormal findings in laboratory tests, vital signs, ECGs (electrocardiograms, including QTc intervals), and physical exams.
ASC30 was discovered and developed in-house at Ascletis as the first and only investigational small molecule GLP-1R biased agonist designed to be administered once daily orally and once monthly to once quarterly subcutaneously as a treatment therapy and a maintenance therapy for chronic weight management.
