Ascletis Pharma has posted phase 2 data on its ultra-long-acting GLP-1 receptor analog, generating early evidence that the formulation may support quarterly dosing as a maintenance therapy.
Eli Lilly’s and Novo Nordisk’s approved injectable GLP-1 medicines are given weekly, leading would-be rivals to identifiy the dosing frequency as a potential weakness. Pfizer’s $10 billion takeover of Metsera included a GLP-1 candidate that is initially given weekly before switching to monthly maintenance dosing. Ascletis aims to improve on that regimen, starting patients on monthly dosing before potentially going quarterly.
The Chinese biotech put the idea to the test in a phase 2 trial of a subcutaneous depot formulation of its GLP-1 receptor agonist ASC30. U.S. investigators randomized 65 people with obesity or who were overweight with a comorbidity to receive one of two ASC30 formulations or placebo monthly for three months.
One ASC30 formulation failed to provide therapeutic drug exposures. Patients on the other formulation, A1, had 6.3% placebo-adjusted weight loss at Week 12, one month after receiving their third and final dose. Ascletis said the data suggest ASC30 can be given once monthly—and potentially once every two months—without requiring a weekly lead-in dosing period.
Placebo-adjusted weight loss deepened to 7.5% at Week 16 before falling to 6.4% at Week 20 and 5.8% at Week 24. With patients having near-identical weight loss one and three months after the final dose, the biotech said the drug candidate could be an effective once-quarterly maintenance therapy for obesity.
While the formulation could be more convenient than other drugs, Ascletis’ weight loss results fall short of the bar set by more frequently dosed rivals. After 12 weekly doses, Pfizer’s long-acting therapy drove placebo-adjusted weight loss of up to 11.3% in a phase 2a trial. Another Pfizer trial reported placebo-adjusted weight loss of 12.3% at Week 28 in patients who switched from weekly to monthly doses at Week 12.
Ascletis CEO Jinzi Jason Wu, Ph.D., said in a statement that the latest ASC30 data reinforce his confidence in expanding the clinical development program for once-monthly treatment therapy and once-quarterly maintenance dosing. The biotech made a major pivot to obesity last year, pulling back from its traditional areas of focus to invest in assets including oral and ultra-long-acting injectable formulations of ASC30.
Wu added that the new data validate ultra-long-acting injectable technology that Ascletis is applying to other molecules. In January, the biotech selected a once-monthly GLP-1R/GIPR/GCGR triple agonist for clinical development. Ascletis plans to ask the FDA for clearance to run a clinical trial of the candidate in the second quarter.