A phase 2 trial of Ascletis’ oral GLP-1 drug candidate has hit its primary and secondary endpoints, positioning the Chinese biotech to mount a two-front attack on Eli Lilly’s Foundayo.
Investigators randomized 100 people with Type 2 diabetes to receive one of three doses of ASC30, Ascletis’ small-molecule GLP-1 receptor agonist, or placebo. HbA1c, a measure of blood sugar, had fallen by 1.6% to 1.7% over 12 weeks across the three ASC30 doses when adjusted for placebo, from a baseline of 8.3%. This hit the study's primary endpoint, according to Ascletis.
Lilly’s Foundayo set the benchmark for oral small-molecule GLP-1 drugs. In a 68-subject phase 1b trial, Lilly reported Week 12 placebo-adjusted HbA1c declines of up to 1.4%, from a baseline of 8.1%. Ascletis used the efficacy estimand, which evaluates the treatment effect of all randomized eligible participants while adhering to treatment. Lilly didn’t say whether it used the efficacy or treatment estimand.
While the effect on HbA1c looks competitive, weight loss on ASC30 in the diabetes trial compared unfavorably to earlier studies of the drug candidate and to assessments of Foundayo. Placebo-adjusted weight loss at Week 13 ranged from 3.8% to 4.4%. Patients had an average body weight of 93.7 kg at baseline. Weight loss in diabetes trials is typically lower than in obesity studies.
At Week 12 of its own phase 1b diabetes study, Lilly reported weight loss of up to 5.8 kg on Foundayo, compared to a 0.5 kg gain on placebo. Average baseline body weight in the placebo and Foundayo cohorts was 90.3 kg and 88.4 kg, respectively, indicating that patients lost up to 7.1% of their weight, adjusted for the control.
Overweight and obesity are the lead indications for ASC30. Ascletis started two global phase 3 clinical trials in overweight and obesity in August. The smaller of the two pivotal studies is enrolling patients with Type 2 diabetes, while patients with the comorbidity are excluded from the larger trial. Ascletis reported placebo-adjusted weight loss of 7.7% at Week 13 of a phase 2 obesity trial.
The pivotal program could position Ascletis to file for FDA approval in obesity by the end of 2028. The diabetes program is less advanced, although, based on the mid-phase data, the biotech believes it has a best-in-class candidate in the indication.
Tolerability is part of Ascletis’ pitch for best-in-class status. No patients discontinued treatment because of gastrointestinal adverse events in the phase 2 diabetes trial. The biotech expects gastrointestinal tolerability to significantly improve in the phase 3 diabetes program, which will use a slower titration schedule.
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