Ascletis Pharma’s rapid-fire expansion into obesity drug development has passed another milestone. The Chinese biotech ticked the publication of multiple ascending dose data off its to-do list Wednesday, linking its oral GLP-1 prospect to 6.3% mean body weight loss after 28 days.
Ascletis announced (PDF) its entry into the booming obesity space in September. Back then, the biotech revealed it had started phase 1 studies of daily oral and weekly subcutaneous formulations of its small molecule GLP-1 receptor agonist ASC30. Later, Ascletis lifted the lid on a muscle-preserving weight loss drug candidate, ASC47, that also entered phase 1 last year.
The biotech shared (PDF) phase 1 data on ASC47 in November and published single ascending dose data on oral ASC30 two months later. Now, Ascletis has provided the first look at the effect of the oral GLP-1 prospect on the weight of people with obesity.
Investigators at a site in Utah enrolled 20 patients across the first two cohorts. Sixteen participants took escalating doses of ASC30—2 mg to 20 mg in cohort one and 2 mg to 40 mg in cohort two—and the other four patients received placebo. Patients took each of four doses for seven days, resulting in average daily doses of 9.25 mg and 18 mg, respectively, in cohort one and cohort two.
Weight loss after 28 days was 6.3% in cohort two, or 6.2% adjusting for placebo. The study detected a dose response, with mean weight loss in cohort one hitting 4.3% after 28 days. Ascletis aims to complete dosing of a third arm, which will receive 5 mg to 60 mg, by the end of March. The current dose response data suggest weight loss could be higher in cohort three, but there may also be more side effects.
Ascletis is yet to provide a close look at the safety and tolerability data from the first two cohorts, but the biotech said ASC30 was generally well tolerated. All gastrointestinal-related adverse events were mild or moderate. Ascletis is holding back data on how common the adverse events were for publication at a medical conference. No clinically significant changes in liver enzymes were seen, the biotech said.
The available data suggest ASC30 could be competitive, although differences between trial designs and the small numbers of patients in many of the studies could make comparisons unreliable. Roche linked its oral GLP-1 candidate CT-996 to 6.1% weight loss after 28 days last year, but the pace of dose titration in that trial may explain both the strong efficacy and the troublesome tolerability profile.
Other 28-day weight loss results include 3.9% for Eli Lilly’s orforglipron, 4% for Novo Nordisk’s amycretin and 5.2% for Pfizer’s danuglipron. The efficacy data should improve in longer trials, as Novo found last year when it linked its oral amylin and GLP-1 receptor co-agonist amycretin to 13.1% weight loss after 12 weeks.
Like the big names in obesity, Ascletis is advancing a pipeline that could tackle the condition from several angles. A phase 1 trial of the weekly injectable formulation of ASC30 is scheduled to wrap up this month, according to ClinicalTrials.gov, and multiple studies of muscle-preserving prospect ASC47 are closing in on data.
Ascletis is testing ASC47 in combination with tirzepatide and semaglutide, the active ingredients in Lilly’s Zepbound and Novo’s Wegovy, respectively. But the presence of ASC30 in the pipeline gives Ascletis the building blocks for a wholly owned combination that could drive weight loss while preserving muscle. A who’s who of leading companies are working on rival combinations, some of which are more advanced.