Ascletis is taking a low and slow approach to oral GLP-1 dose titration in a phase 2a test after getting a look at clinical data. The latest results show a high starting dose, fast titration model provides the same weight loss and worse tolerability than more measured approaches.
The new data come from the third cohort of a phase 1b trial of the oral GLP-1 prospect ASC30. Ascletis shared data from the first two cohorts back in February, linking the molecule to up to 6.3% mean body weight loss after 28 days. At the time, Ascletis was still dosing people in a third cohort that began on a 5-mg dose and then ramped up to 60 mg. The first two cohorts began on 2 mg and moved up to either 20 mg or 40 mg.
Ascletis reported data from the seven patients in the third cohort on Tuesday evening. Mean weight loss after 28 days was 4.8%. The result was dragged down by two outliers who lost 1.8% of their weight, the biotech said. The first two cohorts were free from such outliers.
Placebo-adjusted weight loss was 6.1% after removing the outliers from the third cohort, compared to 6.5% for the second cohort. Maximum body weight reduction in the second and third cohorts, 9.1% and 9.3%, respectively, was comparable, too. The decision to drop the high starting dose, fast titration model was sealed by gastrointestinal tolerability data.
Ascletis saw no grade 3 or higher adverse events across the three cohorts, but safety and tolerability were worst with the start high, titrate quickly dosing model. Across the first two cohorts, the biotech said most gastrointestinal-related adverse events were grade 1 and short-lived. Ascletis is yet to share full data but said gastrointestinal tolerability in the first two arms was similar or better than for rival assets.
The biotech cited Eli Lilly’s oral hopeful orforglipron by name. Lilly cemented its credentials as a front-runner for the oral GLP-1 race last week by publishing phase 3 data in people with diabetes. Novo Nordisk is, however, currently in the lead, having recently filed for FDA approval, but Lilly is following close behind. Lilly plans to post phase 3 data in obesity and file for approval of orforglipron in the indication this year.
Lilly and Novo both already have approved injected weight loss meds in the forms of Zepbound and Wegovy, respectively, but an oral version of these types of anti-obesity treatments would prove an easier route of administration, and thus a next-gen approach in what is already shaping up to be a megablockbuster market.
Ascletis has submitted a protocol for a phase 2a trial of ASC30 to the FDA. The biotech is aiming to start the 13-week study in the U.S. at the beginning of the third quarter. Ascletis is betting big on the molecule and its broader obesity pipeline. The biotech has slashed spending on viral diseases, liver conditions and oncology to free up money for obesity and other metabolic diseases.
Pumping the money into the programs positions Ascletis to race after Novo and Lilly, jostling for position with companies including AstraZeneca, Structure Therapeutics and Viking Therapeutics. Pfizer dropped out of the race last week after one patient had a potential drug-induced liver injury. Ascletis said there were no elevations of liver enzymes during treatment with ASC30.