Ascletis Pivots Strategy in Oral GLP-1 Race, Opts for Low and Slow Approach

Ascletis, a key player in the competitive oral GLP-1 market, has announced a strategic shift in its clinical approach for its obesity treatment candidate, ASC30. The company's decision to adopt a "low and slow" dose titration regimen comes as the pharmaceutical industry intensifies its focus on developing oral alternatives to injectable weight loss medications.

Phase 1b Trial Results Inform New Direction

Recent data from Ascletis' phase 1b trial of ASC30 has led the company to reevaluate its dosing strategy. The trial, which included three cohorts, tested various dosing regimens to determine the most effective and tolerable approach for patients.

The third cohort, which employed a high starting dose of 5 mg rapidly titrated up to 60 mg, showed no significant benefit over lower, more gradual dosing schemes. After 28 days, patients in this cohort experienced a mean weight loss of 4.8%, with two outliers reporting only 1.8% weight reduction.

In contrast, earlier cohorts that began with a 2 mg dose and increased to either 20 mg or 40 mg demonstrated comparable efficacy with better tolerability. The second cohort, in particular, achieved a placebo-adjusted weight loss of 6.5%, slightly outperforming the 6.1% seen in the third cohort after adjusting for outliers.

Gastrointestinal Tolerability Drives Decision

Ascletis' decision to pursue a lower, slower titration regimen was primarily influenced by gastrointestinal tolerability data. While no grade 3 or higher adverse events were reported across all cohorts, the high-dose, fast-titration model showed the worst safety and tolerability profile.

The company reported that most gastrointestinal-related adverse events in the first two cohorts were grade 1 and short-lived. Ascletis claims that the gastrointestinal tolerability in these arms was similar to or better than competing oral GLP-1 candidates, specifically mentioning Eli Lilly's orforglipron.

Implications for the Oral GLP-1 Market

Ascletis' strategic pivot comes at a critical time in the oral GLP-1 market. With Novo Nordisk recently filing for FDA approval and Eli Lilly planning to submit phase 3 data in obesity later this year, competition is intensifying. The potential for oral formulations to provide an easier administration route compared to injected medications like Wegovy and Zepbound has positioned this segment as a promising next-generation approach in the rapidly growing anti-obesity market.

To capitalize on this opportunity, Ascletis has submitted a protocol for a phase 2a trial of ASC30 to the FDA, aiming to commence the 13-week study in the U.S. at the beginning of the third quarter. This move aligns with the company's broader strategy to prioritize obesity and metabolic diseases, having recently reduced spending on viral diseases, liver conditions, and oncology programs.

As the race for oral GLP-1 treatments heats up, Ascletis joins a competitive field that includes industry giants like AstraZeneca, as well as emerging players such as Structure Therapeutics and Viking Therapeutics. The recent exit of Pfizer from this race due to safety concerns further underscores the challenges and opportunities in this high-stakes market.