Structure announces mid-phase data for its oral GLP-1 candidate

Structure Therapeutics' daily, oral GLP-1 drug candidate led to substantial weight loss in two mid-stage studies but also resulted in gastrointestinal issues, the company said yesterday.

In the core phase 2b Access trial, the company's investigational GLP-1 pill, aleniglipron, was tested in 230 adults with obesity or overweight and at least one weight-related health condition. Participants either started on a 5 mg dose and increased over four weeks to 45, 90 or 120 mg daily or received a placebo.

After 36 weeks, patients taking the highest dose (120 mg) lost a placebo-adjusted average of 11.3% of their weight. Overall, 86% of participants lost at least 5% of body weight, while 70% lost at least 10%.

Aleniglipron also delivered clinically meaningful reductions in systolic blood pressure and lowered HbA1c.

As is typical for the GLP-1 drug class, the most frequent adverse events were gastrointestinal -- nausea and vomiting being the two most common side effects during the titration phase.

Adverse event–related discontinuations ranged from 7.7% to 13.3% across doses, averaging 10.4% across all active treatment groups, the company said.

The second study is a separate, ongoing 44-week exploratory trial that tests two higher doses of aleniglipron (180 and 240 mg) in 85 adults with obesity or overweight who also have at least one weight-related comorbidity.

Participants in the higher-dose trial were either given a placebo or 5 mg of aleniglipron, which was titrated over four weeks to one of three target doses, including the highest dose from the first phase 2b study.

The placebo-adjusted weight loss was 14.1%, 14.4% and 15.3% for the 120, 180 and 240 mg doses, respectively, according to the released data.

Both studies in the Access program showed dose-dependent weight reductions without evidence of a plateau, the company said.

Aleniglipron also appears to be tolerated about the same as other GLP-1 therapies, even at daily doses up to 240 mg, with the most common adverse events being gastrointestinal.

"The topline results show that aleniglipron is differentiated and delivered clinically meaningful, competitive and dose-dependent weight loss with a safety profile appropriate for chronic use in a disease that impacts millions of people," Raymond Stevens, Ph.D., Structure Therapeutics' CEO, said in a company press release. "For the higher doses, the observed weight loss data at 36 weeks with no weight loss plateau is potentially best-in-class for oral small-molecule GLP1s."

Structure's announcement comes the same day that Chinese biotech Ascletis Pharma reported mid-stage U.S. trial data for its oral GLP-1 candidate, ASC30, which may offer a competitive edge in terms of gastrointestinal tolerability.

That said, Structure Therapeutics is also running a 40-week phase 2 study with 71 adults to test aleniglipron's effect on body fat. Participants in the trial start at 2.5 mg and increase every four weeks to 120 mg.

Data from an interim analysis with a median follow-up of roughly 10 weeks showed that initiating treatment at a lower dose of 2.5 mg for the first four weeks significantly improved tolerability compared with starting at 5 mg, with no adverse-event–related discontinuations observed at either the initial 2.5 mg or the subsequent 5 mg dose.

These encouraging early weight-loss results provide a foundation for advancing aleniglipron to phase 3 testing, the company stated.

Structure Therapeutics is planning for an end-of-phase 2 meeting with the FDA early next year and could begin late-stage trials for aleniglipron by mid-2026.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.