Structure Therapeutics has shared an early look at the efficacy of its oral GLP-1 receptor agonist, linking the candidate to a 5% reduction in weight after four weeks. But a mistake in a larger, longer clinical trial has pushed back data that will give a clearer picture of how its candidate holds up against rival oral obesity drugs in development at Eli Lilly, Novo Nordisk and Pfizer.
San Francisco-based Structure rode rising interest in targeting GLP-1 to treat obesity to pull off a $185 million IPO earlier this year. The biotech’s lead candidate is an oral small molecule that it argues is easier to use than obesity and diabetes injectables such as Lilly’s Mounjaro and Novo’s Ozempic and has a wider safety window than oral candidates in development at a clutch of leading drugmakers.
Structure has begun to deliver clinical data on its candidate, GSBR-1290, reporting single ascending dose results in June and following up with another readout Friday. The latest look at the drug candidate comes from a phase 1b multiple ascending dose trial.
In the study, 24 healthy overweight or obese individuals received one of three doses of GSBR-1290 or placebo. After four weeks of once-daily dosing, participants on the highest dose had a 4.9% reduction in weight compared to their counterparts on placebo. The reduction at the middle dose, 4.6%, was similar, but the difference versus placebo fell away to 1.1% at the lowest dose.
Structure’s study is small, and cross-trial comparisons are unreliable, but the result suggests GSBR-1290 is competitive. The candidate is more convenient than Pfizer’s danuglipron and Novo Nordisk’s oral semaglutide—which are given twice daily and on an empty stomach with a sip of water, respectively—and posted similar weight loss figures to Lilly’s orforglipron at four weeks.
On the safety front, the most common adverse events were classwide issues, nausea and vomiting, which affected more patients in the higher two dose arms than in the placebo group. Structure said it saw no “clinically meaningful changes in liver function tests.” Pfizer dropped one of its oral obesity candidates earlier this year in response to a liver safety signal, although it is continuing to advance another asset.
One problem for Structure is that its rivals are deeper in development. Novo already has phase 3 data on its contender, and Lilly and Pfizer have finished phase 2 studies of their assets. The presence of advanced rivals led AstraZeneca to cull its early-phase candidate, citing a lack of differentiation, but Structure sees a space for GSBR-1290.
The biotech, which was co-founded by, and works with, Schrödinger, had planned to share obesity data from a phase 2a trial that could support its differentiation argument by the end of the year. However, a clinical site failed to collect weight data for 24 of the 40 participants at the final, Week 12 visit, forcing Structure to enroll additional participants. As such, while the diabetes cohort will report out as planned, Structure delayed obesity data to the first half of next year. Structure also aims to enter phase 2b in 2024.
As Structure gathers longer-term data on GSBR-1290, it should, based on the experience of its rivals, see patients lose more and more weight. Lilly reported a 12.4%, placebo-adjusted reduction in weight after 36 weeks, which could increase at later time points, but it expects the figure to fall short of the efficacy of injectables.
The forecast efficacy gap has raised doubts about whether people will prefer injectables, but Lilly sees an opportunity for orals, particularly in “middle-income markets in China” where price is a bigger factor.