Medical Innovation Exchange

Structure tumbles as midphase oral GLP-1 data underwhelm investors

Eli Lilly is casting a long shadow over the GLP-1 market. Structure Therapeutics linked its oral candidate to significant reductions in blood sugar and weight in a phase 2a trial on Monday, only for investors to halve the biotech’s share price as they assessed the results in light of the competitive landscape.

Structure is one of a clutch of companies working on oral alternatives to injectable GLP-1 drugs such as Lilly’s Mounjaro and Novo Nordisk’s Ozempic. The biotech shared four-week, phase 1b data on the drug candidate, GSBR-1290, in September and followed up with an early look at the results of a phase 2a trial this week.

The phase 2a study features a cohort of people with type 2 diabetes, who received one of two doses of GSBR-1290 or placebo, and another cohort of people with obesity who received a higher dose of the study drug or placebo. Structure tracked weight change in both cohorts. 

After eight weeks of daily dosing, the biotech tracked a 4.74%, placebo-adjusted reduction in weight in the obesity group. The 12-week figures for the diabetes cohort were 3.51% at the lower dose and 3.26% at the higher dose. Structure also tracked a 1% placebo-adjusted reduction in HbA1C, a measure of blood sugar, in the diabetes trial at week 12.

Comparing those figures with the results of other trials is fraught with difficulties but, with that caveat, the obesity weight loss looks slightly smaller than at the same time point in Lilly’s phase 2 study in the indication. A clearer picture will only emerge as Structure collects longer-term data in more patients. 

Structure has seen enough to commit to generating that data. Week 12 data in obesity are scheduled for the second quarter and the biotech plans to move into phase 2b by the end of next year. The plans are built on the signs of efficacy and an encouraging tolerability profile. 

Almost all participants had a treatment-emergent adverse event but most were of moderate severity. One subject dropped out because of an adverse event and one participant, who was diagnosed with fatty liver disease while in the study, had elevated liver enzymes without an increase in bilirubin. Effects on the liver and high dropout rates have affected trials of some other oral GLP-1 drugs, including one developed by Pfizer that was ultimately dropped

In a statement, Structure CEO Raymond Stevens, Ph.D., pitched the results as evidence that GSBR-1290 “has the potential to be a best-in-class compound and a backbone for future combinations,” while noting the scope to “further optimize” performance.

Investors remain unconvinced, though, and sent shares in Structure down 50% to just under $29 as the markets opened Monday.

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