Structure surges on early glimpse of oral GLP-1 drug for weight loss
29 Sep 2023
Clinical ResultPhase 2Phase 1
Shares in Structure Therapeutics jumped more than 90% in premarket trading on Friday after the company reported results from an early-stage trial showing that its oral GLP-1 receptor agonist, GSBR-1290, led to placebo-adjusted weight loss of about 5% following four weeks of treatment. "These positive Phase Ib results support GSBR-1290 as a promising, differentiated oral GLP-1 receptor agonist with once-daily dosing," remarked CEO Raymond Stevens.
The multiple ascending-dose study focused on the safety and tolerability of GSBR-1290 in 24 overweight or obese individuals who were otherwise healthy. Participants were randomised to GSBR-1290 or placebo across three dose cohorts with target doses of 30mg, 60mg or 90mg. According to top-line results after four weeks of once-daily dosing, subjects in the highest- and middle-dose groups saw 4.9% and 4.6% decreases in weight compared to placebo. For the lowest-dose cohort, the difference was only 1.1% versus placebo.
Structure said GSBR-1290 also demonstrated an encouraging safety and tolerability profile, with no adverse event (AE)-related discontinuations. Side effects were typically mild and expected for the GLP-1 class, according to the company. The two most common issues were nausea and vomiting, with higher incidences observed in the 60mg and 90mg cohorts compared to placebo, while the drugmaker noted that "there were no clinically meaningful changes in liver function tests."
Leerink Partners Research analyst David Risinger said Structure "delivered better-than-expected efficacy and tolerability" for its oral drug. Meanwhile, analysts at BMO Capital Markets called the lack of AE-related discontinuations “promising and likely ahead of investor expectations.”
Data snag delays Phase II reveal
"We look forward to sharing results of GSBR-1290 over a longer 12-week period in the Phase IIa study, and we continue to move forward with all activities in order to begin Phase IIb clinical trials in both type 2 diabetes and obesity as planned in 2024," Stevens said. Structure was initially intending to unveil Phase IIa results from the obesity trial by the end of this year, but a data collection omission at a clinical site resulted in weight not being collected at the final week 12 visit for 24 of the 40 participants.
Structure said it will enrol additional participants in the Phase IIa obesity cohort to replace those whose 12-week weight data was not collected. As a result, while top-line results from the diabetes cohort continue to be expected in the latter half of the fourth quarter, data from the obesity cohort are now due in the first half of 2024.
Rivals further ahead
Eli Lilly reported mid-stage study data in June showing that its experimental oral GLP-1 receptor agonist orforglipron was associated with dose-dependent body weight reductions ranging from 8.6% to 12.6% after 26 weeks, versus 2% for placebo. Body weight continued to decrease at 36 weeks, with orforglipron achieving reductions ranging from 9.4% to 14.7%, compared to 2.3% in the placebo group.
Pfizer and Novo Nordisk have also shared results for their respective oral GLP-1s under development. In May, Pfizer said a Phase IIb study of danuglipron showed significantly reduced body weight versus placebo in adults with type 2 diabetes. At around the same time, Novo Nordisk said obese and overweight patients who took its oral version of Wegovy (semaglutide) achieved weight loss of 17.4% after 68 weeks compared with only 1.8% for placebo.
However, the competitive landscape has prompted some to pull back. In June, AstraZeneca decided to terminate a Phase I trial of its oral GLP-1 candidate AZD0186, hinting that it would not have been able to set itself apart from other assets further along in development or already on the market.
However, BMO Capital Markets analysts suggested the data for Structure's GSBR-1290 is "highly competitive versus orfoglipron on efficacy and tolerability. While too early to conclude superiority, [GSBR-1290] compares favourably to early orforglipron data in similar patients." Eli Lilly's candidate was tied to 3.6kg placebo-adjusted weight loss at week four. BMO analysts said GSBR-1290 is also "staunchly ahead" of danuglipron, which is dosed twice daily (for more, see Spotlight On: Obesity trials to watch).
$300M private placement
Separately on Friday, Structure also announced a $300-million private placement financing, with "participation from a number of large healthcare dedicated institutional and mutual fund investors." Proceeds will go toward accelerating GSBR-1290’s development as well as other programmes from the company's oral incretin franchise, Stevens said. The company went public in February, raising around $185 million from the sale of its stock.
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