A Roche obesity drug designed to hit two targets led to weight loss that is competitive with other drugs in its class, but from a development standpoint, the drug candidate still trails rival medicines that are already commercialized or in late-stage testing. That means differentiation from the crowded metabolic medicines field may need to come from tests of the weekly injection as part of a combination treatment.
According to the preliminary Phase 2 data released Tuesday, the Roche drug, CT-388, led to a placebo-adjusted 22.5% weight loss for the highest dose tested measured at 48 weeks. At that time point, the weight loss did not plateau, suggesting that more weight could be lost with longer treatment. Roche said 54% of study participants who received this 24 mg dose achieved resolution of obesity compared to 13% in the placebo group.
Without reporting specific details, Roche said gastrointestinal side effects were classified as mild to moderate and consistent with other drugs in this class of medicines. The discontinuation rate due to adverse effects was 5.9% in the study drug arm compared to 1.3% in the placebo arm.
Roche said full study results will be presented at an upcoming medical meeting. A separate Phase 2 study is evaluating CT-388 in patients with obesity or overweight who also have type 2 diabetes. Roche plans to advance CT-388 to Phase 3 testing in obesity in the current quarter.
CT-388 is a peptide designed to activate the GLP-1 and GIP receptors. Those are the same targets hit by Eli Lilly’s blockbuster obesity drug, Zepbound. But Roche’s drug, the most advanced program from the $2.7 billion acquisition of Carmot Therapeutics in 2023, came from a platform technology that develops drugs that offer “biased signaling,” which is the emphasis of pathways desirable for a drug. In the case of CT-388, the biased signaling for this once-weekly injectable drug is expected to prolong its pharmacological activity.
Roche added to its metabolic medicines pipeline again last year, paying $1.65 billion to begin a partnership on Zealand Pharma’s petrelintide. This once-weekly injectable peptide drug is designed to activate the amylin receptor to promote satiety. Targeting amylin is also hoped to offer better tolerability and muscle preservation. When the deal was announced, Roche said it was interested in testing petrelintide in combination with CT-388. Other companies developing drugs that target the amylin receptor include AbbVie and Novo Nordisk.
William Blair analyst Andy Hsieh said in a research note that the limited data released by Roche make it difficult to draw solid conclusions about how CT-388 compares to Lilly’s Zepbound or dual GLP-1/GIP agonists in late-stage development by Kailera Therapeutics and Viking Therapeutics. He said the firm is encouraged by the low discontinuation rates for the entire study, but is most interested in the rate for the high-dose 24 mg arm. Further differentiation could come from tests of the drug in combination with petrelintide.
“In our view, this combination could offer increased potency, with potential to address individuals with higher BMI aiming to achieve normal weight,” Hsieh said. “We believe this approach could differentiate the regimen as it enters an increasingly crowded and competitive obesity landscape.”
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