Roche announced positive topline results from two arms of an ongoing multi-part Phase I clinical trial for CT-996, an investigational, once-daily, oral small molecule GLP-1 receptor agonist for treating type 2 diabetes and obesity. The data showed that participants with obesity (but without type 2 diabetes) experienced a clinically meaningful placebo-adjusted mean weight loss of -6.1% within four weeks (p <0.001). Full study data will be presented at an upcoming medical meeting.
Obesity is a significant global health challenge, associated with comorbidities such as type 2 diabetes, cardiovascular disease, liver disease, and chronic kidney disease. More than four billion people—about 50% of the world’s population—are projected to be impacted by obesity or be overweight by 2035.
“We are pleased to see the clinically meaningful weight loss in people treated with our oral GLP-1 therapy CT-996, which could eventually help patients with chronic weight management and glycaemic control,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “This is the second positive readout from our growing metabolic pipeline in less than three months, which includes both oral and injectable options to address a spectrum of related diseases.”
CT-996 was well tolerated, with mostly mild or moderate gastrointestinal-related adverse events, consistent with the incretin drug class safety profile. There were no treatment discontinuations related to the study drug. The study results also showed that blood levels of CT-996 were largely unaffected by fasting or a standardized high-fat meal, allowing flexible dosing. CT-996 is anticipated to be used not only for glycaemic control and weight loss but also potentially for oral weight maintenance therapy following injectable-induced weight loss.
Despite numerous approved treatments, obesity and its comorbidities remain underdiagnosed and undertreated. Oral and injectable incretin therapies are critical to addressing the high unmet need, potentially preventing obesity-related complications such as type 2 diabetes and heart disease.
About CT-996 study
The CT-996-201 trial (NCT05814107) is a multi-part, multi-cohort Phase I randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of CT-996 in otherwise-healthy adults who are overweight or obese, with and without type 2 diabetes. Part 1 (completed) involved single ascending doses in 40 participants; part 2 (completed) involved multiple ascending doses in 25 participants with obesity; part 3 (planned for Q4 2024) will involve multiple ascending doses in 30 participants with obesity and type 2 diabetes. The primary endpoint is the safety and tolerability of CT-996; secondary endpoints include the assessment of pharmacokinetics and effects on body weight and glucose homeostasis. Based on current Phase I results, CT-996 will advance to Phase II clinical development.
About CT-996
CT-996 is an investigational, once-daily, oral small molecule GLP-1 receptor agonist for the treatment of type 2 diabetes and obesity. Unlike the endogenous GLP-1 hormone, CT-996 is designed as a biased GLP-1 receptor agonist that activates cAMP signaling with minimal-to-no beta-arrestin recruitment, expected to result in strong glycaemic control, significant weight loss, and good tolerability.
About Roche’s metabolism portfolio
Roche’s R&D portfolio includes incretin-based assets to address obesity, diabetes, and other cardiometabolic indications. The portfolio ranges from orals to injectables, including:
- CT-388, an investigational dual GLP-1/GIP receptor agonist for treating obesity in patients with and without type 2 diabetes, in Phase II. Injected subcutaneously once a week, it has potential as a standalone or combination therapy for chronic weight management and type 2 diabetes.
- CT-996, an investigational, once-daily, oral small molecule GLP-1 receptor agonist in Phase I, with potential as a best-in-class oral treatment for type 2 diabetes and chronic weight management.
- CT-868, an investigational, once-daily, subcutaneous dual GLP-1/GIP receptor agonist in Phase II, with potential as a first-in-class treatment for glycaemic control as an adjunct to insulin in patients with type 1 diabetes.
Incretins are gut hormones that modulate blood glucose by stimulating insulin secretion and suppressing appetite. Emerging data suggest broader effects in the liver, heart, and brain, indicating potential beyond glucose modulation. Incretins are becoming the standard of care in obesity treatment and may be effective in other metabolic, cardiovascular, and chronic kidney diseases.
