Genentech Reports Positive Phase I Results for Oral GLP-1 Agonist CT-996 in Obesity Treatment

In a significant development, Genentech, a Roche Group member, has revealed promising results from two segments of its ongoing Phase I clinical trial for CT-996, an oral small molecule GLP-1 receptor agonist under investigation for treating type 2 diabetes and obesity. The clinical trial results indicated a meaningful placebo-adjusted mean weight loss of -6.1% within four weeks for participants with obesity but not type 2 diabetes.

The detailed study data is scheduled for presentation at an upcoming medical meeting. Obesity remains one of the world’s most pressing health issues, associated with numerous comorbidities like type 2 diabetes, cardiovascular disease, liver disease, and chronic kidney disease. It is estimated that by 2035, over four billion people, which is about half of the global population, will be impacted by obesity or be overweight.

Dr. Levi Garraway, Genentech’s chief medical officer and head of Global Product Development, expressed satisfaction with the weight loss results observed in the trial. He highlighted that CT-996 could potentially aid in managing chronic weight and glycemic control. This is the second positive outcome from Genentech's metabolic pipeline within a short period, following data on CT-388, another therapeutic option under development. This pipeline includes both oral and injectable treatments addressing a spectrum of related diseases.

CT-996 was generally well-tolerated, with participants experiencing mild to moderate gastrointestinal-related side effects, consistent with other incretin drugs. Importantly, no participants discontinued the study due to adverse effects. The study also found that CT-996 blood levels remained stable regardless of fasting or consuming a high-fat meal, suggesting that the medication could be taken without strict meal timing, offering greater flexibility for patients.

Based on these findings, CT-996 shows promise not just for glycemic control and weight loss but potentially as an oral weight maintenance therapy following initial weight loss from injectable treatments. Despite a variety of treatments available, obesity and its related conditions remain largely underdiagnosed and undertreated, continuing to exert a growing impact on society.

Oral and injectable incretin therapies are essential to meet the high unmet needs in this area. They could potentially provide broader access and aid in preventing comorbidities or complications associated with obesity, such as type 2 diabetes and cardiovascular diseases.

The CT-996 study, officially designated as CT-996-201, is a multi-part, multi-cohort Phase I trial that is randomized, double-blind, and placebo-controlled. It aims to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of CT-996 in overweight or obese adults, both with and without type 2 diabetes. The trial's first part involved a single ascending dose study with 40 participants, while the second part included multiple ascending doses in 25 participants with obesity but not type 2 diabetes. The third part, planned for Q4 2024, will involve multiple ascending doses in 30 participants with both obesity and type 2 diabetes. The primary focus of the trial is on safety and tolerability, while secondary goals include evaluating the pharmacokinetics and impact on body weight and glucose regulation. Based on the current Phase I outcomes, CT-996 is set to progress to Phase II clinical development.

CT-996, a once-daily oral GLP-1 receptor agonist, is specifically designed to activate cAMP signaling with minimal beta-arrestin recruitment, differentiating it from endogenous GLP-1 hormones. These properties are anticipated to result in robust glycemic control, significant weight loss, and good tolerability.

Genentech's metabolism portfolio aims to address the diverse needs of patients with obesity through a range of incretin-based therapeutic options, spanning both oral and injectable forms, and including novel mechanisms of action. This comprehensive approach is intended to provide effective treatments for obesity, diabetes, and other cardiometabolic conditions. Incretins, gut hormones that help regulate blood glucose and suppress appetite, have shown potential benefits beyond glucose control, impacting multiple organs including the liver, heart, and brain. This broader biological effect underscores their role as a new standard of care in treating obesity and related metabolic disorders.