CT-996 Demonstrates Significant Weight Loss in Patients with Obesity and Type 2 Diabetes

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Results from a Phase I clinical trial for CT-996, an oral GLP-1 receptor agonist designed to treat obesity and type 2 diabetes, showed a placebo-adjusted mean weight loss of 6.1% within four weeks. According to the company, full data will be presented at an upcoming medical meeting. Different from the endogenous GLP-1 hormone, CT-996 is specifically designed to be a biased GLP-1 receptor agonist that activates cAMP signaling with minimal-to-no beta-arrestin recruitment.¹

"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 address both chronic weight management and glycemic control indications,” said Levi Garraway, MD, PhD, chief medical officer, head, global product development, Roche, in a press release. “Following our data for CT-388, this is the second positive readout in less than three months from our growing metabolic pipeline, which includes both oral and injectable options to address patients' needs across a spectrum of related diseases."

The multi-part, multi-cohort, double-blind, placebo-controlled, single- and multiple- ascending dose CT-996-201 trial was designed 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 consisted of 40 participants who were overweight or obese with a single ascending dose, while Part 2 involved a multiple ascending dose in three sequential cohorts of 25 participants with obesity without type 2 diabetes. Part 3 is a multiple ascending dose study in two sequential cohorts of 30 participants with obesity and type 2 diabetes, with plans to begin later this year. The trial’s primary endpoint is safety and tolerability of CT-996, with secondary endpoints including the assessment of the pharmacokinetics of CT-996 and its effects on body weight and glucose homeostasis.

CT-996 was found to be well tolerated, with most adverse events (AEs) being mild or moderately gastrointestinal-related. Additionally, there were no treatment discontinuations that resulted from treatment with the drug. Results also indicated that the treatment did little to change blood levels either during fasting or after a standardized high-fat meal, suggesting that it could be dosed without regard to meal timing.¹

According to a study published in the Journal of the American Heart Association, obesity contributes anywhere from 30% to 53% of all new diabetes cases in the United States on an annual basis. More than 31 million Americans struggle with type 2 diabetes, according to the Centers for Disease Control and Prevention (CDC). Further, the number of deaths from type 2 diabetes in people under the age of 65 years is increasing, as are complications that result from the condition, such as amputations and hospitalizations.²

“Our study highlights the meaningful impact that reducing obesity could have on Type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority. Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity and developing community programs to prevent obesity, could substantially reduce new cases of Type 2 diabetes,” explained Natalie A. Cameron, MD, resident physician of internal medicine, McGaw Medical Center of Northwestern University, Chicago, study author, in a press release.

Roche anticipates that CT-996 will not only aid in glycemic control and weight loss but also serve as a potential maintenance therapy post-weight loss induced by injectables.¹

References

1. [Ad hoc announcement pursuant to Art. 53 LR] Roche announces positive Phase I results of its oral GLP-1 receptor agonist CT-996 for the treatment of people with obesity. Roche. July 17, 2024. Accessed July 17, 2024. https://www.roche.com/media/releases/med-cor-2024-07-17

2. Obesity contributes to up to half of new diabetes cases annually in the United States. American Heart Association. February 10, 2021. Accessed July 17, 2024. https://newsroom.heart.org/news/obesity-contributes-to-up-to-half-of-new-diabetes-cases-annually-in-the-united-states