Roche reports positive Phase I results for oral GLP-1 agonist CT-996 in obesity treatment

Roche has announced promising top-line results from two segments of its ongoing multi-part Phase I clinical trial for CT-996, a novel, once-daily, oral GLP-1 receptor agonist. CT-996 is aimed at treating type 2 diabetes and obesity. The results showcased a significant placebo-adjusted mean weight loss of -6.1% in participants with obesity and without type 2 diabetes over a four-week period. The data will be formally presented at an upcoming medical conference.

Obesity is a critical global health challenge, correlated with multiple comorbidities including type 2 diabetes, cardiovascular disease, liver disease, and chronic kidney disease. It is estimated that by 2035, over four billion people, or approximately 50% of the world’s population, will be affected by obesity or will be overweight.

Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development, expressed optimism over the results. He highlighted that the weight loss observed in patients treated with CT-996 could pave the way for addressing both chronic weight management and glycaemic control. This trial follows closely on the heels of positive data from another compound in the company’s metabolic pipeline, CT-388.

CT-996 was well-tolerated, with most adverse events being mild or moderate and gastrointestinal in nature, consistent with the known safety profile of the incretin drug class. Importantly, no participants discontinued treatment due to adverse effects. The pharmacokinetic data suggested that CT-996 could be dosed independently of meal timings, offering greater flexibility to patients. This trial also indicated that CT-996 could potentially serve as a weight maintenance therapy following initial weight loss achieved through injectable treatments.

Despite numerous approved therapies, the overall trajectory for obesity and its related conditions remains largely unchanged. These health issues are typically underdiagnosed and undertreated, exacerbating their societal impact. The need for both oral and injectable incretin-based therapies remains high. These treatments could not only broaden patient access but also help prevent complications related to obesity, such as type 2 diabetes and cardiovascular diseases.

The CT-996-201 trial (NCT05814107) is a comprehensive Phase I study designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of CT-996. Conducted in otherwise healthy adults who are overweight or obese, with and without type 2 diabetes, the trial consists of multiple parts. Part 1 involved single ascending doses in 40 participants, now completed. Part 2, also completed, included multiple ascending doses in 25 participants with obesity but without type 2 diabetes. Part 3 will involve multiple ascending doses in 30 participants with both obesity and type 2 diabetes, and is set to commence in Q4 2024. The primary endpoint focuses on the safety and tolerability of CT-996, with secondary endpoints examining its pharmacokinetics and effects on body weight and glucose homeostasis. Based on these Phase I results, further Phase II clinical development for CT-996 is planned.

CT-996 is notably distinguished from endogenous GLP-1 as it specifically acts as a biased GLP-1 receptor agonist, activating cAMP signaling with minimal beta-arrestin recruitment. These targeted properties are expected to result in significant glycaemic control, notable weight loss, and good tolerability.

Obesity is a complex disease, and Roche’s research and development portfolio of incretin-based assets shows potential to meet varied patient needs. This portfolio includes CT-388, an investigational dual GLP-1/GIP receptor agonist currently in Phase II trials, and CT-868, another dual GLP-1/GIP receptor agonist in Phase II development, aimed at enhancing glycaemic control in patients with type 1 diabetes. Collectively, these therapeutic options underscore Roche’s commitment to addressing the multifaceted needs of patients with obesity and related metabolic conditions.