Possibly adding a new entrant to the highly competitive diabetes/weight loss market, Roche has announced positive interim results from an ongoing Phase I trial for its oral small molecule GLP-1 receptor agonist, CT996. The drug is being developed for both type 2 diabetes and obesity, and the company says treatment in patients with both conditions resulted in a clinically meaningful weight loss.
Treatment with CT-996 in participants with obesity, but without type 2 diabetes, led to a mean weight loss of -6.1% within four weeks.The company says full study data will be presented at an upcoming medical meeting.
The global weight loss drug market alone was estimated to be worth almost $4B in 2023, and is expected to grow to over $44B by 2029. Emergence of highly effective GLP-1 agonists, such as Novo’s semaglutide (Ozempic, Wegovy, and Rybelsus) and liraglutide (Saxenda), and Lilly’s tirzepatide (Mounjaro) has completely transformed the market for weight loss and diabetes 2. Many companies are now developing GLP-1 agonists they believe can carve a niche or even dominate in this market.
“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, Roche’s CMO and head of global product development.
Obesity causes several serious comorbidities, including type 2 diabetes, cardiovascular disease, liver disease, and chronic kidney disease. More than four billion people—about 50 percent of the world’s population—are estimated to be impacted by obesity or will be overweight by 2035.
CT-996 is a once-daily, oral small molecule GLP-1 receptor agonist. The drug is specifically designed to be a biased GLP-1 receptor agonist that activates cAMP signaling with minimal-to-no beta-arrestin recruitment. These signaling properties are expected to lead to strong glycemic control, significant weight loss and good tolerability.
In this latest trial, CT-996 was well tolerated, with mostly mild or moderate gastrointestinal-related adverse events, consistent with the safety profile of the incretin drug class. There were no treatment discontinuations related to the study drug.
The study also showed that blood levels of CT-996 were largely unaffected either during fasting or after a standardized high-fat meal, suggesting the drug could potentially be dosed without regard to meal timing. The drug is expected to be not only used to achieve glycemic control and inducing weight loss, but also potentially for oral weight maintenance therapy following weight loss induced by injectables.
Oral and injectable incretin modalities, such as GLP-1 agonists “are critical to address the high unmet need in the obesity market,” Roche said in its press release. Incretin is a broader term for gut hormones that aid in digestion and blood glucose (sugar) control, including glucagon-like peptide-1 (GLP-1).
Roche is moving aggressively into this space, stating that its, “R&D portfolio of incretin-based clinical and preclinical assets has great potential to address patients’ needs by providing treatments as mono and combination therapy for obesity, diabetes and various other cardiometabolic indications.”
