Roche’s oral GLP-1 receptor agonist CT-996—obtained in the $2.7 billion acquisition of Carmot Therapeutics—reduced body weight by more than 6% at four weeks versus placebo in a Phase I trial.
Roche released topline data Wednesday from an ongoing Phase I study, showing that its investigational oral GLP-1 analog CT-996 can elicit “clinically meaningful” weight-loss in patients with obesity but without type 2 diabetes.
After four weeks of treatment, patients in the CT-996 arm of the trial saw a 7.3% drop in body weight, whereas placebo counterparts saw only 1.2% weight-loss. The treatment effect of 6.1% was statistically significant in favor of Roche’s candidate, with a p-value less than 0.001, according to the company’s announcement.
The pharma did not provide any more efficacy data in its news release, but promised to present full findings and analysis of the study at an upcoming medical congress.
As for safety, CT-996 was generally well-tolerated, inducing only mild or moderate gastrointestinal side effects. None of the patients dropped out due to toxicities.
Importantly, Roche emphasized that levels of CT-996 in the blood remained consistent regardless of meal timing. CT-996 concentrations were not affected by fasting or after a high-fat meal, which suggests that the candidate can be dosed flexibly, allowing patients to take it whenever convenient.
Roche CMO Levi Garraway said in a statement that the company is “pleased” with Wednesday’s readout, saying the early data point to the potential of CT-996 to “help patients address both chronic weight management and glycemic control indications.”
Designed to be taken orally once-daily, CT-996 is an investigational small-molecule agonist of the GLP-1 receptor. By activating the GLP-1 receptor, CT-996 elicits the secretion of insulin from the pancreas in response to blood sugar levels. It also helps slow down the emptying of the stomach, which in turn suppresses appetite.
Unlike the endogenous GLP-1 hormone, however, CT-996 was specifically designed to be biased toward a specific cellular pathway, allowing it to trigger stronger glycemic control and weight-loss, while also being tolerable.
CT-996 was originally developed by Carmot Therapeutics, which Roche acquired in December 2023 for $2.7 billion upfront. After the completion of the transaction in January 2024, Roche is now fully responsible for the development of CT-996. The company is currently trialing the drug candidate for obesity and type 2 diabetes.
The Carmot buyout has been a major clinical boon for Roche, which in May 2024 reported that CT-388—another obesity asset from the acquisition—aced its Phase Ib study. After 24 weeks of follow-up, CT-388 reduced body weight by 18.8% versus placebo in healthy adults with obesity. All treated participants were able to shed at least 5% of their weight by 24 weeks, while 45% dropped 20% of their body weight at this time point.
Like CT-996, CT-388 is an agonist of the GLP-1 receptor, but also simultaneously activates the GIP receptor. The candidate also minimizes the recruitment of β-arrestin proteins in the downstream cascade of these receptors, which would otherwise weaken the treatment’s overall effect.
