Roche's Experimental Obesity Drug CT-388 Achieves 22.5% Weight Loss in Phase II Trial
核心洞察
Roche's once-weekly injectable CT-388 demonstrated statistically significant placebo-adjusted weight loss of 22.5% at 48 weeks without reaching a weight loss plateau in a Phase II trial.
The dual GLP-1/GIP receptor (搜索) agonist showed a well-tolerated safety profile with low treatment discontinuation rates and no new safety signals compared to its drug class.
Roche plans to initiate Phase III trials this quarter as the company advances into the obesity (搜索) drug market projected to reach $150 billion annually by the early 2030s.
Swiss pharmaceutical giant Roche announced positive topline results from its Phase II clinical trial of CT-388, an investigational dual GLP-1/GIP receptor (搜索) agonist for obesity (搜索) treatment. The once-weekly subcutaneous injection achieved a statistically significant placebo-adjusted weight loss of 22.5% (p < 0.001) at 48 weeks at the highest dose tested (24 mg), without reaching a weight loss plateau.
Robust Efficacy Results
The CT388-103 Phase II study enrolled 469 adults with obesity (搜索) (BMI ≥30.0 kg/m²) or overweight individuals (BMI ≥27.0 and <30.0 kg/m²) with at least one weight-related comorbidity but without type 2 diabetes (搜索). The trial demonstrated a clear dose-response relationship on weight loss, with the treatment-regimen estimand achieving 18.3% placebo-adjusted weight loss (p < 0.001).
At week 48 for the 24 mg dose, 95.7% of CT-388 treated participants achieved weight loss of ≥5%, while 87% achieved ≥10%, 47.8% achieved ≥20%, and 26.1% achieved ≥30%. Notably, 54% of participants on the 24 mg dose achieved resolution of obesity (搜索) (BMI <30 kg/m²) compared to 13% in the placebo group.
Metabolic Benefits Beyond Weight Loss
The drug demonstrated significant metabolic improvements, with 73% of participants who were pre-diabetic at baseline and treated with CT-388 at 24 mg achieving normal blood glucose levels at week 48, compared to only 7.5% in the placebo group.
Safety and Tolerability Profile
CT-388 demonstrated a safety and tolerability profile generally consistent with its drug class, with no new or unexpected safety signals. The majority of gastrointestinal-related adverse events were mild-to-moderate, consistent with the incretin class of medicines. The treatment discontinuation rate due to adverse events was low at 5.9% in CT-388 arms compared to 1.3% in the placebo arm.
Strategic Market Entry
"The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development programme as we advance to Phase III trials," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development.
Roche's decision to advance to Phase III trials marks a major step in its push to enter the fast-growing obesity (搜索) drug market that analysts estimate will be worth $150 billion annually by the early 2030s. The company expects to start Phase III trials this quarter and has designated CT-388 as a fast-track asset, significantly accelerating its clinical development.
Drug Development Background
Roche acquired CT-388 through its $2.7 billion purchase of Carmot Therapeutics (搜索) in 2023. The drug is designed as a dual GLP-1/GIP receptor (搜索) agonist that aims to reduce appetite and regulate blood sugar by selectively targeting and activating both receptors. CT-388 was engineered to have potent activation of both GLP-1 and GIP receptors with minimal β-arrestin recruitment, which minimizes receptor internalization and desensitization for prolonged pharmacological activity.
Ongoing Development Program
CT-388 is currently being investigated in an additional Phase II study (CT388-104) to evaluate efficacy, safety and tolerability in participants with obesity (搜索) or overweight who have type 2 diabetes (搜索). The phase III clinical trial programme in obesity (Enith1 and Enith2) is expected to start this quarter. Beyond standalone therapy, CT-388 is also being considered as a combination asset for petrelintide in Roche's obesity pipeline.
The full results of the CT388-103 study will be presented at an upcoming medical congress. With obesity (搜索) recognized as the greatest single risk factor for chronic disease globally, and projections showing over four billion people will be living with excess weight or obesity by 2035, Roche's advancement represents a significant development in addressing this growing healthcare challenge.