Roche announced topline results from its CT388-103 Phase II obesity trial, showing once-weekly injections of CT-388 titrated up to 24 mg produced a placebo-adjusted mean weight loss of 22.5% (p < 0.001) at 48 weeks. In the highest-dose cohort (n ≈ 90), 95.7% of participants achieved ≥5% weight loss, 87.0% achieved ≥10%, 47.8% achieved ≥20% and 26.1% achieved ≥30%, with no evidence of a weight-loss plateau over the study period. The trial enrolled 469 adults with BMI ≥30 kg/m2 or BMI ≥27 kg/m2 plus one weight-related comorbidity, excluding type 2 diabetes.

Beyond weight reduction, CT-388 delivered marked metabolic benefits. Among participants classified as pre-diabetic at baseline and treated with 24 mg of CT-388, 73% achieved normoglycemia (fasting glucose <100 mg/dL) by week 48 versus 7.5% in the placebo arm. The trial also recorded statistically significant improvements in waist circumference, systolic blood pressure (mean reduction of 12 mm Hg) and lipid profiles (mean LDL-C reduction of 18 mg/dL), underscoring the compound’s potential to address multiple cardiometabolic risk factors.

CT-388 was generally well-tolerated, with gastrointestinal adverse events (nausea, diarrhea) predominantly mild to moderate in intensity and occurring during dose titration. Discontinuation rates due to treatment-emergent adverse events were 5.9% in CT-388 arms compared with 1.3% in placebo. No new or unexpected safety signals emerged, and serious adverse events were balanced across active and control groups. These attributes mirror those seen with established incretin-based therapies and de-risk the asset ahead of larger trials.

With fast-track designation secured, Roche plans to initiate two pivotal Phase III studies (Enith1 and Enith2) this quarter, targeting primary completion by 2028. CT-388 will be evaluated both as monotherapy and in combination with petrelintide, positioning Roche in the competitive GLP-1/GIP space dominated by peers. Given the projected global obesity prevalence exceeding four billion individuals by 2035, successful late-stage data could underpin a multi-billion-dollar franchise, potentially contributing 2–4% annual revenue growth and reinforcing Roche’s role as a value play in cardiometabolic innovation.