• A once-weekly subcutaneous injection of CT-388 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 
• 54% of participants on the 24 mg dose achieved resolution of obesity (BMI <30 kg/m2) vs. 13% in the placebo group
• CT-388 demonstrated a safety and tolerability profile generally consistent with its drug class with no new or unexpected safety signals

- Roche (SIX: RO, ROG; OTCQX: RHHBY) announced positive topline results from CT388-103, a Phase II clinical trial of CT-388, an investigational dual GLP-1/GIP receptor agonist being developed for the treatment of obesity. The study found that once-weekly subcutaneous injections of CT-388 (titrated up to 24 mg) resulted in significant and clinically meaningful placebo-adjusted weight loss of 22.5% (efficacy estimand) without reaching a weight loss plateau at 48 weeks. A clear dose-response relationship on the weight loss was observed. For the treatment-regimen estimand, the placebo-adjusted weight loss achieved with CT-388 was 18.3% (p-value < 0.001). At week 48 for the 24 mg dose, 95.7% of CT-388 treated participants achieved a weight loss of ≥5%, 87% achieved ≥10%, 47.8% achieved ≥20%, and 26.1% achieved ≥30%. 73% of participants who were pre-diabetic at baseline and treated with CT-388 at 24 mg achieved normal blood glucose levels at week 48 compared to 7.5% in the placebo group. 

The treatment was well-tolerated, with the majority of gastrointestinal-related adverse events being mild-to-moderate, generally consistent with the incretin class of medicines. In addition, the treatment discontinuation rate due to adverse events was low (5.9% in CT-388 arms; 1.3% in placebo arm). The full results of the study will be presented at an upcoming medical congress.

“We are pleased to see such meaningful weight loss in people treated with CT-388,” said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. “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.” 

With its growing cardiometabolic portfolio and strong diagnostic expertise, Roche is advancing transformative standards of care to improve the lives of people living with cardiometabolic diseases as well as reducing the significant burden on healthcare systems and society.

Obesity is recognised as the greatest single risk factor for chronic disease globally. By 2035, over four billion people (more than half of the global population) are projected to be living with excess weight or obesity, a trend affecting nearly every country. This rise is driven by a complex mix of genetics and biology as well as behavioural, environmental and socioeconomic factors, placing an increased strain on healthcare systems due to the associated burden of comorbidities and reduced quality of life.

Since integrating CT-388 into the Roche pipeline, we have designated it as a fast-track asset and significantly accelerated its clinical development to bring this potential therapy to patients. CT-388 is currently being investigated in an additional Phase II study (CT388-104) to evaluate the efficacy, safety and tolerability of CT-388 in participants who are living with obesity or are overweight and have T2D. The phase III clinical trial programme of CT-388 in obesity (Enith1 and Enith2) is expected to start this quarter. In addition to offering robust efficacy as a standalone therapy, CT-388  also plays a key role in unlocking the promise of our obesity pipeline and is considered as a combination asset for petrelintide.