Genentech Announces Positive Phase Ib Results for Dual GLP-1/GIP Agonist CT-388 in Obesity

Genentech, a prominent member of the Roche Group, has recently reported promising results from the Phase Ib clinical trial of CT-388, a novel dual GLP-1/GIP receptor agonist aimed at treating obesity and type 2 diabetes. The study demonstrated that administering CT-388 once a week through subcutaneous injections over a 24-week period led to substantial weight loss in participants with obesity, significantly outperforming the placebo.

The trial's findings revealed that CT-388 induced an average placebo-adjusted weight loss of 18.8%, which is both clinically meaningful and statistically significant. By the 24th week, all participants receiving CT-388 experienced more than 5% weight loss, with 70% achieving over 15% loss and 45% reaching 20% or more. Importantly, for participants with pre-diabetes at the start of the trial, CT-388 successfully normalized their blood sugar levels, underscoring its potential in managing glucose homeostasis.

Safety data from the trial indicated that CT-388 was generally well-tolerated. The most common adverse events were mild to moderate gastrointestinal issues, a known side effect of incretin-based treatments. No unexpected safety concerns emerged, reinforcing the safety profile of CT-388 within its drug class.

Levi Garraway, M.D., Ph.D., Genentech’s chief medical officer and head of Global Product Development, expressed optimism about the results. He highlighted the significant and clinically meaningful weight loss observed, which supports the further development of CT-388 for both obesity and type 2 diabetes. Dr. Garraway emphasized the therapy's potential for long-term weight reduction and glucose control, possibly making it a best-in-class treatment.

Obesity remains a critical global health challenge, linked to numerous comorbidities such as type 2 diabetes, cardiovascular diseases, and chronic kidney disease. Current estimates suggest that by 2035, over four billion people, or roughly half the world’s population, could be affected by obesity or being overweight. This escalating trend places a substantial burden on healthcare systems globally.

CT-388 is part of a class of incretin-based medications that aim to moderate blood sugar levels and reduce appetite. It selectively activates two receptors, GLP-1 and GIP, which play crucial roles in managing food intake and energy use. The dual targeting mechanism of CT-388 is believed to promote sustained weight loss and glucose reduction while maintaining a favorable safety profile.

The ongoing Phase Ib trial of CT-388 includes a multi-arm, multi-cohort design to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in overweight or obese adults, including those with type 2 diabetes. The primary focus is on safety and tolerability, with secondary endpoints examining the drug’s impact on body weight and glucose regulation.

In addition to the current 24-week study, Genentech plans to conduct further research. An additional cohort will evaluate CT-388's effects over a 12-week period in obese patients with type 2 diabetes, with results expected in the latter half of 2024.

CT-388’s design aims to maximize its activity on GLP-1 and GIP receptors while minimizing receptor desensitization, potentially leading to prolonged therapeutic effects. This feature positions it as a strong candidate for effective long-term treatment of obesity and type 2 diabetes.

For over four decades, Genentech has been at the forefront of biotechnology, creating innovative treatments for severe and life-threatening conditions. As part of the Roche Group, Genentech continues its commitment to advancing medical science from its headquarters in South San Francisco, California.