Roche's CT-388 Achieves 22.5% Weight Loss in Phase 2 Trial
Roche's investigational dual GLP-1/GIP receptor agonist CT-388 demonstrated significant placebo-adjusted weight loss of 22.5% at 48 weeks without reaching a weight loss plateau in a Phase 2 clinical trial, the company announced this week. The results position the once-weekly injectable therapy as a potential competitor in the rapidly expanding obesity medication market.
Positive Phase 2 Trial Results
Once-weekly injections of CT-388 led to more than 95% of patients achieving a weight loss of more than 5% at 48 weeks, with more than a quarter achieving weight loss of 30%.
More than half of participants achieved resolution of obesity, compared to 13% in the placebo group. Additionally, 73% of patients who entered the trial with pre-diabetes saw normal blood glucose levels at week 48, compared to just 7.5% in the placebo group.
Trial Design and Data
The multi-center, randomized, double-blind, placebo-controlled, parallel group dose-finding Phase 2 trial was designed to evaluate the efficacy and safety of CT-388 at low, middle, and high doses in 469 people with obesity. Once-weekly subcutaneous injections of CT-388 were titrated up to 24 mg, representing the highest dose tested in the study.
CT-388 was designed to have potent activation of both GLP-1 and GIP receptors, but with minimal to no ß-arrestin recruitment on either receptor. This signaling minimizes desensitization, which is expected to lead to prolonged pharmacological activity.
Comparison to Other GLP-1/GIP Medications
William Blair's analysts declared that Roche's CT-388 appears comparable to Lilly's Zepbound, the current market leader in the dual GLP-1/GIP agonist class. Zepbound achieved about another 2% weight loss from week 48—the cut-off for Roche's data—and week 72. So CT-388's effect could grow in future readouts for the Phase 2 trial. CT-388 is also about a year behind a similar asset from Viking Therapeutics called VK2735, according to analysts.
Safety and Tolerability Profile
Just under 6% of patients on the treatment dropped out of the trial due to side effects, which Roche said were largely the gastrointestinal symptoms seen broadly with new weight loss treatments, versus 1.3% of those in the placebo group. The safety profile was generally consistent with other medications in the incretin drug class, with no new or unexpected safety signals reported.
Next Steps in Development
The Phase 3 clinical trial program of CT-388 in obesity (Enith1 and Enith2) is expected to start this quarter. Roche said the results, based on the highest of five doses tested, validate its choices on two larger Phase 3 trials it designed late last year.
CT-388 is currently being investigated in an additional Phase 2 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 type 2 diabetes. Since integrating CT-388 into the Roche pipeline, the company has designated it as a fast-track asset and significantly accelerated its clinical development to bring this potential therapy to patients.
Roche's Broader Obesity Strategy
CT-388 was acquired through Roche's $2.7 billion purchase of US biotech firm Carmot Therapeutics in 2023. Roche has six drug candidates in trials for the treatment of obesity and related conditions such as type 2 diabetes and hypertension, which could all be launched by 2030. It forecasts three of them could become blockbusters with annual sales of more than $1 billion.
The therapy is also being combined with petrelintide, Zealand Pharma's amylin analog that provides a different mechanism of action for weight loss from the already-approved GLP-1 class of medications. The aim is to offer a weight loss solution without the gastrointestinal side effects that have become well-known among patients taking GLP-1s. Roche and partner Zealand are expected to initiate a combo study of the medicines in the first half of this year.
Roche has costly ambitions to catch up with Lilly and Novo Nordisk in an obesity drug market some analysts say could reach $150 billion annually by the early 2030s.
