Genentech's CT-388 Cuts Weight 22.5% Versus Placebo in Phase 2 Obesity Trial

Genentech said on January 26 that its experimental weekly injection CT-388 produced placebo-adjusted weight loss of 22.5% at 48 weeks at the highest dose tested in a Phase 2 trial in people with obesity, according to the company's announcement. The results are company-reported topline data; Genentech, a member of the Roche Group, said the full results will be presented at an upcoming medical congress.

CT-388 is an investigational once-weekly dual GLP-1/GIP receptor agonist being developed for obesity, type 2 diabetes and other obesity-related conditions. Genentech said it was designed to activate both receptors with minimal recruitment of a protein called beta-arrestin, which the company expects to prolong the drug's activity.

The trial results

The trial, CT388-103, was a randomized, double-blind, placebo-controlled, dose-finding Phase 2 study in 469 adults with obesity, or with overweight and at least one weight-related condition, who did not have type 2 diabetes. It tested five dosing groups with different up-titration schemes, up to 24 mg once weekly. The primary endpoint was percent change in body weight from baseline to week 48.

At the 24 mg dose, the 22.5% placebo-adjusted figure is based on the efficacy estimand (p<0.001). Under the treatment-regimen estimand, a second way of analyzing the data, placebo-adjusted weight loss was 18.3% (p<0.001). Genentech said weight loss had not reached a plateau at 48 weeks and that there was a clear dose-response relationship.

At week 48 on the 24 mg dose, 95.7% of treated participants lost at least 5% of their body weight, 87% lost at least 10%, 47.8% lost at least 20% and 26.1% lost at least 30%, the company reported. Some 54% of participants on that dose had a body mass index below 30 at the end of the trial, compared with 13% on placebo. Among participants with prediabetes at baseline, 73% on the 24 mg dose reached normal blood glucose levels, against 7.5% on placebo.

Safety and Phase 3 plans

Most gastrointestinal adverse events were mild to moderate and generally consistent with the incretin class, Genentech said. Discontinuations due to adverse events were 5.9% across the CT-388 arms and 1.3% on placebo, and the company said no new or unexpected safety signals were seen.

"The robust weight loss combined with a well-tolerated safety profile reinforces our confidence in the clinical development program as we advance to Phase III trials," said Levi Garraway, Genentech's chief medical officer and head of global product development.

The Phase 3 program in obesity, called Enith1 and Enith2, is expected to start this quarter, according to the release. A separate Phase 2 study, CT388-104, is testing the drug in people with obesity or overweight who also have type 2 diabetes, and Genentech said it is considering CT-388 as a combination partner for another obesity candidate, petrelintide. Trade publication PMLiVE reported the trial's headline figures on January 29.