A phase 2 trial of Roche’s dual GLP-1/GIP receptor agonist has hit its primary endpoints, painting the drug candidate as a potential treatment for patients with both type 2 diabetes and obesity.
The molecule, enicepatide, is one of the assets that Roche acquired in its $2.7 billion takeover of Carmot Therapeutics. Also called CT-388, enicepatide hits the same targets as tirzepatide, the drug Eli Lilly sells as Mounjaro and Zepbound. But Roche has identified enicepatide’s dually biased mechanism as a point of difference, predicting that it will lead to prolonged pharmacological activity.
Having published weight-loss data in January, Roche followed up on Tuesday with results from another phase 2 trial. Unlike the earlier study, the latest trial included patients with type 2 diabetes, making it a key indicator of the injectable drug candidate’s prospects beyond obesity.
HbA1c, a measure of blood sugar, fell 2.65% in patients who received the top 24-mg dose of enicepatide weekly for 48 weeks. Roche framed the result as evidence of enicepatide’s best-in-disease potential.
Lilly reported (PDF) HbA1c reductions of up to 1.8% at Week 40 of its phase 3 Mounjaro trial. HbA1c fell up to 1.94% in patients who received retatrutide, Lilly’s investigational triple agonist, for 40 weeks in a phase 3 trial. Novo reported (PDF) a 1.6% decline at Week 30 of its phase 3 Ozempic study.
Other endpoints suggest enicepatide is at least as efficacious as the competition, although cross-trial comparisons can be unreliable. Notably, the fact Roche assessed its endpoints eight weeks later than Lilly prevents direct comparisons.
With that caveat, up to 90% of patients receiving enicepatide reached an HbA1c level of 6.5% or below, compared to up to 85% of people receiving retatrutide. The gap widened when looking at patients who had an HbA1c level of 5.7% or below, with 62% for enicepatide playing off against 46% for retatrutide.
Weight loss on enicepatide looks competitive too, reinforcing earlier findings from the obesity trial. At Week 48, mean weight loss in patients receiving the high dose of enicepatide was 15.5% “without a demonstrable plateau,” Roche said. The lack of a plateau suggests deeper weight loss will be possible in longer trials. Lilly reported Week 40 weight loss of up to 15.3% on retatrutide.
Roche has yet to share detailed safety and tolerability data. Consistent with other molecules in its class, enicepatide mostly caused mild-to-moderate gastrointestinal effects. Two percent of patients receiving the drug candidate discontinued because of adverse events, compared to 0% in the placebo group.
The data suggest enicepatide can hold its own against the competition. However, the earlier obesity data also painted enicepatide as competitive but failed to quell analyst doubts about Roche’s place in the market. Writing in a note to investors in July, BMO Capital Markets analysts suggested that, while enicepatide's weight loss was significant, “Lilly’s retatrutide is likely to remain the preferred high-efficacy weight loss agent at this time.”
Even so, Roche, which aspires to become a “top three” obesity company, is pushing ahead with a broad phase 3 program. The Swiss drugmaker is running a trio of late-stage enicepatide trials in obesity, two with global sites and one focused on China. Roche plans to start a phase 3 glycemic-control program and cardiovascular outcomes trials in the first half of next year.