Roche's Enicepatide Hits Both Phase II Endpoints in Type 2 Diabetes, With 2.65% HbA1c Drop at 24 mg
核心洞察
Roche reported that once-weekly enicepatide (搜索) met both primary endpoints in the Phase II CT-388-104 trial, producing dose-dependent reductions in HbA1c and body weight at 48 weeks.
At the highest titrated 24 mg dose, patients achieved a mean HbA1c reduction of 2.65% and mean weight loss of 15.5% without a demonstrable plateau.
Ninety percent of patients in the 24 mg arm reached the type 2 diabetes (搜索) glycemic threshold of HbA1c 6.5% or below, and 62% achieved normoglycemia.
Roche announced positive topline results from the Phase II CT-388-104 trial of enicepatide (搜索) (CT-388), an investigational once-weekly dual GLP-1/GIP receptor (搜索) agonist, in adults with type 2 diabetes (搜索) and overweight or obesity (搜索). The study met both dual primary endpoints, showing dose-dependent and clinically meaningful reductions in blood glucose and body weight at 48 weeks.
The trial randomized 447 adults with type 2 diabetes (搜索) and overweight or obesity (搜索) to once-weekly subcutaneous enicepatide (搜索) or placebo for 48 weeks in a double-blind, placebo-controlled, parallel-group, multi-center design. The dual primary outcomes were change from baseline in HbA1c and body weight at week 48.
Glycemic Control at the Highest Dose
Patients receiving the highest titrated dose of 24 mg achieved a mean HbA1c reduction of 2.65% at 48 weeks from a baseline HbA1c of 8.1%. In the subgroup with poor baseline glycemic control (HbA1c above 8.5%), the 24 mg dose produced an HbA1c reduction of 4.13% at 48 weeks.
By week 48, 90% of patients in the 24 mg arm reached an HbA1c of 6.5% or below, the diagnostic threshold for type 2 diabetes (搜索), while 62% achieved normoglycemia, defined as HbA1c below 5.7%. Roche characterized the results as highlighting the molecule's potential for best-in-disease glycemic control.
Weight Loss Without a Plateau
The 24 mg enicepatide (搜索) arm recorded a mean weight loss of 15.5% at 48 weeks, which Roche reported occurred without a demonstrable plateau. The company described the reductions in both glucose and weight as dose-dependent across the study.
Safety and Tolerability
Enicepatide (搜索)'s safety and tolerability profile was consistent with other established incretin-based therapies, according to Roche. The most common adverse events were predominantly mild-to-moderate gastrointestinal effects, and no new safety signals were identified. Treatment discontinuation due to adverse events was low, at 2.0% across enicepatide arms versus 0.0% in the placebo arm.
"We are highly encouraged by the efficacy demonstrated by enicepatide (搜索) in this Phase II study, including the meaningful proportion of patients reaching normalised glucose levels within less than a year of treatment," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. "Combined with sustained weight loss, enicepatide offers a potential best-in-disease profile capable of reducing and preventing complications as well as enhancing metabolic health for people living with type 2 diabetes (搜索)."
A Dually Biased Mechanism
Enicepatide (搜索) is an investigational once-weekly subcutaneous injectable in development for obesity (搜索), type 2 diabetes (搜索) and additional cardiovascular indications. The molecule is designed to potently activate both the GLP-1 and GIP receptors while producing minimal to no beta-arrestin (搜索) recruitment at either receptor. According to Roche, this biased signaling significantly minimizes receptor internalization and consequent desensitization, which is expected to lead to prolonged pharmacological activity. The company describes enicepatide as a unique dually biased GLP-1/GIP receptor (搜索) agonist designed for potentially greater efficacy with a favorable safety profile.
Late-Stage Development Plans
Roche is advancing a broad late-stage program for enicepatide (搜索), including two ongoing Phase III studies in chronic weight management, ENITH-1 and ENITH-2. The company plans to initiate a Phase III glycemic-control program and cardiovascular outcomes trials in the first half of 2027.
"These results reinforce our confidence in enicepatide (搜索) and our ambition to rapidly advance its development for people living with obesity (搜索), diabetes, and cardiovascular disease," said Teresa Graham, Chief Executive Officer, Roche Pharmaceuticals. "As we expand into late-stage clinical studies and explore novel combinations, we are leveraging our integrated diagnostic and therapeutic expertise to build a competitive cardiometabolic portfolio, aiming to protect people from early metabolic dysfunction to advanced organ damage, ultimately reducing the global disease burden."
Disease Burden
Roche notes that obesity (搜索) and type 2 diabetes (搜索) are among the most urgent global public health challenges, with prevalence continuing to rise and driving morbidity, disability and premature death. People living with obesity are seven times more likely to develop type 2 diabetes than those with a normal body mass index. Diabetes affects nearly 600 million adults worldwide, with type 2 diabetes representing approximately 90% of cases and incidence rising fastest in low- and middle-income countries. People with diabetes face a two- to four-fold higher risk of hypertension, heart failure, stroke and coronary artery disease than those without the condition.