Genentech's dual GLP-1/GIP agonist enicepatide cuts HbA1c 2.65% and weight 15.5% at 48 weeks in Phase II T2D trial
核心洞察
Genentech reported positive topline Phase II results for enicepatide (搜索), a once-weekly dual GLP-1/GIP receptor (搜索) agonist, in adults with type 2 diabetes (搜索) and overweight or obesity (搜索).
At the 24 mg dose, enicepatide (搜索) reduced HbA1c by 2.65% and body weight by 15.5% at 48 weeks, meeting both dual primary endpoints.
Ninety percent of patients on 24 mg reached HbA1c of 6.5% or below and 62% achieved normoglycemia, while patients with baseline HbA1c above 8.5% saw a 4.13% reduction.
Genentech, a member of the Roche Group, reported 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 living with type 2 diabetes (搜索) (T2D) and overweight or obesity (搜索). The study met both dual primary endpoints, showing dose-dependent reductions in blood glucose and body weight at 48 weeks.
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 of patients 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 T2D, and 62% achieved normoglycemia, defined as HbA1c below 5.7%, restoring blood glucose to a non-diabetic range.
Weight loss without a plateau
The 24 mg enicepatide (搜索) arm recorded a mean weight loss of 15.5% at 48 weeks, with no demonstrable plateau at that timepoint.
"We are highly encouraged by the efficacy demonstrated by enicepatide (搜索) in this Phase II study, including the meaningful proportion of patients reaching normalized glucose levels within less than a year of treatment," said Levi Garraway, M.D., Ph.D., 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)."
Safety and tolerability
The safety and tolerability profile of enicepatide (搜索) was consistent with other established incretin-based therapies. The most common adverse events were predominantly mild-to-moderate gastrointestinal effects. Treatment discontinuation due to adverse events was low, at 2.0% across enicepatide arms versus 0.0% in the placebo arm, and no new safety signals were identified.
Trial design
CT-388-104 (NCT06628362) is a randomized, double-blind, placebo-controlled, parallel-group, multi-center Phase II trial evaluating the efficacy, safety, and tolerability of once-weekly subcutaneous enicepatide (搜索) administered for 48 weeks in 447 adults living with T2D and overweight or obesity (搜索). The dual primary outcomes were changes from baseline in HbA1c and body weight at week 48.
Mechanism and development plans
Enicepatide (搜索) is an investigational once-weekly subcutaneous injectable dually biased GLP-1/GIP receptor (搜索) agonist in development for obesity (搜索), type 2 diabetes (搜索), and additional cardiovascular indications. It is designed to activate both the GLP-1 and GIP receptors potently while causing minimal to no beta-arrestin recruitment at either receptor. According to Genentech, this biased signalling minimizes receptor internalization and consequent desensitization, which is expected to lead to prolonged pharmacological activity.
Genentech is advancing a late-stage development 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, Pharma. "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
Obesity (搜索) and T2D are described by Genentech as among the most urgent global public health challenges, with rising prevalence driving morbidity, disability, and premature death. Obesity is a major risk factor for T2D because excess body fat contributes to insulin resistance and dysfunction of insulin-producing cells; people living with obesity are seven times more likely to develop T2D than those with a normal body mass index.
Diabetes affects nearly 600 million adults worldwide, with T2D representing approximately 90% of cases and incidence rising fastest in low- and middle-income countries. Complications include blindness, kidney failure, strokes, and amputations. People living with diabetes face a 2 to 4 times higher risk of hypertension, heart failure, stroke, and coronary artery disease than those without it.