Genentech: enicepatide Phase II cuts HbA1c and weight in T2D with overweight/obesity
- Enicepatide 24 mg reduced mean HbA1c by 2.65% at 48 weeks (baseline 8.1%).
- In patients with baseline HbA1c >8.5%, 24 mg produced a 4.13% HbA1c reduction at 48 weeks.
- At week 48, 90% in the 24 mg arm reached ≤6.5% HbA1c and 62% achieved normoglycemia (<5.7%).
- Mean weight loss at 24 mg was 15.5% at 48 weeks; discontinuation for adverse events was 2.0% in enicepatide arms and most AEs were mild‑to‑moderate gastrointestinal.
Phase II efficacy
Genentech reported topline results from CT‑388‑104 (NCT06628362), a randomized, double‑blind, placebo‑controlled Phase II trial in 447 adults with type 2 diabetes and overweight or obesity testing once‑weekly enicepatide for 48 weeks. At the highest titrated dose (24 mg) mean HbA1c fell 2.65% from a baseline of 8.1% at week 48; in participants with baseline HbA1c >8.5% the reduction was 4.13%. By week 48, 90% of the 24 mg cohort reached ≤6.5% HbA1c and 62% achieved normoglycemia (<5.7%). Mean weight loss in the 24 mg arm was 15.5% at 48 weeks with no demonstrable plateau.
Safety and tolerability
Safety findings were consistent with established incretin‑based therapies. The most common adverse events were predominantly mild‑to‑moderate gastrointestinal events. Treatment discontinuation due to adverse events was low (2.0% in enicepatide arms; 0.0% in the placebo arm) and no new safety signals were identified in the topline report.
Molecule profile and development plans
Enicepatide is an investigational, dually biased GLP‑1/GIP receptor agonist designed to activate both receptors while minimizing β‑arrestin recruitment to limit receptor internalization and prolong activity. Genentech said it is advancing late‑stage development with two ongoing Phase III chronic weight‑management studies (ENITH‑1 and ENITH‑2) and plans to initiate a Phase III glycemic‑control programme and cardiovascular outcomes trials in the first half of 2027.
Source: Genentech